AURKA F31I Polymorphism and Breast Cancer Risk in BRCA1 and BRCA2 Mutation Carriers: A CIMBA study

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Couch, Fergus J.; Sinilnikova, Olga; Vierkant, Robert A; Pankratz, V. Shane; Fredericksen, Zachary S.; Stoppa-Lyonnet, Dominique; Coupier, Isabelle; Hughes, David; Hardouin, Agnès; Berthet, Pascaline; Peock, Susan; Cook, Margaret; Baynes, Caroline; Hodgson, Shirley; Morrison, Patrick J.; Porteous, Mary E.; Jakubowska, Anna; Lubinski, Jan; Gronwald, Jacek; Spurdle, Amanda B.; Schmutzler, Rita; Versmold, Beatrix; Engel, Christoph; Meindl, Alfons; Sutter, Christian; Horst, Jurgen; Schaefer, Dieter; Offit, Kenneth; Kirchhoff, Tomas; Andrulis, Irene L.; Ilyushik, Eduard; Glendon, Gordon; Devilee, Peter; Vreeswijk, Maaike P.G.; Vasen, Hans F.A.; Borg, Ake; Backenhorn, Katja; Struewing, Jeffery P.; Greene, Mark H.; Neuhausen, Susan L.; Rebbeck, Timothy R.; Nathanson, Katherine; Domchek, Susan; Wagner, Theresa; Garber, Judy E.; Szabo, Csilla; Zikan, Michal; Foretova, Lenka; Olson, Janet E.; Sellers, Thomas A.; Lindor, Noralane; Nevanlinna, Heli; Tommiska, Johanna; Aittomaki, Kristiina; Hamann, Ute; Rashid, Muhammad U.; Torres, Diana; Simard, Jacques; Durocher, Francine; Guenard, Frederic; Lynch, Henry T.; Isaacs, Claudine; Weitzel, Jeffrey; Olopade, Olufunmilayo I.; Narod, Steven; Daly, Mary B.; Godwin, Andrew K.; Tomlinson, Gail; Easton, Douglas F.; Chenevix-Trench, Georgia; Antoniouon, Antonis C.

2009-01-01

The AURKA oncogene is associated with abnormal chromosome segregation and aneuploidy and predisposition to cancer. Amplification of AURKA has been detected at higher frequency in tumors from BRCA1 and BRCA2 mutation carriers than in sporadic breast tumors, suggesting that overexpression of AURKA and inactivation of BRCA1 and BRCA2 co-operate during tumor development and progression. The F31I polymorphism in AURKA has been associated with breast cancer risk in the homozygous state in prior studies. We evaluated whether the AURKA F31I polymorphism modifies breast cancer risk in BRCA1 and BRCA2 mutation carriers from the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA). CIMBA was established to provide sufficient statistical power through increased numbers of mutation carriers to identify polymorphisms that act as modifiers of cancer risk and can refine breast cancer risk estimates in BRCA1 and BRCA2 mutation carriers. A total of 4935 BRCA1 and 2241 BRCA2 mutation carriers and 11 individuals carrying both BRCA1 and BRCA2 mutations were genotyped for F31I. Overall, homozygosity for the 31I allele was not significantly associated with breast cancer risk in BRCA1 and BRCA2 carriers combined (HR = 0.91; 95% CI 0.77-1.06). Similarly, no significant association was seen in BRCA1 (HR = 0.90; 95% CI 0.75-1.08) or BRCA2 carriers (HR = 0.93; 95% CI 0.67-1.29) or when assessing the modifying effects of either bilateral prophylactic oophorectomy or menopausal status of BRCA1 and BRCA2 carriers. In summary, the F31I polymorphism in AURKA is not associated with a modified risk of breast cancer in BRCA1 and BRCA2 carriers. PMID:17627006

Common HEXB polymorphisms reduce serum HexA and HexB enzymatic activities, potentially masking Tay-Sachs disease carrier identification.

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Vallance, Hilary; Morris, Tara J; Coulter-Mackie, Marion; Lim-Steele, Joyce; Kaback, Michael

2006-02-01

A DNA-proven Tay-Sachs disease (TSD) carrier and his brother were found to have serum percent Hexosaminidase A (%HexA) enzymatic activities in the non-carrier range, while the leukocyte %HexA profiles clearly identified them as TSD heterozygotes. Both their serum HexA and HexB enzymatic activities were below reference range, suggesting inheritance of mutations in both the HEXA (alpha-subunit) and HEXB (beta-subunit) genes. DNA sequencing revealed that both individuals, carried the common HEXA 1277_1278insTATC mutation, and two common HEXB polymorphisms: [619A>G (+) delTG]. To determine if these HEXB polymorphisms reduce HexA and HexB enzymatic activities, 69 DNA samples from subjects previously screened enzymatically in both serum and leukocytes for TSD carrier status were selected for either high, mid-range or low serum Total Hex (defined as the sum of HexA and HexB) activities and were tested for the HEXB mutations. Further, three additional TSD carriers ascertained by the atypical pattern of normal serum %HexA but carrier leukocyte %HexA, were found to have the [delTG (+) 619A>G] genotype. In addition, the frequency of the [delTG (+) 619A>G] genotype was significantly higher (P G] haplotype in the Ashkenazi Jewish population (approximately 10%), up to 10% of TSD carriers may have normal serum %HexA values with low total Hex. Accordingly, serum %HexA should not be the sole criterion used for carrier status determination. Where total Hex activity is reduced, further testing with leukocyte Hex profiles is indicated.

No differences in brain microstructure between young KIBRA-C carriers and non-carriers.

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Hu, Li; Xu, Qunxing; Li, Jizhen; Wang, Feifei; Xu, Xinghua; Sun, Zhiyuan; Ma, Xiangxing; Liu, Yong; Wang, Qing; Wang, Dawei

2018-01-02

KIBRA rs17070145 polymorphism is associated with variations in memory function and the microstructure of related brain areas. Diffusion kurtosis imaging (DKI) as an extension of diffusion tensor imaging that can provide more information about changes in microstructure, based on the idea that water diffusion in biological tissues is heterogeneous due to structural hindrance and restriction. We used DKI to explore the relationship between KIBRA gene polymorphism and brain microstructure in young adults. We recruited 100 healthy young volunteers, including 53 TT carriers and 47 C allele carriers. No differences were detected between the TT homozygotes and C-allele carriers for any diffusion and kurtosis parameter. These results indicate KIBRA rs17070145 polymorphism likely has little or no effect on brain microstructure in young adults.

Factor VII R353Q genetic polymorphism is associated with altered warfarin sensitivity among CYP2C9 *1/*1 carriers.

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Mlynarsky, Liat; Bejarano-Achache, Idit; Muszkat, Mordechai; Caraco, Yoseph

2012-05-01

Warfarin responsiveness is characterized by marked interindividual variability. A major portion of this variability is attributed to CYP2C9 and VKORC1 polymorphisms, but almost 50% is still unaccounted for. This paper reports the first prospective study on the association between factor VII R353Q polymorphism and warfarin responsiveness during induction. Genotyping for factor VII R353Q and 323D/I polymorphisms was performed in a cohort consisting of 374 patients (198 CYP2C9*1/*1) treated with warfarin who were prospectively followed from warfarin initiation. Compared with *1/*1-R/R and *1/*1-R/Q genotype carriers, *1/*1-Q/Q homozygotes achieved higher International Normalized Ratio (INR) values while consuming lower warfarin doses. The greater sensitivity was illustrated by 82.1% higher Warfarin Sensitivity Index During Induction (WSIDI) (0.14 ± 0.11 vs. 0.08 ± 0.50 mg⁻¹ Mann-Whitney, P = 0.043). Multiple regression analysis consisting of both genetic and nongenetic factors explained 26% of WSIDI variability, with R353Q genetic polymorphism having a modest yet significant effect and accounting for 1.7% of the overall variability. Moreover, the incidence of overanticoagulation (i.e., INR > 4) was 6.94-fold higher among *1/*1-Q/Q vs. *1/*1-R/R&R/Q carriers during warfarin induction (Pearson chi-square, P = 0.005). These findings were not accounted for by a chance difference in the distribution of VKORC1 genotypes. Analysis of these parameters among the entire cohort, including CYP2C9*2 and CYP2C9*3 variant allele carriers, did not reach statistical significance. Warfarin responsiveness during induction was unrelated to factor VII 323D/I genetic polymorphism. The response to warfarin during induction is influenced by factor VII R353Q polymorphism. The prospective use of this polymorphism, along with CYP2C9 and VKORC1, may enhance the accuracy of warfarin loading. However, the impact of R353Q polymorphism on overall warfarin response is subtle, and it is therefore

Influence of the MDM2 single nucleotide polymorphism SNP309 on tumour development in BRCA1 mutation carriers

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Johnson Peter W

2006-03-01

Full Text Available Abstract Background The MDM2 gene encodes a negative regulator of the p53 tumour suppressor protein. A single nucleotide polymorphism (SNP in the MDM2 promoter (a T to G exchange at nucleotide 309 has been reported to produce accelerated tumour formation in individuals with inherited p53 mutations. We have investigated the effect of the MDM2 SNP309 on clinical outcome in a cohort of patients with germline mutations of BRCA1. Methods Genomic DNA was obtained for 102 healthy controls and 116 patients with established pathogenic mutations of BRCA1 and Pyrosequencing technology™ was used to determine the genotype at the MDM2 SNP309 locus. Results The polymorphism was present in 52.9% of the controls (G/T in 37.3% and G/G in 15.6% and 58.6% of the BRCA1 mutation carriers (47.4% G/T and 11.2% G/G. Incidence of malignancy in female BRCA1 carriers was not significantly higher in SNP309 carriers than in wildtype (T/T individuals (72.7% vs. 75.6%, p = 1.00. Mean age of diagnosis of first breast cancer was 41.2 years in the SNP309 G/G genotype carriers, 38.6 years in those with the SNP309 G/T genotype and 39.0 years in wildtype subjects (p = 0.80. Conclusion We found no evidence that the MDM2 SNP309 accelerates tumour development in carriers of known pathogenic germline mutations of BRCA1.

Haplotype analysis of TP53 polymorphisms, Arg72Pro and Ins16, in BRCA1 and BRCA2 mutation carriers of French Canadian descent

International Nuclear Information System (INIS)

Cavallone, Luca; Arcand, Suzanna L; Maugard, Christine; Ghadirian, Parviz; Mes-Masson, Anne-Marie; Provencher, Diane; Tonin, Patricia N

2008-01-01

The TP53 polymorphisms Arg72Pro (Ex4+199 G>C) and Ins16 (IVS3+24 ins16) have been proposed to modify risk of breast cancer associated with germline BRCA1 and BRCA2 mutations. Allele frequencies of these polymorphisms were investigated to determine if they modify risk in BRCA mutation carriers in breast cancer cases drawn from French Canadian cancer families, a population shown to exhibit strong founder effects. The frequencies of the TP53 alleles, genotypes and haplotypes of 157 index breast cancer cases comprised of 42 BRCA1 mutation carriers, 57 BRCA2 mutation carriers, and 58 BRCA mutation-negative cases, where each case was drawn from independently ascertained families were compared. The effect of TP53 variants on the age of diagnosis was also investigated for these groups. The TP53 polymorphisms were also investigated in 112 women of French Canadian descent with no personal history of cancer. The BRCA mutation-positive groups had the highest frequency of homozygous carriers of the 72Pro allele compared with mutation-negative group. The TP53 polymorphisms exhibited linkage disequilibrium (p < 0.001), where the 72Arg and Ins16minus alleles occurred in strong disequilibrium. The highest frequency of carriers of Ins16minus-72Arg haplotype occurred in the BRCA mutation-negative groups. The BRCA1 mutation carriers homozygous for the 72Pro allele had the youngest ages of diagnosis of breast cancer. However none of these observations were statistically significant. In contrast, the BRCA2 mutation carriers homozygous for the 72Pro allele had a significantly older age of diagnosis of breast cancer (p = 0.018). Moreover, in this group, the mean age of diagnosis of breast cancer in carriers of the Ins16minus-72Arg haplotype was significantly younger than that of the individuals who did not this carry this haplotype (p = 0.009). We observed no significant association of breast cancer risk with TP53 genetic variants based on BRCA1/2 mutation carrier status. Although the

Lower baseline performance but greater plasticity of working memory for carriers of the val allele of the COMT Val¹⁵⁸Met polymorphism.

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Bellander, Martin; Bäckman, Lars; Liu, Tian; Schjeide, Brit-Maren M; Bertram, Lars; Schmiedek, Florian; Lindenberger, Ulman; Lövdén, Martin

2015-03-01

Little is known about genetic contributions to individual differences in cognitive plasticity. Given that the neurotransmitter dopamine is critical for cognition and associated with cognitive plasticity, we investigated the effects of 3 polymorphisms of dopamine-related genes (LMX1A, DRD2, COMT) on baseline performance and plasticity of working memory (WM), perceptual speed, and reasoning. One hundred one younger and 103 older adults underwent approximately 100 days of cognitive training, and extensive testing before and after training. We analyzed the baseline and posttest data using latent change score models. For working memory, carriers of the val allele of the COMT polymorphism had lower baseline performance and larger performance gains from training than carriers of the met allele. There was no significant effect of the other genes or on other cognitive domains. We relate this result to available evidence indicating that met carriers perform better than val carriers in WM tasks taxing maintenance, whereas val carriers perform better at updating tasks. We suggest that val carriers may show larger training gains because updating operations carry greater potential for plasticity than maintenance operations. PsycINFO Database Record (c) 2015 APA, all rights reserved.

Genotypic carriers of the obesity-associated FTO polymorphism exhibit different cardiometabolic profiles after an intervention

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GREICE G. MORAES

Full Text Available ABSTRACT Background: Children and adolescents with at-risk genotypes (AA/AT of the rs9939609 polymorphism in FTO, a fat mass and obesity-associated gene, may exhibit different cardiometabolic profile responses than subjects with the TT genotype after an interdisciplinary intervention. Methods: The sample consisted of 36 school children from southern Brazil. We used DNA quantitation and real-time polymerase chain reaction (PCR for polymorphism genotyping. We measured anthropometric parameters (body mass index (BMI, waist circumference, hip circumference, waist-hip ratio, body fat percentage and skinfold sum, biochemical parameters (glucose, lipid profile, ultra-sensitive C-reactive protein, uric acid, alanine aminotransferase, aspartate aminotransferase, insulin and adiponectin and blood pressure. The 4-month intervention consisted of physical education classes, nutritional counseling, and postural and oral health counseling. Results: We observed no significant differences among the groups (AA, AT and TT after the intervention. However, we observed improvements in three parameters (waist circumference, hip circumference and C-reactive protein in the AT/AA genotype group and in two parameters (hip circumference and uric acid in the TT genotype group. Conclusions: After an intervention program, carriers of at-risk genotypes for obesity (AA/AT do not exhibit differences in biochemical parameters, blood pressure and anthropometric parameters compared with carriers of the TT genotype.

Correlation of reversion-inducing cysteine-rich protein with kazal motifs (RECK) and extracellular matrix metalloproteinase inducer (EMMPRIN), with MMP-2, MMP-9, and survival in colorectal cancer.

NARCIS (Netherlands)

Jagt, M. van der; Sweep, C.G.J.; Waas, E.T.; Hendriks, T.; Ruers, T.J.M.; Merry, A.H.; Wobbes, Th.; Span, P.N.

2006-01-01

mRNA, and latent and active levels MMP-2 and -9 were higher in tumor tissue compared to normal tissue from 63 patients with colorectal cancer, whereas RECK and EMMPRIN levels were lower. Correlations between mRNA, latent, and active MMP were particular high for MMP-2 in tumor tissue (R(s)=0.6-0.8,

Application of GP IIIa gene Taq I polymorphism to determination of carrier status in Glanzmann's thrombasthenia families of Chinese origin

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Ruan Changgeng; Gu Jianmin; Wang Xiaodong; Chu Xiaohong; Pan Junliang; Wu Qingyu

1992-08-01

Glanzmann's thrombasthenia is a bleeding disorder caused by qualitative and/or quantitative defects of platelet membrane glycoprotein (GP) Ii b /III a complex. The disease is inherited in an autosomal recessive manner. The use of cDNA probes to study restriction fragment length polymorphisms (RFLPs) in GPIII a gene is reported. A Taq I polymorphism was identified and this RFLP consisted of variant bands of 6.5 kb/4.0 and 2.5 kb with a frequency of 0.46/0.54 in Chinese population. The Taq I polymorphism was further localized by polymerase chain reaction (PCR) method to exon VIII of the GPIII a gene. In two Glanzmann's thrombasthenia families, the Taq I RFLP studied with both Southern blotting and PCR methods identified defective GPIII a gene inherited by patients, and determined the genotype of asymptomatic subjects. Analysis of this Taq I polymorphism by PCR method should be potentially useful in future for the carrier detection and prenatal diagnosis in Glanzmann's thrombasthenia families

Association of the solute carrier family 11 member 1 gene polymorphisms with susceptibility to leprosy in a Brazilian sample

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Maria José Franco Brochado

2016-02-01

Full Text Available Natural resistance-associated macrophage protein 1/solute carrier family 11 member 1 gene (Nramp1/Slc11a1 is a gene that controls the susceptibility of inbred mice to intracellular pathogens. Polymorphisms in the human Slc11a1/Nramp1 gene have been associated with host susceptibility to leprosy. This study has evaluated nine polymorphisms of the Slc11a1/Nramp1 gene [(GTn, 274C/T, 469+14G/C, 577-18G/A, 823C/T, 1029 C/T, 1465-85G/A, 1703G/A, and 1729+55del4] in 86 leprosy patients (67 and 19 patients had the multibacillary and the paucibacillary clinical forms of the disease, respectively, and 239 healthy controls matched by age, gender, and ethnicity. The frequency of allele 2 of the (GTn polymorphism was higher in leprosy patients [p = 0.04, odds ratio (OR = 1.49], whereas the frequency of allele 3 was higher in the control group (p = 0.03; OR = 0.66. Patients carrying the 274T allele (p = 0.04; OR = 1.49 and TT homozygosis (p = 0.02; OR = 2.46, such as the 469+14C allele (p = 0.03; OR = 1.53 of the 274C/T and 469+14G/C polymorphisms, respectively, were more frequent in the leprosy group. The leprosy and control groups had similar frequency of the 577-18G/A, 823C/T, 1029C/T, 1465-85G/A, 1703G/A, and 1729+55del4 polymorphisms. The 274C/T polymorphism in exon 3 and the 469+14G/C polymorphism in intron 4 were associated with susceptibility to leprosy, while the allele 2 and 3 of the (GTn polymorphism in the promoter region were associated with susceptibility and protection to leprosy, respectively.

Stability and carrier transport properties of phosphorene-based polymorphic nanoribbons

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Kaur, Sumandeep; Kumar, Ashok; Srivastava, Sunita; Pandey, Ravindra; Tankeshwar, K.

2018-04-01

Few-layer black phosphorene has recently attracted significant interest in the scientific community. In this paper, we consider several polymorphs of phosphorene nanoribbons (PNRs) and employ deformation potential theory within the effective mass approximation, together with density functional theory, to investigate their structural, mechanical and electronic properties. The results show that the stability of a PNR strongly depends on the direction along which it can be cut from its 2D counterpart. PNRs also exhibit a wide range of line stiffnesses ranging from 6 × 1010 eV m-1 to 18 × 1011 eV m-1, which has little dependence on the edge passivation. Likewise, the calculated electronic properties of PNRs show them to be either a narrow-gap semiconductor (E g 1 eV). The carrier mobility of PNRs is found to be comparable to that of black phosphorene. Some of the PNRs show an n-type (p-type) semiconducting character owing to their higher electron (hole) mobility. Passivation of the edges leads to n-type ↔ p-type transition in many of the PNRs considered. The predicted novel characteristics of PNRs, with a wide range of mechanical and electronic properties, make them potentially suitable for use in nanoscale devices.

Preimplantation genetic haplotyping a new application for diagnosis of translocation carrier's embryos- preliminary observations of two robertsonian translocation carrier families.

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Shamash, Jana; Rienstein, Shlomit; Wolf-Reznik, Haike; Pras, Elon; Dekel, Michal; Litmanovitch, Talia; Brengauz, Masha; Goldman, Boleslav; Yonath, Hagith; Dor, Jehoshua; Levron, Jacob; Aviram-Goldring, Ayala

2011-01-01

Preimplantation genetic diagnosis using fluorescence in-situ hybridization (PGD-FISH) is currently the most common reproductive solution for translocation carriers. However, this technique usually does not differentiate between embryos carrying the balanced form of the translocation and those carrying the homologous normal chromosomes. We developed a new application of preimplantation genetic haplotyping (PGH) that can identify and distinguish between all forms of the translocation status in cleavage stage embryos prior to implantation. Polymorphic markers were used to identify and differentiate between the alleles that carry the translocation and those that are the normal homologous chromosomes. Embryos from two families of robertsonian translocation carriers were successfully analyzed using polymorphic markers haplotyping. Our preliminary results indicate that the PGH is capable of distinguishing between normal, balanced and unbalanced translocation carrier embryos. This method will improve PGD and will enable translocation carriers to avoid transmission of the translocation and the associated medical complications to offspring.

Preproghrelin Leu72Met polymorphism in obese Korean children.

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Jo, Dae-Sun; Kim, Se-Lim; Kim, Sun-Young; Hwang, Pyoung Han; Lee, Kee-Hyoung; Lee, Dae-Yeol

2005-11-01

Ghrelin is a novel gut-brain peptide that has somatotropic, orexigenic, and adipogenic effects. We examined the preproghrelin Leu72Met polymorphism in 222 obese Korean children to determine whether it is associated with obesity. The frequencies of the Leu72Met polymorphism were 29.3% in obese, 32.3% in overweight, and 32.5% in lean Korean children. No significant difference was found between Met72 carrier and non-carrier obese children with respect to BMI, total body fat, serum triglycerides, total cholesterol, or LDL-cholesterol levels. Our data suggest that the preproghrelin Leu72Met polymorphism is not associated with obesity in children.

Association of TMEM106B gene polymorphism with age at onset in granulin mutation carriers and plasma granulin protein levels.

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Cruchaga, Carlos; Graff, Caroline; Chiang, Huei-Hsin; Wang, Jun; Hinrichs, Anthony L; Spiegel, Noah; Bertelsen, Sarah; Mayo, Kevin; Norton, Joanne B; Morris, John C; Goate, Alison

2011-05-01

To test whether rs1990622 (TMEM106B) is associated with age at onset (AAO) in granulin (GRN) mutation carriers and with plasma GRN levels in mutation carriers and healthy, elderly individuals. Rs1990622 (TMEM106B) was identified as a risk factor for frontotemporal lobar degeneration with TAR DNA-binding protein inclusions (FTLD-TDP) in a recent genome-wide association. Rs1990622 was genotyped in GRN mutation carriers and tested for association with AAO using the Kaplan-Meier method and a Cox proportional hazards model. Alzheimer's Disease Research Center. Subjects  We analyzed 50 affected and unaffected GRN mutation carriers from 4 previously reported FTLD-TDP families (HDDD1, FD1, HDDD2, and the Karolinska family). The GRN plasma levels were also measured in 73 healthy, elderly individuals. Age at onset and GRN plasma levels. The risk allele of rs1990622 was associated with a mean decrease of the AAO of 13 years (P = 9.9 × 10(-7)) and with lower plasma GRN levels in both healthy older adults (P = 4 × 10(-4)) and GRN mutation carriers (P = .0027). Analysis of the HapMap database identified a nonsynonymous single-nucleotide polymorphism rs3173615 (T185S) in perfect linkage disequilibrium with rs1990622. The association of rs1990622 with AAO explains, in part, the wide range in the AAO of disease among GRN mutation carriers. We hypothesize that rs1990622 or another variant in linkage disequilibrium could act in a manner similar to APOE in Alzheimer disease, increasing risk for disease in the general population and modifying AAO in mutation carriers. Our results also suggest that genetic variation in TMEM106B may influence risk for FTLD-TDP by modulating secreted levels of GRN.

TMEM106B gene polymorphism is associated with age at onset in granulin mutation carriers and plasma granulin protein levels

Science.gov (United States)

Cruchaga, Carlos; Graff, Caroline; Chiang, Huei-Hsin; Wang, Jun; Hinrichs, Anthony L.; Spiegel, Noah; Bertelsen, Sarah; Mayo, Kevin; Norton, Joanne B.; Morris, John C.; Goate, Alison

2011-01-01

Objective A recent genome-wide association study for frontotemporal lobar degeneration with TAR DNA-binding protein inclusions (FTLD-TDP), identified rs1990622 (TMEM106B) as a risk factor for FTLD-TDP. In this study we tested whether rs1990622 is associated with age at onset (AAO) in granulin (GRN) mutation carriers and with plasma GRN levels in mutation carriers and healthy elderly individuals. Design Rs1990622 was genotyped in GRN mutation carriers and tested for association with AAO using the Kaplan-Meier and a Cox proportional hazards model. Subjects We analyzed 50 affected and unaffected GRN mutation carriers from four previously reported FTLD-TDP families (HDDD1, FD1, HDDD2 and the Karolinska family). GRN plasma levels were also measured in 73 healthy, elderly individuals. Results The risk allele of rs1990622 is associated with a mean decrease of the age at onset of thirteen years (p=9.9×10−7), with lower plasma granulin levels in both healthy older adults (p = 4×10−4) and GRN mutation carriers (p=0.0027). Analysis of the HAPMAP database identified a non-synonymous single nucleotide polymorphism, rs3173615 (T185S) in perfect linkage disequilibrium with rs1990622. Conclusions The association of rs1990622 with AAO explains, in part, the wide range in the age at onset of disease among GRN mutation carriers. We hypothesize that rs1990622 or another variant in linkage disequilibrium could act in a manner similar to APOE in Alzheimer’s disease, increasing risk for disease in the general population and modifying AAO in mutation carriers. Our results also suggest that genetic variation in TMEM106B may influence risk for FTLD-TDP by modulating secreted levels of GRN. PMID:21220649

Efficacy of DNA double-strand breaks repair in breast cancer is decreased in carriers of the variant allele of the UBC9 gene c.73G>A polymorphism

International Nuclear Information System (INIS)

Synowiec, Ewelina; Krupa, Renata; Morawiec, Zbigniew; Wasylecka, Maja; Dziki, Lukasz; Morawiec, Jan; Blasiak, Janusz; Wozniak, Katarzyna

2010-01-01

UBC9 (E2) SUMO conjugating enzyme plays an important role in the maintenance of genome stability and integrity. In the present work we examined the association between the c.73G>A (Val25Met) polymorphism of the UBC9 gene (rs11553473) and efficacy of DNA double-strand breaks (DSBs) repair (DRE) in breast cancer patients. We determined the level of endogenous (basal) and exogenous (induced by γ-irradiation) DSBs and efficacy of their repair in peripheral blood lymphocytes of 57 breast cancer patients and 70 healthy individuals. DNA damage and repair were studied by neutral comet assay. Genotypes were determined in DNA from peripheral blood lymphocytes by allele-specific PCR (ASO-PCR). We also correlated genotypes with the clinical characteristics of breast cancer patients. We observed a strong association between breast cancer occurrence and the variant allele carried genotypes in patients with elevated level of basal as well as induced DNA damage (OR 6.74, 95% CI 2.27-20.0 and OR 5.33, 95% CI 1.81-15.7, respectively). We also found statistically significant (p A polymorphism of the UBC9 gene in breast cancer patients. Carriers of variant allele have decreased DNA DRE as compared to wild type genotype carriers. We did not find any association with the UBC9 gene polymorphism and estrogen and progesterone receptor status. The variant allele of the UBC9 gene polymorphism was strongly inversely related to HER negative breast cancer patients (OR 0.03, 95% CI 0.00-0.23). Our results suggest that the c.73G>A polymorphism of the UBC9 gene may affect DNA DSBs repair efficacy in breast cancer patients.

Efficacy of DNA double-strand breaks repair in breast cancer is decreased in carriers of the variant allele of the UBC9 gene c.73G>A polymorphism

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Synowiec, Ewelina [Department of Molecular Genetics, University of Lodz, Lodz (Poland); Krupa, Renata [Laboratory of DNA Repair, Department of Molecular Genetics, University of Lodz, Banacha 12/16, Lodz (Poland); Morawiec, Zbigniew; Wasylecka, Maja [Department of Surgical Oncology, N. Copernicus Hospital, Lodz (Poland); Dziki, Lukasz; Morawiec, Jan [Department of General and Colorectal Surgery, Medical University of Lodz, Lodz (Poland); Blasiak, Janusz [Department of Molecular Genetics, University of Lodz, Lodz (Poland); Wozniak, Katarzyna, E-mail: wozniak@biol.uni.lodz.pl [Laboratory of DNA Repair, Department of Molecular Genetics, University of Lodz, Banacha 12/16, Lodz (Poland)

2010-12-10

UBC9 (E2) SUMO conjugating enzyme plays an important role in the maintenance of genome stability and integrity. In the present work we examined the association between the c.73G>A (Val25Met) polymorphism of the UBC9 gene (rs11553473) and efficacy of DNA double-strand breaks (DSBs) repair (DRE) in breast cancer patients. We determined the level of endogenous (basal) and exogenous (induced by {gamma}-irradiation) DSBs and efficacy of their repair in peripheral blood lymphocytes of 57 breast cancer patients and 70 healthy individuals. DNA damage and repair were studied by neutral comet assay. Genotypes were determined in DNA from peripheral blood lymphocytes by allele-specific PCR (ASO-PCR). We also correlated genotypes with the clinical characteristics of breast cancer patients. We observed a strong association between breast cancer occurrence and the variant allele carried genotypes in patients with elevated level of basal as well as induced DNA damage (OR 6.74, 95% CI 2.27-20.0 and OR 5.33, 95% CI 1.81-15.7, respectively). We also found statistically significant (p < 0.05) difference in DRE related to the c.73G>A polymorphism of the UBC9 gene in breast cancer patients. Carriers of variant allele have decreased DNA DRE as compared to wild type genotype carriers. We did not find any association with the UBC9 gene polymorphism and estrogen and progesterone receptor status. The variant allele of the UBC9 gene polymorphism was strongly inversely related to HER negative breast cancer patients (OR 0.03, 95% CI 0.00-0.23). Our results suggest that the c.73G>A polymorphism of the UBC9 gene may affect DNA DSBs repair efficacy in breast cancer patients.

Preproghrelin Leu72Met polymorphism predicts a lower rate of developing renal dysfunction in type 2 diabetic nephropathy.

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Lee, Dae-Yeol; Kim, Sun-Young; Jo, Dae-Sun; Hwang, Pyoung Han; Kang, Kyung Pyo; Lee, Sik; Kim, Won; Park, Sung Kwang

2006-07-01

Ghrelin is a novel peptide hormone, which exerts somatotropic, orexigenic and adipogenic effects. Recent studies have shown that the preproghrelin Leu72Met polymorphism is associated with serum creatinine (Scr) concentration in type 2 diabetes; 72Met carriers exhibited lower Scr levels as compared with the 72Met non-carriers. We hypothesized that the preproghrelin Leu72Met polymorphism is associated with a lower rate of developing renal dysfunction in patients with type 2 diabetic nephropathy. The preproghrelin Leu72Met polymorphism was investigated using PCR techniques in 138 patients with diabetic nephropathy divided into two groups, one with normal renal function and the other with renal dysfunction. Determination of the frequency of the preproghrelin Leu72Met polymorphism was the main outcome measure. The frequency of the Leu72Met polymorphism in diabetic nephropathy was significantly lower in patients with renal dysfunction (15.9%, P polymorphism was also associated with serum total cholesterol levels in diabetic nephropathy patients with renal dysfunction; the 72Met carriers had lower total cholesterol levels than the 72Met non-carriers (P < 0.05). These data suggest that 72Met carrier status may be used as a marker predicting a lower chance of developing renal dysfunction in diabetic nephropathy.

Obesity-related gene ADRB2, ADRB3 and GHRL polymorphisms and the response to a weight loss diet intervention in adult women.

Science.gov (United States)

Saliba, Louise F; Reis, Rodrigo S; Brownson, Ross C; Hino, Adriano A; Tureck, Luciane V; Valko, Cheryl; de Souza, Ricardo L R; Furtado-Alle, Lupe

2014-03-01

The individual response to diet may be influenced by gene polymorphisms. This study hypothesized that ADRB2 (Gln27Glu, rs1042714 and Arg16Gly, rs1042713), ADRB3 (Trp64Arg, rs4994) and GHRL (Leu72Met, rs696217) polymorphisms moderate weight loss. The study was a seven weeks dietary weight loss intervention with Brazilian adult obese women (n = 109). The body mass index (BMI) was calculated and polymorphisms in these genes were assessed by real-time PCR assays. Two-way repeated-measures ANOVA (2 × 2) were used to analyze the intervention effect between polymorphisms and BMI over the period and after stratification for age and socioeconomic status (SES). The weight loss intervention resulted in decreased BMI over the seven-week period (p polymorphism carriers and non-carriers, and although, the ADRB2, ADRB3 and GHRL polymorphisms did not moderate weight loss, the Gln27Glu polymorphism carriers showed a lower BMI compared to non-carriers in the low SES (p = 0.018) and the 30-39 y (p = 0.036) groups, suggesting a role for this polymorphism related to BMI control.

Unsupportive social interactions and affective states: examining associations of two oxytocin-related polymorphisms.

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McInnis, Opal A; McQuaid, Robyn J; Matheson, Kimberly; Anisman, Hymie

2017-01-01

Two single-nucleotide polymorphisms (SNPs) on oxytocin-related genes, specifically the oxytocin receptor (OXTR) rs53576 and the CD38 rs3796863 variants, have been associated with alterations in prosocial behaviors. A cross-sectional study was conducted among undergraduate students (N = 476) to examine associations between the OXTR and CD38 polymorphisms and unsupportive social interactions and mood states. Results revealed no association between perceived levels of unsupportive social interactions and the OXTR polymorphism. However, A carriers of the CD38 polymorphism, a variant previously associated with elevated oxytocin, reported greater perceived peer unsupportive interactions compared to CC carriers. As expected, perceived unsupportive interactions from peers was associated with greater negative affect, which was moderated by the CD38 polymorphism. Specifically, this relation was stronger among CC carriers of the CD38 polymorphism (a variant thought to be linked to lower oxytocin). When examining whether the OXTR polymorphism moderated the relation between unsupportive social interactions from peers and negative affect there was a trend toward significance, however, this did not withstand multiple testing corrections. These findings are consistent with the perspective that a variant on an oxytocin polymorphism that may be tied to lower oxytocin is related to poor mood outcomes in association with negative social interactions. At the same time, having a genetic constitution presumed to be associated with higher oxytocin was related to increased perceptions of unsupportive social interactions. These seemingly paradoxical findings could be related to previous reports in which variants associated with prosocial behaviors were also tied to relatively more effective coping styles to deal with challenges.

Comparison of CYP2C9, CYP2C19, CYP2D6, ABCB1, and SLCO1B1 gene-polymorphism frequency in Russian and Nanai populations

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Sychev DA

2017-03-01

Full Text Available Dmitrij Alekseevitch Sychev,1 Grigorij Nikolaevich Shuev,1 Salavat Shejhovich Suleymanov,2 Kristina Anatol’evna Ryzhikova,3 Karin Badavievich Mirzaev,3 Elena Anatol’evna Grishina,3 Natalia Evgenievna Snalina,3 Zhannet Alimovna Sozaeva,3 Anton Mikhailovich Grabuzdov,4 Irina Andreevna Matsneva4 1Department of Internal Medicine and Clinical Pharmacology, Russian Medical Academy of Continuing Professional Education, Ministry of Healthcare, Moscow, 2Saiko Russian–Japanese Medical Center, Khabarovsk, 3Research Centre, Russian Medical Academy of Continuous Professional Education, Ministry of Healthcare, 4Department of General Medicine, Sechenov First Moscow State Medical University, Moscow, Russian Federation Background: The efficiency and safety of drug therapy depends on the peculiarities of functioning of the P450 cytochrome group and transporting proteins. There are significant differences for single-nucleotide polymorphism (SNP frequency. Materials and methods: We studied the peculiarities of P450 cytochrome polymorphisms, SLCO1B1 transporting protein, and P-glycoprotein carriage in healthy volunteers in the Nanai ethnic group living in Russia, and compared them to the carriage of SNPs in the Russian population according to literature data. Results: After performing the real-time polymerase chain reactions on the samples from 70 healthy volunteers from the Nanai group, for the CYP2C9*2C430T polymorphism we determined 70 CC-genotype carriers. As for the CYP2C9*3A1075C polymorphism, we found 62 AA-genotype carriers and eight AC-genotype carriers. For the CYP2C19*2G681A polymorphism, we determined 39 GG-genotype carriers and 28 GA-genotype carriers, for the CYP2C19*3G636A polymorphism 58 GG-genotype carriers and 12 GA-genotype carriers, and for the CYP2C19*17C806T polymorphism 67 CC-genotype carriers and three CT-genotype carriers. For the CYP2D6*4G1846A polymorphism, the GG genotype had 68 carriers, and the GA genotype two carriers. For the

Influence of Interleukin-6 (174G/C Gene Polymorphism on Obesity in Egyptian Children

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Ola M. Ibrahim

2017-10-01

CONCLUSION: Our study showed that carriers of the C allele for the IL-6 (174G/C polymorphism have higher BMI. As the G174C polymorphism is likely to affect IL-6 expression and its physiological regulation; consequently this polymorphism may affect adiposity.

Association between promoter polymorphisms of OPN gene and cancer risk: a meta-analysis

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Liu JW

2015-12-01

Full Text Available Jingwei Liu,1–2 Caiyun He,1–2 Quan Yuan,1–2 Zhenning Wang,1–2 Chengzhong Xing,1–2 Yuan Yuan1–2 1Tumor Etiology and Screening Department of Cancer Institute and General Surgery, The First Affiliated Hospital of China Medical University, 2Key Laboratory of Cancer Etiology and Prevention, China Medical University, Liaoning Provincial Education Department, Shenyang, People’s Republic of China Background: Results of the association between polymorphisms of osteopontin (OPN gene promoter region and risk of cancer were inconclusive. The aim of this meta-analysis was to elucidate whether OPN promoter polymorphisms were associated with cancer risk.Methods: Electronic databases including PubMed, Web of Science, and Chinese National Knowledge Infrastructure were systematically searched. Odd ratios (ORs and their 95% confidential interval (CI were used to assess the strength of association between OPN promoter polymorphisms and cancer risks.Results: Nine studies were finally included in this meta-analysis. For OPN rs17524488 polymorphism, carriers of GG or -/G genotype were significantly associated with increased cancer risk compared with wild-type -/- carriers, respectively (GG vs -/-: OR =1.40, 95% CI =1.03–1.91, P=0.033; -/G vs -/-: OR =1.22, 95% CI =1.07–1.40, P=0.002. Additionally, G allele was significantly associated with increased cancer risk compared with (- allele (OR =1.21, 95% CI =1.04–1.40, P=0.016. However, no significant association was observed of OPN rs11730582 polymorphism and cancer risk (CC vs TT: OR =0.98, 95% CI =0.49–1.97, P=0.964; CT vs TT: OR =0.88, 95% CI =0.54–1.43, P=0.610.Conclusion: Carriers of GG or -/G genotype of OPN promoter rs17524488 (-156-/G polymorphism might be associated with increased risk of cancer compared with wild-type -/- carriers, respectively. However, no significant association was observed between OPN promoter rs11730582 (-443C/T polymorphism and risk of cancer. Keywords: OPN

FEATURES OF THE CLINICAL SIGNIFICANCE OF POLYMORPHIC VARIANTS OF ENOS AND AGTR2 GENES IN PATIENTS WITH CAD

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A. L. Khokhlov

2016-01-01

Full Text Available Coronary heart disease (CHD is a major cause of mortality. Morphological substrate of CHD in most cases is atherosclerosis, which is based on structural genes polymorphism eNOS and AGTR2. The aim of the study was to study the prevalence of eNOS and AGTR2 genes in patients with coronary artery disease and the association of these genes with coronary heart disease. The study involved 187 patients aged 36 to 86 years (62,2±11,2 with different forms of CHD: stable and unstable angina, myocardial infarction and 45 people without CHD. Determination of gene polymorphisms was performed by real-time PCR analyzer of nucleic acids IQ 5 Bio-Rad. Statistical analysis was performed using Statistica 10.0. The study revealed a significant difference between the incidence of homozygous AA allelic variant gene AGTR2 group of patients with myocardial infarction and the comparison group; polymorphic variant AA AGTR2 gene is associated with earlier onset of coronary artery disease; It found that carriers of the polymorphic variant gene GA AGTR2 beginning statistically CHD occurred significantly later than in carriers of alleles GG and AA; age CHD debut TT allele carriers of the eNOS gene is associated with an earlier onset of the disease and statistically significantly different from the age of first CHD in carriers of alleles of polymorphic variants of GG and GT; revealed a positive correlation between the polymorphic allele AGTR2 gene with the presence of arterial hypertension in patients with coronary artery disease; It determined that the T allele carriers of the polymorphic gene eNOS is associated more early onset of hypertension, found the association of the polymorphic allele gene AGTR2 the need to use higher doses of ACE inhibitor — perindopril.

Silencing of reversion-inducing cysteine-rich protein with Kazal motifs stimulates hyperplastic phenotypes through activation of epidermal growth factor receptor and hypoxia-inducible factor-2α.

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You Mie Lee

Full Text Available Reversion-inducing cysteine-rich protein with Kazal motifs (RECK, a tumor suppressor is down-regulated by the oncogenic signals and hypoxia, but the biological function of RECK in early tumorigenic hyperplastic phenotypes is largely unknown. Knockdown of RECK by small interfering RNA (siRECK or hypoxia significantly promoted cell proliferation in various normal epithelial cells. Hypoxia as well as knockdown of RECK by siRNA increased the cell cycle progression, the levels of cyclin D1 and c-Myc, and the phosphorylation of Rb protein (p-pRb, but decreased the expression of p21(cip1, p27(kip1, and p16(ink4A. HIF-2α was upregulated by knockdown of RECK, indicating HIF-2α is a downstream target of RECK. As knockdown of RECK induced the activation of epidermal growth factor receptor (EGFR and treatment of an EGFR kinase inhibitor, gefitinib, suppressed HIF-2α expression induced by the silencing of RECK, we can suggest that the RECK silenicng-EGFR-HIF-2α axis might be a key molecular mechanism to induce hyperplastic phenotype of epithelial cells. It was also found that shRNA of RECK induced larger and more numerous colonies than control cells in an anchorage-independent colony formation assay. Using a xenograft assay, epithelial cells with stably transfected with shRNA of RECK formed a solid mass earlier and larger than those with control cells in nude mice. In conclusion, the suppression of RECK may promote the development of early tumorigenic hyperplastic characteristics in hypoxic stress.

Obesity-related gene ADRB2, ADRB3 and GHRL polymorphisms and the response to a weight loss diet intervention in adult women

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Louise F. Saliba

2014-01-01

Full Text Available The individual response to diet may be influenced by gene polymorphisms. This study hypothesized that ADRB2 (Gln27Glu, rs1042714 and Arg16Gly, rs1042713, ADRB3 (Trp64Arg, rs4994 and GHRL (Leu72Met, rs696217 polymorphisms moderate weight loss. The study was a seven weeks dietary weight loss intervention with Brazilian adult obese women (n = 109. The body mass index (BMI was calculated and polymorphisms in these genes were assessed by real-time PCR assays. Two-way repeated-measures ANOVA (2 x 2 were used to analyze the intervention effect between polymorphisms and BMI over the period and after stratification for age and socioeconomic status (SES. The weight loss intervention resulted in decreased BMI over the seven-week period (p < 0.001, for high and low SES (p < 0.05 and mainly for participants with 30-49 y. The intervention did not result in a statistically significant difference in weight loss between polymorphism carriers and non-carriers, and although, the ADRB2, ADRB3 and GHRL polymorphisms did not moderate weight loss, the Gln27Glu polymorphism carriers showed a lower BMI compared to non-carriers in the low SES (p = 0.018 and the 30-39 y (p = 0.036 groups, suggesting a role for this polymorphism related to BMI control.

Fibromyalgia, mood disorders, and intense creative energy: A1AT polymorphisms are not always silent.

Science.gov (United States)

Schmechel, Donald E; Edwards, Christopher L

2012-12-01

Persons with single copies of common alpha-1-antitrypsin polymorphisms such as S and Z are often considered "silent carriers". Published evidence however supports a complex behavioral phenotype or trait - intense creative energy ("ICE")-associated with A1AT polymorphisms. We now confirm that phenotype and present an association of fibromyalgia syndrome (FMS) and A1AT in a consecutive series of neurological patients. This is a retrospective case control series of 3176 consecutive patients presenting to Duke University Memory Clinic (747 patients) and to regional community-based Caldwell Hospital Neurology and Memory center (2429 patients). Work-up included medical history and examination, psychological evaluation, and genetic analysis. Chronic widespread pain (CWP) or FMS were diagnosed according to clinical guidelines, mostly as secondary diagnoses. Neurological patients carrying A1AT polymorphisms were common (ca 16% prevalence) and carriers had significantly higher use of inhaler and anxiolytic medications. Patients with ICE phenotype had a significantly higher proportion of A1AT polymorphisms (42%) compared to non-ICE patients (13%). Presence of CWP or FMS was common (14-22%) with average age at presentation of 56 years old and mostly female gender (82%). Patients with CWP/FMS had again significantly higher proportion of A1AT polymorphisms (38%) compared to other neurological patients (13%). Patients with anxiety disorders, bipolar I or bipolar II disorders or PTSD also had increased proportion of A1AT polymorphisms and significant overlap with ICE and FMS phenotype. Significant reductions in CWP/FMS prevalence are seen in apolipoprotein E4 carriers and methylene tetrahydrofolate reductase (MTHFR) mutation homozygotes. Since ICE phenotype is reported as a lifelong behavioral attribute, the presumption is that A1AT carriers have fundamental differences in brain development and inflammatory response. In support of this concept is finding those persons reporting a

ACE Gene I/D Polymorphism and Obesity in 1,574 Patients with Type 2 Diabetes Mellitus.

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Pan, Yan-Hong; Wang, Min; Huang, Yan-Mei; Wang, Ying-Hui; Chen, Yin-Ling; Geng, Li-Jun; Zhang, Xiao-Xi; Zhao, Hai-Lu

2016-01-01

Association between ACE gene I/D polymorphism and the risk of overweight/obesity remains controversial. We investigated the possible relationship between ACE gene I/D polymorphism and obesity in Chinese type 2 diabetes mellitus (T2DM) patients. In this study, obesity was defined as a body mass index (BMI) value ≥ 25 kg/m 2 and subjects were classified into 4 groups (lean, normal, overweight, and obese). PCR (polymerase chain reaction) was used to detect the ACE gene I/D polymorphism in T2DM patients. Metabolic measurements including blood glucose, lipid profile, and blood pressure were obtained. Frequencies of the ACE genotypes (DD, ID, and II) were not significant among the 4 groups of BMI-defined patients ( P = 0.679) while ACE II carriers showed higher systolic blood pressure (SBP) and pulse pressure (PP) (all P ACE gene I/D polymorphism with obesity is insignificant in Chinese patients with T2DM. SBP and PP might be higher in the ACE II carriers than in the DD and ID carriers.

The impact of a TSH receptor gene polymorphism on thyroid-related phenotypes in a healthy Danish twin population

DEFF Research Database (Denmark)

Hansen, Pia Skov; van der Deure, Wendy M; Peeters, Robin P

2007-01-01

OBJECTIVES: The Asp727Glu polymorphism in the TSH receptor (TSHR) gene is associated with serum TSH levels. However, the proportion of genetic variation accounted for by this polymorphism is unknown. In this study, we (1) examined the association of the Asp727Glu polymorphism with thyroid size...... between the TSHR-Asp727Glu polymorphism and measures of thyroid homeostasis were assessed and the effect of the polymorphism on the trait's phenotypic variability was quantified by incorporating the genotype information in structural equation modelling. RESULTS: The genotype distribution was Asp/Asp 84.......9%; Asp/Glu 14.5% and Glu/Glu 0.6%. Carriers of the TSHR-Glu727 allele had lower TSH levels (noncarriers vs. carriers: 1.78 +/- 0.93 vs. 1.60 +/- 0.84 mU/l, P = 0.04). Regression analysis showed an association between the TSHR-Asp727Glu polymorphism and serum TSH (P = 0.007). The polymorphism accounted...

Assessment of the rs4340 ACE gene polymorphism in acute coronary syndrome in a Western Mexican population.

Science.gov (United States)

Valdez-Haro, A; Valle, Y; Valdes-Alvarado, E; Casillas-Muñoz, F; Muñoz-Valle, J F; Reynoso-Villalpando, G L; Flores-Salinas, H E; Padilla-Gutiérrez, J R

2017-09-27

Acute coronary syndrome (ACS) is considered one of the main causes of death worldwide. Contradictory findings concerning the impact of the angiotensin-converting enzyme (ACE) gene on cardiovascular diseases have been reported. Previous conclusions point out that the variability in results depends on ethnicity and genetic polymorphisms to determine the association of rs4340 polymorphisms of the ACE gene and ACE circulating levels in ACS. Genotyping of rs4340 polymorphisms was performed in a total of 600 individuals from Western Mexico divided into two groups: the ACS and the control group (CG). The polymorphisms were identified by polymerase chain reaction. Serum ACE concentration was determined by enzyme-linked immunosorbent assay. D/D carriers had higher ACE levels than I/I carriers (3.6 vs 2.8 ng/mL, P ACE concentration levels; however, the polymorphism was not associated with ACS.

Micro-Evolution in Grasshoppers Mediated by Polymorphic Robertsonian Translocations

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Colombo, Pablo C.

2013-01-01

This review focuses on grasshoppers that are polymorphic for Robertsonian translocations because in these organisms the clarity of meiotic figures allows the study of both chiasma distribution and the orientation of trivalents and multivalents in metaphase I. Only five species of such grasshoppers were found in the literature, and all of them were from the New World: Oedaleonotus enigma (Scudder) (Orthoptera: Acrididae), Leptysma argentina Bruner, Dichroplus pratensis Bruner, Sinipta dalmani Stål, and Cornops aquaticum Bruner. A general feature of these species (except O. enigma) is that fusion carriers suffer a marked reduction of proximal and interstitial (with respect to the centromere) chiasma frequency; this fact, along with the reduction in the number of linkage groups with the consequent loss of independent segregation, produces a marked decrease of recombination in fusion carriers. This reduction in recombination has led to the conclusion that Robertsonian polymorphic grasshopper species share some properties with inversion polymorphic species of Drosophila, such as the central-marginal pattern (marginal populations are monomorphic, central populations are highly polymorphic). This pattern might be present in D. pratensis, which is certainly the most complex Robertsonian polymorphism system in the present study. However, L. argentina and C. aquaticum do not display this pattern. This issue is open to further research. Since C. aquaticum is soon to be released in South Africa as a biological control, the latitudinal pattern found in South America may repeat there. This experiment's outcome is open and deserves to be followed. PMID:23909914

A NOS3 polymorphism determines endothelial response to folate in children with type 1 diabetes or obesity.

Science.gov (United States)

Wiltshire, Esko J; Peña, Alexia S; MacKenzie, Karen; Bose-Sundernathan, Tulika; Gent, Roger; Couper, Jennifer J

2015-02-01

To determine the effect of polymorphisms in NOS3 and folate pathway enzymes on vascular function and folate status and endothelial response to folate in children with diabetes or obesity. A total of 244 subjects (age 13.8 ± 2.8 years, 125 males) were studied for NOS3 and/or folate pathway polymorphisms using polymerase chain reaction/restriction fragment length polymorphism, including at baseline: 139 with type 1 diabetes; 58 with obesity; and 47 controls. The effect of NOS3 genotype on endothelial response to folate (5 mg) was assessed in 85 subjects with diabetes and 28 obese subjects who received active treatment during intervention trials. Vascular function (flow-mediated dilatation [FMD] and glyceryl trinitrate-mediated dilatation), clinical, and biochemical measurements were assessed at baseline and 8 weeks in folate intervention studies. Folate pathway enzyme and NOS3 polymorphisms did not significantly affect baseline vascular function. The polymorphism in intron 4 of endothelial nitric oxide synthase altered endothelial response to folate significantly: in subjects with diabetes FMD improved by 6.4 ± 5% (insertion carriers) vs 2.3 ± 6.6% (deletion carriers), P = .01; in obese subjects FMD improved by 1.8 ± 5.4% (insertion carriers) and deteriorated by -3.2 ± 7.2% (deletion carriers), P = .05. More subjects carrying the insertion normalized FMD after folate supplementation (insertion 64% vs deletion 28%, χ(2) = 10.14, P = .001). A NOS3 polymorphism predicts endothelial response to folate in children with diabetes or obesity, with implications for vascular risk and folate intervention studies. Copyright © 2015 Elsevier Inc. All rights reserved.

VKORC1 polymorphisms and warfarin maintenance dose in population of Sakha (Yakuts).

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Chertovskikh, Y V; Malova, E U; Maksimova, N R; Popova, N V; Sychev, D A

2015-01-01

Vitamin K antagonists are effective in the prevention and treatment of thromboembolic disorders. Warfarin is one of the most widely prescribed vitamin K antagonists in the world [1, 2]. It has a narrow therapeutic range and a given dose may result in a large inter-individual variation of response. Insufficient dose may fail to prevent thromboembolism, while an overdose increases the risk of bleeding. Patient-specific factors (e.g., age, body size, race, concurrent diseases, and medications) explain some of the variability in warfarin dosage, but genetic factors influencing warfarin response explain a significantly higher proportion of this variability [3]. Molecular analysis of the gene that encodes the target enzyme vitamin K epoxide reductase complex 1 (VKORC1) strongly suggests that its genetic variations greatly affect the individual response to oral anticoagulants [4-7]. To evaluate effects of VKORC1 polymorphisms on warfarin dose excess anticoagulation (INR >4.0) in the population of Sakha (S) patients. 53 patients (29-women, 24-men) with atrial fibrillation (68%), congestive heart failure (60%), hypertension (49%) and cardiac valve replacement (26%) were recruited. The age range was 26-80 years, with a mean age of 62.87 ± 12.57 years.International normalized ratio and plasma warfarin concentrations were determined. Genotyping was carried out by RT-PCR (real-time PCR). The three genetic polymorphisms of the gene VKORC1 G3673A (rs9923231) were studied: normal (GG), heterozygous (GA) and homozygous (AA). Fisher exact probability test and chi-square test (with Yates correction) were applied to compare data among the AA and GG + GA groups; also Mann-Whitney test was used. The median maintenance daily dose of warfarin among AA carriers was 3.0 mg/day [1.25-7.5 mg], while in GG and GA patients it was 3.13 mg/day [1.88-7.92 mg]. The mean daily warfarin dosage was higher in GG and GA genotype carriers 4.05 mg/day (SD ± 1.7) than in patients with AA genotype 3

Preproghrelin Leu72Met polymorphism is not associated with type 2 diabetes mellitus.

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Kim, Sun-Young; Jo, Dae-Sun; Hwang, Pyoung Han; Park, Ji Hyun; Park, Sung Kwang; Yi, Ho Keun; Lee, Dae-Yeol

2006-03-01

Ghrelin is a novel gut-brain peptide, which exerts somatotropic, orexigenic, and adipogenic effects. Genetic variants of ghrelin have been associated with both obesity and insulin metabolism. In this study, we determined a role of preproghrelin Leu72Met polymorphism on type 2 diabetes mellitus and its relationship to variables studied. Genotypes were assessed by polymerase chain reaction. Frequencies of the Leu72Met polymorphism were found to be 35.4% in the type 2 diabetic patients and 32.5% in the normal controls. The Leu72Met polymorphism was not associated with hypertension, macroangiopathy, retinopathy, serum cholesterol, triglyceride, blood urea nitrogen, HbA(1c), lipoprotein (a), fasting insulin, or 24-hour urinary protein levels in the type 2 diabetic group. However, the Leu72Met polymorphism was clearly associated with serum creatinine levels in the diabetic group, as the Met72 carriers exhibited lower serum creatinine levels than the Met72 noncarriers. Our data indicate that the preproghrelin Leu72Met polymorphism is not associated with type 2 diabetes mellitus. However, the Leu72Met polymorphism is associated with serum creatinine levels. These data suggest that Met72 carrier status may be a predictable marker for diabetic nephropathy or renal impairment in type 2 diabetes mellitus.

Linkage disequilibria among (CA){sub n} polymorphisms in the human dystrophin gene and their implications in carrier detection and prenatal diagnosis in Duchenne and Becker musclar dystrophies

Energy Technology Data Exchange (ETDEWEB)

Chakraborty, R.; Zhong, Y.; Andrade, M. de [Univ. of Texas Graduate School of Biomedical Sciences, Houston, TX (United States)] [and others

1994-06-01

Four short tandem repeat loci, characterized by length polymorphisms of (CA){sub n} repeats, have been detected within introns 44, 45, 49, and 50 of the human dystrophin gene. The predicted heterozygosites for these loci range from 72 to 93%, and observed allele numbers range from 6 to 19 in 57 normal chromosomes, revealing their high degree of polymorphism. Evidence for significant disequilibria between the loci within introns 49 and 50 is found. These data appear to be consistent with observations of recombination frequencies between these markers and the length of the intron 44 in relation to the entire region. In addition, these four loci are collectively found to be 100% informative in carrier detection/prenatal diagnosis of Becker and Duchenne muscular dystrophies (B/DMD), whereas scoring the (CA){sub n} markers within introns 45 and 49 alone gives a 99.6% success rate. 13 refs., 4 tabs.

APOA2 Polymorphism in Relation to Obesity and Lipid Metabolism

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Moushira Erfan Zaki

2013-01-01

Full Text Available Objectives. This study aims to analysis the relationship between c.-492T>C polymorphism in APOA2 gene and the risk for obesity in a sample of Egyptian adolescents and investigates its effect on body fat distribution and lipid metabolism. Material and Methods. A descriptive, cross-sectional study was conducted on 303 adolescents. They were 196 obese and 107 nonobese, aged 16–19 years old. Variables examined included body mass index (BMI, waist circumference (WC, waist to hip ratio (WHR, systolic and diastolic blood pressure (BP, body fat percentage (BF%, abdominal visceral fat layer, and dietary intake. Abdominal visceral fat thickness was determined by ultrasonography. The polymorphism in the APOA2 c.-492T>C was analyzed by PCR amplification. Results. Genotype frequencies were in Hardy-Weinberg equilibrium. The frequency of the mutant C allele was significantly higher in obese cases compared to nonobese. After multivariate adjustment, waist, BF% and visceral adipose layer, food consumption, and HDL-C were significantly higher in homozygous allele CC carriers than TT+TC carriers. Conclusions. Homozygous individuals for the C allele had higher obesity risk than carriers of the T allele and had elevated levels of visceral adipose tissue and serum HDL-C. Moreover, the study shows association between the APOA2 c.-492T>C polymorphism and food consumption.

AT1 Receptor Gene Polymorphisms in relation to Postprandial Lipemia

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B. Klop

2012-01-01

Full Text Available Background. Recent data suggest that the renin-angiotensin system may be involved in triglyceride (TG metabolism. We explored the effect of the common A1166C and C573T polymorphisms of the angiotensin II type 1 receptor (AT1R gene on postprandial lipemia. Methods. Eighty-two subjects measured daytime capillary TG, and postprandial lipemia was estimated as incremental area under the TG curve. The C573T and A1166C polymorphisms of the AT1R gene were determined. Results. Postprandial lipemia was significantly higher in homozygous carriers of the 1166-C allele (9.39±8.36 mM*h/L compared to homozygous carriers of the 1166-A allele (2.02±6.20 mM*h/L (P<0.05. Postprandial lipemia was similar for the different C573T polymorphisms. Conclusion. The 1166-C allele of the AT1R gene seems to be associated with increased postprandial lipemia. These data confirm the earlier described relationships between the renin-angiotensin axis and triglyceride metabolism.

Polymorphisms in NFkB, PXR, LXR and risk of colorectal cancer in a prospective study of Danes

DEFF Research Database (Denmark)

Andersen, Vibeke; Christensen, Jane; Overvad, Kim

2010-01-01

. There was no interaction between use of nonsteroid antiinflammatory drugs (NSAID) or smoking status and NFkB, PXR or LXR polymorphisms. Conclusions A polymorphism in NFkB was associated with CRC risk and there was interaction between this polymorphism and meat intake in relation to CRC risk. This study suggests a role......-B, pregnane X receptor, and liver X receptor were associated with risk of CRC, and to investigate possible interactions with lifestyle factors such as smoking, meat consumption, and NSAID use. Methods The polymorphisms nuclear factor kappa-B (NFkB, NFKB1) -94 insertion/deletion ATTG (rs28362491), pregnane X...... and Health study of 57,053 persons. Results Carriers of NFkB -94deletion were at 1.45-fold higher risk of CRC than homozygous carriers of the insertion allele (incidence rate ratio (IRR) = 1.45, 95% confidence interval (95% CI): 1.10-1.92). There was interaction between this polymorphism and intake of red...

The common polymorphism of apolipoprotein E

DEFF Research Database (Denmark)

Gerdes, Ulrik

2003-01-01

from only 10-15% in southern Europe to 40-50% in the north. The gradient may be a trace of the demic expansion of agriculture that began about 10,000 years ago, but it may also reflect the possibility that APOE*4 carriers are less likely to develop vitamin D deficiency. The common APOE polymorphism......Apolipoprotein E (apoE) has important functions in systemic and local lipid transport, but also has other functions. The gene (APOE) shows a common polymorphism with three alleles--APOE*2, APOE*3, and APOE*4. Their frequencies vary substantially around the world, but APOE*3 is the most common...

Polymorphisms in folate pathway and pemetrexed treatment outcome in patients with malignant pleural mesothelioma

International Nuclear Information System (INIS)

Goricar, Katja; Kovac, Viljem; Dolzan, Vita

2014-01-01

A combination of pemetrexed and cisplatin has been shown to improve the outcome in patients with malignant pleural mesothelioma (MPM), however, there is a great heterogeneity in treatment response among patients. The aim of our study was to evaluate the influence of polymorphisms in folate pathway and transporter genes on pemetrexed treatment outcome in Slovenian patients with MPM. MPM patients treated with pemetrexed in the course of a prospective randomized clinical trial were genotyped for nineteen polymorphisms in five genes of folate pathway and six transporter genes. Logistic regression was used to assess the influence of polymorphisms on treatment efficacy and toxicity, while Cox regression was used to determine their influence on progression-free and overall survival. Patients with at least one polymorphic MTHFD1 rs2236225 allele had a significantly lower response rate (p = 0.005; odds ratio [OR] = 0.12; 95% confidence interval [CI] = 0.03−0.54) and shorter progression-free survival (p = 0.032; hazard ratio [HR] = 3.10; 95% CI = 1.10−8.74) than non-carriers. Polymorphisms in transporter genes did not influence survival; however, several were associated with toxicity. Liver toxicity was significantly lower in carriers of polymorphic ABCC2 rs2273697 (p = 0.028; OR = 0.23; 95% CI = 0.06−0.85), SLCO1B1 rs4149056 (p = 0.028; OR = 0.23; 95% CI = 0.06−0.85) and rs11045879 (p = 0.014; OR = 0.18; 95% CI = 0.05−0.71) alleles compared to non-carriers, as well as in patients with SLCO1B1 GCAC haplotype (p = 0.048; OR = 0.17; 95% CI = 0.03−0.98). Gastrointestinal toxicity was much more common in patients with polymorphic ABCC2 rs717620 allele (p = 0.004; OR = 10.67; 95% CI = 2.15−52.85) and ABCC2 CAG haplotype (p = 0.006; OR = 5.67; 95% CI = 1.64−19.66). MTHFD1 polymorphism affected treatment response and survival, while polymorphisms in ABCC2 and SLCO1B1 transporter genes influenced the risk for toxicity. These polymorphisms could serve as potential

MODULATING EFFECT OF THE −158 GΓ (C→T XMN-1 POLYMORPHISM IN INDIAN SICKLE CELL PATIENTS

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Sanjay Pandey

2012-01-01

Full Text Available Xmn-1 polymorphism is a known factor, which increases fetal haemoglobin production. Among the inherited disorders of blood, thalassaemia and SCD constitutes a major bulk of genetic diseases in India.  Our aim was to verify the role of the Xmn I polymorphism as a modulating factor in sickle cell patients and frequency of the polymorphism in Indian sickle cell patients. Subjects were 60 sickles homozygous and 75 sickle beta thalassemia patients. 5 ml blood   samples collected from patients. Screening of sickle patients done by HPLC. An automated cell analyzer SYSMEX (K-4500 Model used to analyze the CBC of patients.Xmn1 polymorphism analysis done by PCR-RFLP and Statistical analysis was performed on GraphPad static’s software. t test applied to compare the means amongst group. Among the sickle homozygous 27 were   heterozygous (+/- and 19 were   homozygous (+/+ while 30 were heterozygous and 24 were homozygous in sickle β-thalassemia patients. Extremely significant differences (p-value <0.001 of hematological parameters seen among patient with xmn-1 carrier and without the xmn-1 carrier. In our cases the clinical symptom less frequent and higher HbF level with Xmn-1 carriers. Presence of Xmn-1 polymorphism in sickle patients with higher HbF that improve phenotypic presentation in the sickle cell patients. We conclude that the phenotype of Indian sickle cell patients influenced by Xmn-1 polymorphism.

An APOA1 promoter polymorphism is associated with cognitive performance in patients with multiple sclerosis.

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Koutsis, G; Panas, M; Giogkaraki, E; Karadima, G; Sfagos, C; Vassilopoulos, D

2009-02-01

Elevated ApoA1 levels have been associated with decreased dementia risk. The A-allele of the APOA1 -75G/A promoter polymorphism has been associated with elevated ApoA1 levels. We sought to investigate the effect of the APOA1 -75G/A promoter polymorphism on cognitive performance in patients with multiple sclerosis (MS). A total of 138 patients with MS and 43 controls were studied and underwent neuropsychological assessment with Rao's Brief Repeatable Battery and the Stroop test. All patients were genotyped for APOA1. APOA1 A-allele carriers displayed superior overall cognitive performance compared with non-carriers (P 0.008) and had a three-fold decrease in the relative risk of overall cognitive impairment (OR 0.29, 95% CI 0.11-0.74). Regarding performance on individual cognitive domains, although APOA1 A-allele carriers performed better than non-carriers on all tests, this was significant only for semantic verbal fluency and the Stroop interference task (P 0.036 and 0.018, respectively). We found an association of the APOA1 -75G/A promoter polymorphism with cognitive performance in MS. This effect was most prominent on semantic verbal fluency and the Stroop interference task.

Polymorphisms in NFkB, PXR, LXR and risk of colorectal cancer in a prospective study of Danes

International Nuclear Information System (INIS)

Andersen, Vibeke; Christensen, Jane; Overvad, Kim; Tjønneland, Anne; Vogel, Ulla

2010-01-01

Transcription factors and nuclear receptors constitute a link between exposure to heterocyclic amines and polycyclic aromatic hydrocarbons from meat and tobacco smoke and colorectal cancer (CRC) risk. The aim of this study was to investigate if polymorphisms in nuclear factor kappa-B, pregnane X receptor, and liver X receptor were associated with risk of CRC, and to investigate possible interactions with lifestyle factors such as smoking, meat consumption, and NSAID use. The polymorphisms nuclear factor kappa-B (NFkB, NFKB1) -94 insertion/deletion ATTG (rs28362491), pregnane X receptor (PXR, NR1I2) A-24381C (rs1523127), C8055T (rs2276707), A7635G (rs6785049), liver X receptor (LXR-β, NR1H3) C-rs1405655T, T-rs2695121C were assessed together with lifestyle factors in a nested case-cohort study of 378 CRC cases and 756 random participants from the Danish prospective Diet, Cancer and Health study of 57,053 persons. Carriers of NFkB -94deletion were at 1.45-fold higher risk of CRC than homozygous carriers of the insertion allele (incidence rate ratio (IRR) = 1.45, 95% confidence interval (95% CI): 1.10-1.92). There was interaction between this polymorphism and intake of red and processed meat in relation to CRC risk. Carriers of NFkB -94deletion were at 3% increased risk pr 25 gram meat per day (95% CI: 0.98-1.09) whereas homozygous carriers of the insertion were not at increased risk (p for interaction = 0.03). PXR and LXR polymorphisms were not associated with CRC risk. There was no interaction between use of nonsteroid antiinflammatory drugs (NSAID) or smoking status and NFkB, PXR or LXR polymorphisms. A polymorphism in NFkB was associated with CRC risk and there was interaction between this polymorphism and meat intake in relation to CRC risk. This study suggests a role for NFkB in CRC aetiology

Polymorphisms in NFkB, PXR, LXR and risk of colorectal cancer in a prospective study of Danes

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Andersen Vibeke

2010-09-01

Full Text Available Abstract Background Transcription factors and nuclear receptors constitute a link between exposure to heterocyclic amines and polycyclic aromatic hydrocarbons from meat and tobacco smoke and colorectal cancer (CRC risk. The aim of this study was to investigate if polymorphisms in nuclear factor kappa-B, pregnane X receptor, and liver X receptor were associated with risk of CRC, and to investigate possible interactions with lifestyle factors such as smoking, meat consumption, and NSAID use. Methods The polymorphisms nuclear factor kappa-B (NFkB, NFKB1 -94 insertion/deletion ATTG (rs28362491, pregnane X receptor (PXR, NR1I2 A-24381C (rs1523127, C8055T (rs2276707, A7635G (rs6785049, liver X receptor (LXR-β, NR1H3 C-rs1405655T, T-rs2695121C were assessed together with lifestyle factors in a nested case-cohort study of 378 CRC cases and 756 random participants from the Danish prospective Diet, Cancer and Health study of 57,053 persons. Results Carriers of NFkB -94deletion were at 1.45-fold higher risk of CRC than homozygous carriers of the insertion allele (incidence rate ratio (IRR = 1.45, 95% confidence interval (95% CI: 1.10-1.92. There was interaction between this polymorphism and intake of red and processed meat in relation to CRC risk. Carriers of NFkB -94deletion were at 3% increased risk pr 25 gram meat per day (95% CI: 0.98-1.09 whereas homozygous carriers of the insertion were not at increased risk (p for interaction = 0.03. PXR and LXR polymorphisms were not associated with CRC risk. There was no interaction between use of nonsteroid antiinflammatory drugs (NSAID or smoking status and NFkB, PXR or LXR polymorphisms. Conclusions A polymorphism in NFkB was associated with CRC risk and there was interaction between this polymorphism and meat intake in relation to CRC risk. This study suggests a role for NFkB in CRC aetiology.

The BDNF Val66Met Polymorphism Affects the Vulnerability of the Brain Structural Network

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Chang-hyun Park

2017-08-01

Full Text Available Val66Met, a naturally occurring polymorphism in the human brain-derived neurotrophic factor (BDNF gene resulting in a valine (Val to methionine (Met substitution at codon 66, plays an important role in neuroplasticity. While the effect of the BDNF Val66Met polymorphism on local brain structures has previously been examined, its impact on the configuration of the graph-based white matter structural networks is yet to be investigated. In the current study, we assessed the effect of the BDNF polymorphism on the network properties and robustness of the graph-based white matter structural networks. Graph theory was employed to investigate the structural connectivity derived from white matter tractography in two groups, Val homozygotes (n = 18 and Met-allele carriers (n = 55. Although there were no differences in the global network measures including global efficiency, local efficiency, and modularity between the two genotype groups, we found the effect of the BDNF Val66Met polymorphism on the robustness properties of the white matter structural networks. Specifically, the white matter structural networks of the Met-allele carrier group showed higher vulnerability to targeted removal of central nodes as compared with those of the Val homozygote group. These findings suggest that the central role of the BDNF Val66Met polymorphism in regards to neuroplasticity may be associated with inherent differences in the robustness of the white matter structural network according to the genetic variants. Furthermore, greater susceptibility to brain disorders in Met-allele carriers may be understood as being due to their limited stability in white matter structural connectivity.

A functional polymorphism in the reduced folate carrier gene and DNA hypomethylation in mothers of children with autism.

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James, S Jill; Melnyk, Stepan; Jernigan, Stefanie; Pavliv, Oleksandra; Trusty, Timothy; Lehman, Sara; Seidel, Lisa; Gaylor, David W; Cleves, Mario A

2010-09-01

The biologic basis of autism is complex and is thought to involve multiple and variable gene-environment interactions. While the logical focus has been on the affected child, the impact of maternal genetics on intrauterine microenvironment during pivotal developmental windows could be substantial. Folate-dependent one carbon metabolism is a highly polymorphic pathway that regulates the distribution of one-carbon derivatives between DNA synthesis (proliferation) and DNA methylation (cell-specific gene expression and differentiation). These pathways are essential to support the programmed shifts between proliferation and differentiation during embryogenesis and organogenesis. Maternal genetic variants that compromise intrauterine availability of folate derivatives could alter fetal cell trajectories and disrupt normal neurodevelopment. In this investigation, the frequency of common functional polymorphisms in the folate pathway was investigated in a large population-based sample of autism case-parent triads. In case-control analysis, a significant increase in the reduced folate carrier (RFC1) G allele frequency was found among case mothers, but not among fathers or affected children. Subsequent log linear analysis of the RFC1 A80G genotype within family trios revealed that the maternal G allele was associated with a significant increase in risk of autism whereas the inherited genotype of the child was not. Further, maternal DNA from the autism mothers was found to be significantly hypomethylated relative to reference control DNA. Metabolic profiling indicated that plasma homocysteine, adenosine, and S-adenosylhomocyteine were significantly elevated among autism mothers consistent with reduced methylation capacity and DNA hypomethylation. Together, these results suggest that the maternal genetics/epigenetics may influence fetal predisposition to autism. (c) 2010 Wiley-Liss, Inc.

Rapid DNA haplotyping using a multiplex heteroduplex approach: Application to Duchenne muscula dystrophy carrier detection

Energy Technology Data Exchange (ETDEWEB)

Prior, T.W.; Wenger, G.D.; Moore, J. [Ohio State Univ., Columbus, OH (United States)] [and others

1994-09-01

A new strategy has been developed for rapid haplotype analysis. It is based on an initial multiplex amplification of several polymorphic sites, followed by heteroduplex detection. Heteroduplexes formed between two different alleles are detected because they migrate differently than the corresponding homoduplexes in Hydrolink-MDE gel. The method is simple, rapid, does not depend on specific sequences such as restriction enzyme sites or CA boxes and does not require the use of isotope. This approach has been tested using 12 commonly occurring polymorphisms spanning the dystrophin gene as a model. We describe the use of the method to assign the carrier status of females in Duchenne muscular dystrophy (DMD) pedigrees. As a result of expanding the number of detectable polymorphisms throughout the dystrophin gene, we show how the method can easily be combined with dinucleotide analysis to improve the accuracy of carrier detection in the nondeletion cases. The technique is also shown to be used as an effective screen for improving carrier detection in several families with deletions. The finding of heterozygosity within the deletion identifies the at-risk female as a noncarrier. Using this method, we have identified and incorporated 3 new dystrophin polymorphisms (one of which in exon 16 is unique to African Americans). The method may be used other genetic diseases when mutations are unknown, or there are few dinucleotide markers in the gene proximity, or for the identification of haplotype backgrounds of mutant alleles.

5-HTTLPR polymorphism modulates neural mechanisms of negative self-reflection.

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Ma, Yina; Li, Bingfeng; Wang, Chenbo; Shi, Zhenhao; Sun, Yun; Sheng, Feng; Zhang, Yifan; Zhang, Wenxia; Rao, Yi; Han, Shihui

2014-09-01

Cognitive distortion in depression is characterized by enhanced negative thoughts about both environment and oneself. Carriers of a risk allele for depression, that is, the short (s) allele of the serotonin transporter promoter polymorphism (5-HTTLPR), exhibit amygdala hyperresponsiveness to negative environmental stimuli relative to homozygous long variant (l/l). However, the neural correlates of negative self-schema in s allele carriers remain unknown. Using functional MRI, we scanned individuals with s/s or l/l genotype of the 5-HTTLPR during reflection on their own personality traits or a friend's personality traits. We found that relative to l/l carriers, s/s carriers showed stronger distressed feelings and greater activity in the dorsal anterior cingulate (dACC)/dorsal medial prefrontal cortex (dmPFC) and the right anterior insula (AI) during negative self-reflection. The 5-HTTLPR effect on the distressed feelings was mediated by the AI/inferior frontal (IF) activity during negative self-reflection. The dACC/dmPFC activity explained 20% of the variation in harm-avoidance tendency in s/s but not l/l carriers. The genotype effects on distress and brain activity were not observed during reflection on a friend's negative traits. Our findings reveal that 5-HTTLPR polymorphism modulates distressed feelings and brain activities associated with negative self-schema and suggest a potential neurogenetic susceptibility mechanism for depression. © The Author 2013. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Association between polymorphism at 3 ׳UTR of urokinase gene and risk of calcium

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S. Morovvati

2016-06-01

Full Text Available Background: Kidney stone is a common multifactorial disease in Iran. Environmental and genetic factors including single nucleotide polymorphism (SNP affect the incidence of kidney stones. Objective: The aim of this study was to determine the association of +4065 T/C polymorphism at 3′untranslated region (3'UTR of urokinase gene and calcium kidney stones. Methods: This case-control study was conducted on 70 patients with history of calcium kidney stones as case group and 70 healthy subjects as control group in the Baqiyatallah hospital in 2013. The polymorphism was assessed using the Allele Specific PCR (AS-PCR method. Allele and genotype frequencies of the two groups were compared using 2x2 contingency tables. Hardy-Weinberg equilibrium was compared between the two groups using Chi-square test. Findings: Of 70 cases, 10 (15% were heterozygous and 24 (34% were homozygous for the polymorphism. Of 70 controls, 25 (35% were heterozygous for the polymorphism. The frequency of mutant T allele was 41% in the case group and 18% in the control group. The frequency of mutant C allele was 59% in the case group and 82% in the control group. The risk of calcium kidney stones in carriers of the mutant allele was 1.7 times higher than non-carriers (OR: 1.7. Conclusion: With regards to the results, it seems that there is a significant association between the polymorphism at 3 ׳UTR of urokinase gene and formation of calcium kidney stones. Urokinase gene polymorphism may be introduced as a candidate gene involved in calcium stone formation.

High-Pressure Polymorphism in Orthoamphiboles

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Finkelstein, G. J.; Zhang, D.; Shelton, H.; Dera, P.

2017-12-01

Amphiboles are double-chain silicate minerals that are the structurally hydrated counterpart to single-chain, anhydrous pyroxenes. They may play an important role in the earth as a carrier for volatiles in subduction zones, as well as a generator for seismic anisotropy in the upper mantle. Recent work has described previously unrecognized high-pressure polymorphism at low temperatures in a variety of pyroxene minerals, which may be relevant for the structure and dynamics of thick, cold, subducted slabs. However, high-pressure polymorphism in amphiboles above a few GPa in pressure has not been well explored, and if similar polymorphism to pyroxenes exists in this mineral family, it may affect the extent and depth of volatile transport in amphiboles, as well as their rheological properties. At low temperatures and high pressures, orthopyroxenes undergo crystal structure transitions at lower pressures than clinopyroxenes (10-30 GPa vs. > 50 GPa), so for this study we have investigated polymorphism in the anthophyllite-gedrite (Al-free and Al rich) orthoamphibole solid solution series. Using neon gas-loaded diamond anvil cells, we compressed both phases to a maximum pressure of 31 GPa, and observed transitions to new monoclinic structures in both endmembers. In this presentation, we will discuss the details of these transitions and implications for the earth's interior.

Gender differences in association between serotonin transporter gene polymorphism and resting-state EEG activity.

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Volf, N V; Belousova, L V; Knyazev, G G; Kulikov, A V

2015-01-22

Human brain oscillations represent important features of information processing and are highly heritable. Gender has been observed to affect association between the 5-HTTLPR (serotonin-transporter-linked polymorphic region) polymorphism and various endophenotypes. This study aimed to investigate the effects of 5-HTTLPR on the spontaneous electroencephalography (EEG) activity in healthy male and female subjects. DNA samples extracted from buccal swabs and resting EEG recorded at 60 standard leads were collected from 210 (101 men and 109 women) volunteers. Spectral EEG power estimates and cortical sources of EEG activity were investigated. It was shown that effects of 5-HTTLPR polymorphism on electrical activity of the brain vary as a function of gender. Women with the S/L genotype had greater global EEG power compared to men with the same genotype. In men, current source density was markedly different among genotype groups in only alpha 2 and alpha 3 frequency ranges: S/S allele carriers had higher current source density estimates in the left inferior parietal lobule in comparison with the L/L group. In women, genotype difference in global power asymmetry was found in the central-temporal region. Contrasting L/L and S/L genotype carriers also yielded significant effects in the right hemisphere inferior parietal lobule and the right postcentral gyrus with L/L genotype carriers showing lower current source density estimates than S/L genotype carriers in all but gamma bands. So, in women, the effects of 5-HTTLPR polymorphism were associated with modulation of the EEG activity in a wide range of EEG frequencies. The significance of the results lies in the demonstration of gene by sex interaction with resting EEG that has implications for understanding sex-related differences in affective states, emotion and cognition. Copyright © 2014 IBRO. Published by Elsevier Ltd. All rights reserved.

Aminoacid polymorphisms of insulin receptor substrate-1 in non-insulin-dependent diabetes mellitus

DEFF Research Database (Denmark)

Almind, K; Bjørbaek, C; Vestergaard, H

1993-01-01

Since relative or absolute insulin deficiency and insulin insensitivity are involved in the aetiology of non-insulin-dependent diabetes mellitus (NIDDM), we examined whether patients with NIDDM exhibit genetic variability in the coding region of insulin receptor substrate-1 (IRS-1), a candidate...... with NIDDM and 3 of the controls were heterozygous at codon 972 for a polymorphism in which glycine was substituted with arginine. Moreover, at codon 513, 6 patients with NIDDM and 2 controls had a heterozygous polymorphism with a transition from alanine to proline. None of the polymorphism carriers had both...

Influence of the IL-1Ra gene polymorphism on in vivo synthesis of IL-1Ra and IL-1beta after live yellow fever vaccination.

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Hacker, U T; Erhardt, S; Tschöp, K; Jelinek, T; Endres, S

2001-09-01

The inflammatory response in infectious and autoimmune diseases is regulated by the balance between pro- and anti-inflammatory cytokines. The IL-1 complex contains polymorphic genes coding for IL-1alpha, IL-1beta and IL-1Ra. The IL-1Ra (variable number of tanden repeat) VNTR polymorphism has been shown to influence the capacity to produce IL-1beta and IL-1Ra after in vitro stimulation. Allele 2 of this polymorphism is associated with a number of inflammatory diseases. To determine the impact of the IL-1Ra polymorphism on in vivo human cytokine synthesis, we used a yellow fever vaccination model for the induction of cytokine synthesis in healthy volunteers. Two different yellow fever vaccines were used. After administration of the RKI vaccine (34 volunteers), plasma TNF-alpha concentration increased from 13.4 +/- 0.9 pg/ml to 23.3 +/- 1.1 pg/ml (P < 0.001), and plasma IL-1Ra concentration increased from 308 +/- 25 pg/ml to 1019 +/- 111 pg/ml (P < 0.001), on day 2. Using Stamaril vaccine, no increase in the plasma concentrations of either TNF-alpha or IL-1Ra could be detected (n = 17). Only the RKI vaccine induced TNF-alpha synthesis after in vitro stimulation of MNC. Carriers of allele 2 of the IL-1Ra polymorphism had increased baseline concentrations of IL-1Ra (350 +/- 32 pg/ml) compared with non-carriers (222 +/- 18 pg/ml, P < 0.001), and decreased concentrations of IL-1beta (0.9 +/- 0.2 pg/ml for carriers versus 2.8 +/- 0.7 pg/ml for non-carriers, P = 0.017). After yellow fever vaccination (RKI vaccine), no significant differences in the increase of IL-1Ra plasma levels were detected between carriers and non-carriers of allele 2 of the IL-1Ra gene polymorphism. This is the first study to examine the influence of this genetic polymorphism on in vivo-induced human IL-1beta and IL-1Ra synthesis. Baseline concentrations of IL-1Ra and IL-1beta were significantly influenced by the IL-1Ra polymorphism. No influence of the IL-1Ra polymorphism on the in vivo

Distress of ostracism: oxytocin receptor gene polymorphism confers sensitivity to social exclusion.

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McQuaid, Robyn J; McInnis, Opal A; Matheson, Kimberly; Anisman, Hymie

2015-08-01

A single-nucleotide polymorphism on the oxytocin receptor gene (OXTR), rs53576, involving a guanine (G) to adenine (A) substitution has been associated with altered prosocial features. Specifically, individuals with the GG genotype (i.e. the absence of the polymorphism) display beneficial traits including enhanced trust, empathy and self-esteem. However, because G carriers might also be more socially sensitive, this may render them more vulnerable to the adverse effects of a negative social stressor. The current investigation, conducted among 128 white female undergraduate students, demonstrated that relative to individuals with AA genotype, G carriers were more emotionally sensitive (lower self-esteem) in response to social ostracism promoted through an on-line ball tossing game (Cyberball). Furthermore, GG individuals also exhibited altered blood pressure and cortisol levels following rejection, effects not apparent among A carriers. The data support the view that the presence of the G allele not only promotes prosocial behaviors but also favors sensitivity to a negative social stressor. © The Author (2015). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

Association of ghrelin polymorphisms with metabolic syndrome in Han Nationality Chinese.

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Xu, Ling-Ling; Xiang, Hong-Ding; Qiu, Chang-Chun; Xu, Qun

2008-06-01

To investigate the association of ghrelin gene polymorphisms with metabolic syndrome in Han Nationality Chinese. A total of 240 patients with metabolic syndrome and 427 adults aged above forty years were recruited. Genotypes were determined by polymerase chain reaction and restriction fragment length polymorphism analysis. The allelic frequency of the Leu72Met polymorphism was 17.3% in the patient group and 11.9% in the control group (chi2 = 7.36, P = 0.007). Metabolic syndrome was more prevalent among carriers of the Met72 variant (43.8 vs 33.1%, age- and sex-adjusted odds ratio = 1.57, P = 0.01). No Arg51Gln variants were found in our study subjects. Rather than being associated with its individual components, Leu72Met polymorphism is associated with metabolic syndrome in the Han Nationality Chinese. Arg51Gln polymorphism is rare in the Han Nationality Chinese.

DRD4 polymorphism moderates the effect of alcohol consumption on social bonding.

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Kasey G Creswell

Full Text Available Development of interpersonal relationships is a fundamental human motivation, and behaviors facilitating social bonding are prized. Some individuals experience enhanced reward from alcohol in social contexts and may be at heightened risk for developing and maintaining problematic drinking. We employed a 3 (group beverage condition ×2 (genotype design (N = 422 to test the moderating influence of the dopamine D4 receptor gene (DRD4 VNTR polymorphism on the effects of alcohol on social bonding. A significant gene x environment interaction showed that carriers of at least one copy of the 7-repeat allele reported higher social bonding in the alcohol, relative to placebo or control conditions, whereas alcohol did not affect ratings of 7-absent allele carriers. Carriers of the 7-repeat allele were especially sensitive to alcohol's effects on social bonding. These data converge with other recent gene-environment interaction findings implicating the DRD4 polymorphism in the development of alcohol use disorders, and results suggest a specific pathway by which social factors may increase risk for problematic drinking among 7-repeat carriers. More generally, our findings highlight the potential utility of employing transdisciplinary methods that integrate genetic methodologies, social psychology, and addiction theory to improve theories of alcohol use and abuse.

DRD4 polymorphism moderates the effect of alcohol consumption on social bonding.

Science.gov (United States)

Creswell, Kasey G; Sayette, Michael A; Manuck, Stephen B; Ferrell, Robert E; Hill, Shirley Y; Dimoff, John D

2012-01-01

Development of interpersonal relationships is a fundamental human motivation, and behaviors facilitating social bonding are prized. Some individuals experience enhanced reward from alcohol in social contexts and may be at heightened risk for developing and maintaining problematic drinking. We employed a 3 (group beverage condition) ×2 (genotype) design (N = 422) to test the moderating influence of the dopamine D4 receptor gene (DRD4 VNTR) polymorphism on the effects of alcohol on social bonding. A significant gene x environment interaction showed that carriers of at least one copy of the 7-repeat allele reported higher social bonding in the alcohol, relative to placebo or control conditions, whereas alcohol did not affect ratings of 7-absent allele carriers. Carriers of the 7-repeat allele were especially sensitive to alcohol's effects on social bonding. These data converge with other recent gene-environment interaction findings implicating the DRD4 polymorphism in the development of alcohol use disorders, and results suggest a specific pathway by which social factors may increase risk for problematic drinking among 7-repeat carriers. More generally, our findings highlight the potential utility of employing transdisciplinary methods that integrate genetic methodologies, social psychology, and addiction theory to improve theories of alcohol use and abuse.

Plasma metabolomics reveal alterations of sphingo- and glycerophospholipid levels in non-diabetic carriers of the transcription factor 7-like 2 polymorphism rs7903146.

Science.gov (United States)

Then, Cornelia; Wahl, Simone; Kirchhofer, Anna; Grallert, Harald; Krug, Susanne; Kastenmüller, Gabi; Römisch-Margl, Werner; Claussnitzer, Melina; Illig, Thomas; Heier, Margit; Meisinger, Christa; Adamski, Jerzy; Thorand, Barbara; Huth, Cornelia; Peters, Annette; Prehn, Cornelia; Heukamp, Ina; Laumen, Helmut; Lechner, Andreas; Hauner, Hans; Seissler, Jochen

2013-01-01

Polymorphisms in the transcription factor 7-like 2 (TCF7L2) gene have been shown to display a powerful association with type 2 diabetes. The aim of the present study was to evaluate metabolic alterations in carriers of a common TCF7L2 risk variant. Seventeen non-diabetic subjects carrying the T risk allele at the rs7903146 TCF7L2 locus and 24 subjects carrying no risk allele were submitted to intravenous glucose tolerance test and euglycemic-hyperinsulinemic clamp. Plasma samples were analysed for concentrations of 163 metabolites through targeted mass spectrometry. TCF7L2 risk allele carriers had a reduced first-phase insulin response and normal insulin sensitivity. Under fasting conditions, carriers of TCF7L2 rs7903146 exhibited a non-significant increase of plasma sphingomyelins (SMs), phosphatidylcholines (PCs) and lysophosphatidylcholines (lysoPCs) species. A significant genotype effect was detected in response to challenge tests in 6 SMs (C16:0, C16:1, C18:0, C18:1, C24:0, C24:1), 5 hydroxy-SMs (C14:1, C16:1, C22:1, C22:2, C24:1), 4 lysoPCs (C14:0, C16:0, C16:1, C17:0), 3 diacyl-PCs (C28:1, C36:6, C40:4) and 4 long-chain acyl-alkyl-PCs (C40:2, C40:5, C44:5, C44:6). Plasma metabolomic profiling identified alterations of phospholipid metabolism in response to challenge tests in subjects with TCF7L2 rs7903146 genotype. This may reflect a genotype-mediated link to early metabolic abnormalities prior to the development of disturbed glucose tolerance.

ACE insertion/deletion (I/D) polymorphism and diabetic nephropathy.

Science.gov (United States)

Rahimi, Zohreh

2012-10-01

Angiotensin converting enzyme (ACE) gene encodes ACE, a key component of renin angiotensin system (RAS), plays an important role in blood pressure homeostasis by generating the vasoconstrictor peptide angiotensin II. Directory of Open Access Journals (DOAJ), Google Scholar, Pubmed (NLM), LISTA (EBSCO) and Web of Science have been searched. The presence of ACE insertion/deletion (I/D) polymorphism affects the plasma level of ACE. ACE DD genotype is associated with the highest systemic and renal ACE levels compared with the lowest ACE activity in carriers of II genotype. In this review focus has been performed on the study of ACE I/D polymorphism in various populations and its influence on the risk of onset and progression of diabetic nephropathy. Also, association between ACE I/D polymorphism and response to ACE inhibitor and angiotensin II receptor antagonists will be reviewed. Further, synergistic effect of this polymorphism and variants of some genes on the risk of development of diabetic nephropathy will be discussed.

Reduced folate carrier polymorphism determines methotrexate uptake by B cells and CD4+ T cellsTumor necrosis factor-alpha binding capacity and anti-infliximab antibodies measured by fluid-phase radioimmunoassays as predictors of clinical efficacy of infliximab in Crohn's disease

DEFF Research Database (Denmark)

Baslund, B.; Gregers, J.; Nielsen, Claus Henrik

2008-01-01

OBJECTIVE: To examine if polymorphism 80G --> A in the Reduced Folate Carrier (RFC) affects uptake of MTX in B- and CD4+ T-cells. METHODS: Mononuclear cells were isolated from peripheral blood of healthy persons. Real-time PCR was used to detect the RFC80 variants. FITC-labelled MTX was added to ...

Polymorphisms in the xenobiotic transporter Multidrug Resistance 1 (MDR1 and interaction with meat intake in relation to risk of colorectal cancer in a Danish prospective case-cohort study

Directory of Open Access Journals (Sweden)

Overvad Kim

2009-11-01

Full Text Available Abstract Background The xenobiotic transporters, Multidrug Resistance 1 (MDR1/ABCB1 and Breast Cancer Resistance Protein (BCRP/ABCG2 may restrict intestinal absorption of various carcinogens, including heterocyclic amines (HCA and polycyclic aromatic hydrocarbons (PAH. Cyclooxygenase-2 (COX-2 derived prostaglandins promote gastrointestinal carcinogenesis, affecting angiogenesis, apoptosis, and invasiveness. The aim of this study was to investigate if polymorphisms in these genes were associated with risk of colorectal cancer (CRC, and to investigate possible interactions with lifestyle factors such as smoking, meat consumption, and NSAID use. Methods The following polymorphisms were analyzed; a synonymous MDR1 C3435T (rs1045642 in exon26, G-rs3789243-A in intron3, the functional BCRP C421A (rs2231142, the two COX-2 A-1195G (rs689466 and G-765C (rs20417 in the promoter region, and the COX-2 T8473C (rs5275 polymorphisms in the 3'-untranslated region. The polymorphisms were assessed together with lifestyle factors in a nested case-cohort study of 359 cases and a random cohort sample of 765 participants from the Danish prospective Diet, Cancer and Health study. Results Carriers of the variant allele of MDR1 intron 3 polymorphism were at 1.52-fold higher risk of CRC than homozygous wild type allele carriers (Incidence rate ratio (IRR = 1.52, 95% Confidence Interval (CI: 1.12-2.06. Carriers of the variant allele of MDR1 C3435T exon 26 had a lower risk of CRC than homozygous C-allele carriers (IRR = 0.71 (CI:0.50-1.00. There was interaction between these MDR1 polymorphisms and intake of red and processed meat in relation to CRC risk. Homozygous MDR1 C3435T C-allele carriers were at 8% increased risk pr 25 gram meat per day (CI: 1.00-1.16 whereas variant allele carriers were not at increased risk (p for interaction = 0.02. COX-2 and BCRP polymorphisms were not associated with CRC risk. There was interaction between NSAID use and MDR1 C3435T and COX-2 T

Polymorphisms in the xenobiotic transporter Multidrug Resistance 1 (MDR1) and interaction with meat intake in relation to risk of colorectal cancer in a Danish prospective case-cohort study

International Nuclear Information System (INIS)

Andersen, Vibeke; Østergaard, Mette; Christensen, Jane; Overvad, Kim; Tjønneland, Anne; Vogel, Ulla

2009-01-01

The xenobiotic transporters, Multidrug Resistance 1 (MDR1/ABCB1) and Breast Cancer Resistance Protein (BCRP/ABCG2) may restrict intestinal absorption of various carcinogens, including heterocyclic amines (HCA) and polycyclic aromatic hydrocarbons (PAH). Cyclooxygenase-2 (COX-2) derived prostaglandins promote gastrointestinal carcinogenesis, affecting angiogenesis, apoptosis, and invasiveness. The aim of this study was to investigate if polymorphisms in these genes were associated with risk of colorectal cancer (CRC), and to investigate possible interactions with lifestyle factors such as smoking, meat consumption, and NSAID use. The following polymorphisms were analyzed; a synonymous MDR1 C3435T (rs1045642) in exon26, G-rs3789243-A in intron3, the functional BCRP C421A (rs2231142), the two COX-2 A-1195G (rs689466) and G-765C (rs20417) in the promoter region, and the COX-2 T8473C (rs5275) polymorphisms in the 3'-untranslated region. The polymorphisms were assessed together with lifestyle factors in a nested case-cohort study of 359 cases and a random cohort sample of 765 participants from the Danish prospective Diet, Cancer and Health study. Carriers of the variant allele of MDR1 intron 3 polymorphism were at 1.52-fold higher risk of CRC than homozygous wild type allele carriers (Incidence rate ratio (IRR) = 1.52, 95% Confidence Interval (CI): 1.12-2.06). Carriers of the variant allele of MDR1 C3435T exon 26 had a lower risk of CRC than homozygous C-allele carriers (IRR = 0.71 (CI:0.50-1.00)). There was interaction between these MDR1 polymorphisms and intake of red and processed meat in relation to CRC risk. Homozygous MDR1 C3435T C-allele carriers were at 8% increased risk pr 25 gram meat per day (CI: 1.00-1.16) whereas variant allele carriers were not at increased risk (p for interaction = 0.02). COX-2 and BCRP polymorphisms were not associated with CRC risk. There was interaction between NSAID use and MDR1 C3435T and COX-2 T8473C (p-values for interaction 0

Methylenetetrahydrofolate reductase polymorphisms and interaction with smoking and alcohol consumption in lung cancer risk: a case-control study in a Japanese population.

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Kiyohara, Chikako; Horiuchi, Takahiko; Takayama, Koichi; Nakanishi, Yoichi

2011-10-25

Cigarette smoking is an established risk factor of lung cancer development while the current epidemiological evidence is suggestive of an increased lung cancer risk associated with alcohol consumption. Dietary folate, which is present in a wide range of fresh fruits and vegetables, may be a micronutrient that has a beneficial impact on lung carcinogenesis. Methylenetetrahydrofolate reductase (MTHFR) plays a crucial role in regulating folate metabolism, which affects both DNA synthesis/repair and methylation. We examined if smoking or alcohol consumption modify associations between MTHFR polymorphisms and lung cancer risk. We evaluated the role of the MTHFR C677T (rs1801133) and A1298C (rs1801131) polymorphisms in a case-control study comprised of 462 lung cancer cases and 379 controls in a Japanese population. Logistic regression was used to assess the adjusted odds ratios (OR) and 95% confidence intervals (95% CI). The TT genotype of the C677T polymorphism was significantly associated with an increased risk of lung cancer (OR = 2.27, 95% CI = 1.42 - 3.62, P fashion. The highest risks were seen for 677TT-carriers with a history of smoking or excessive drinking (OR = 6.16, 95% CI = 3.48 - 10.9 for smoking; OR = 3.09, 95% CI = 1.64 - 5.81 for drinking) compared with C-carriers without a history of smoking or excessive drinking, but no interactions were seen. The 1298CC genotype was only associated with increased risk among non-smokers (P < 0.05), and smoking was only associated with increased risks among 1298A-carriers (P < 0.01), but no significant interaction was seen. There was a synergistic interaction between the A1298C polymorphism and drinking (P < 0.05). The highest risk was seen for the CC-carriers with excessive drinking (OR = 7.24, 95% CI = 1.89 - 27.7) compared with the A-carriers without excessive drinking). The C677T polymorphism was significantly associated with lung cancer risk. Although the A1298C polymorphism was not associated with lung cancer risk

Associations between ghrelin and ghrelin receptor polymorphisms and cancer in Caucasian populations: a meta-analysis.

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Pabalan, Noel A; Seim, Inge; Jarjanazi, Hamdi; Chopin, Lisa K

2014-11-07

There is growing evidence that the ghrelin axis, including ghrelin (GHRL) and its receptor, the growth hormone secretagogue receptor (GHSR), play a role in cancer progression. Ghrelin gene and ghrelin receptor gene polymorphisms have been reported to have a range of effects in cancer, from increased risk, to protection from cancer, or having no association. In this study we aimed to clarify the role of ghrelin and ghrelin receptor polymorphisms in cancer by performing a meta-analysis of published case-control studies. In the overall analysis, homozygous and recessive associations indicated that the minor alleles of rs696217 and rs2075356 GHRL polymorphisms conferred reduced cancer risk (odds ratio [OR] 0.61-0.78). The risk was unchanged for breast cancer patients when analysed separately (OR 0.73-0.83). In contrast, the rs4684677 GHRL and the rs572169 GHSR polymorphisms conferred increased breast cancer risk (OR 1.97-1.98, p = 0.08 and OR 1.42-1.43, p = 0.08, respectively). All dominant and co-dominant effects showed null effects (OR 0.96-1.05), except for the rs572169 co-dominant effect, with borderline increased risk (OR 1.08, p = 0.05). This study suggests that the rs696217 and rs2075356 ghrelin gene (GHRL) polymorphisms may protect carriers against breast cancer, and the rs4684677 GHRL and rs572169 GHSR polymorphisms may increase the risk among carriers. In addition, larger studies are required to confirm these findings.

Association between IGF2BP2 Polymorphisms and Type 2 Diabetes Mellitus: A Case–Control Study and Meta-Analysis

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Ping Rao

2016-06-01

Full Text Available Background: Genome-wide association studies (GWAS found that IGF2BP2 rs4402960 and rs1470579 polymorphisms were associated with type 2 diabetes mellitus (T2DM risk. Many studies have replicated this association, but yielded inconsistent results. Materials and Methods: A case-control study consisting of 461 T2DM patients and 434 health controls was conducted to detect the genetic susceptibility of IGF2BP2 in a northern Han Chinese population. A meta-analysis was to evaluate the association more precisely in Asians. Results: In the case-control study, the carriers of TT genotype at rs4402960 had a higher T2DM risk than the G carriers (TG + GG (adjusted odd ratio (AOR = 1.962, 95% confidence interval (95% CI = 1.065–3.612, p = 0.031]; CC carriers at rs1470579 were more susceptible to T2DM than A carriers (CA + AA (AOR = 2.014, 95% CI = 1.114–3.642, p = 0.021. The meta-analysis containing 36 studies demonstrated that the two polymorphisms were associated with T2DM under the allele comparison, genetic models of dominant and recessive in Asians (p < 0.05. The rs4402960 polymorphisms were significantly associated with the T2DM risk after stratification by diagnostic criterion, size of sample and average age and BMI of cases, while there’re no consistent results for rs1470579. Conclusions: Our data suggests that IGF2BP2 polymorphisms are associated with T2DM in Asian populations.

Lack of neural compensatory mechanisms of BDNF val66met met carriers and APOE E4 carriers in healthy aging, mild cognitive impairment, and Alzheimer's disease.

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Gomar, Jesus J; Conejero-Goldberg, Concepcion; Huey, Edward D; Davies, Peter; Goldberg, Terry E

2016-03-01

Compromises in compensatory neurobiologic mechanisms due to aging and/or genetic factors (i.e., APOE gene) may influence brain-derived neurotrophic factor (BDNF) val66met polymorphism effects on temporal lobe morphometry and memory performance. We studied 2 cohorts from Alzheimer's Disease Neuroimaging Initiative: 175 healthy subjects and 222 with prodromal and established Alzheimer's disease. Yearly structural magnetic resonance imaging and cognitive performance assessments were carried out over 3 years of follow-up. Both cohorts had similar BDNF Val/Val and Met allele carriers' (including both Val/Met and Met/Met individuals) distribution. In healthy subjects, a significant trend for thinner posterior cingulate and precuneus cortices was detected in Met carriers compared to Val homozygotes in APOE E4 carriers, with large and medium effect sizes, respectively. The mild cognitive impairment/Alzheimer's disease cohort showed a longitudinal decline in entorhinal thickness in BDNF Met carriers compared to Val/Val in APOE E4 carriers, with effect sizes ranging from medium to large. In addition, an effect of BDNF genotype was found in APOE E4 carriers for episodic memory (logical memory and ADAS-Cog) and semantic fluency measures, with Met carriers performing worse in all cases. These findings suggest a lack of compensatory mechanisms in BDNF Met carriers and APOE E4 carriers in healthy and pathological aging. Copyright © 2016 Elsevier Inc. All rights reserved.

Paraoxonase (PON1 and PON3 polymorphisms: impact on liver expression and atorvastatin-lactone hydrolysis

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Stephan eRiedmaier

2011-07-01

Full Text Available Atorvastatin δ-lactone, a major, pharmacologically inactive metabolite, has been associated with toxicity. In a previous study we showed that polymorphisms of UGT1A3 influence atorvastatin δ-lactone formation. Here we investigated the reverse reaction, atorvastatin δ-lactone hydrolysis, in a human liver bank. Screening of microarray data revealed paraoxonases PON1 and PON3 among 17 candidate esterases. Microsomal δ-lactone hydrolysis was significantly correlated to PON1 and PON3 protein (rs=0.60; rs=0.62, respectively; P<0.0001. PON1 and PON3 were strongly correlated to each other (rs=0.60 but PON1 was shown to be more extensively glycosylated than PON3. In addition a novel splice variant of PON3 was identified. Genotyping of 40 polymorphisms within the PON-locus identified PON1 promoter polymorphisms (-108T>C, -832G>A, -1741G>A and a tightly linked group of PON3 polymorphisms (-4984A>G, -4105G>A, -1091A>G, -746C>T and F21F to be associated with changes in atorvastatin δ-lactone hydrolysis and expression of PON1 but not PON3. However, carriers of the common PON1 polymorphisms L55M or Q192R showed no difference in δ-lactone hydrolysis or PON expression. Haplotype analysis revealed decreased δ-lactone hydrolysis in carriers of the most common haplotype *1 compared to carriers of haplotypes *2, *3, *4 and *7. Analysis of non-genetic factors showed association of hepatocellular and cholangiocellular carcinoma with decreased PON1 and PON3 expression, respectively. Increased C-reactive protein and γ-glutamyl transferase levels were associated with decreased protein expression of both enzymes, and increased bilirubin levels, cholestasis and pre-surgical exposure to omeprazole or pantoprazole were related to decreased PON3 protein. In conclusion, PON-locus polymorphisms affect PON1 expression whereas non-genetic factors have an effect on PON1 and PON3 expression. This may influence response to therapy or adverse events in statin treatment.

Aggression and 5HTT polymorphism in females: study of synchronized swimming and control groups.

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Sysoeva, Olga V; Maluchenko, Natalia V; Timofeeva, Marina A; Portnova, Galina V; Kulikova, Maria A; Tonevitsky, Alexandr G; Ivanitsky, Alexey M

2009-05-01

Aggression is a heterogeneous heritable psychological trait, also influenced by environmental factors. Previous studies, mostly conducted on male population, have found some associations of the aggression with the polymorphisms of genes, regulating the activity of serotonin (5-HT) in the brain. However, psychological as well as biochemical manifestations of the aggression are different in males and females. Our study aimed to investigate the association of 5-HTT gene polymorphism with different facets of aggression (BDHI) in females. Two groups: the synchronized swimming and non-athlete control, - were examined to study the possible modulation effect of sport on the association between 5-HTT gene polymorphism and aggression. It was found that in both groups the low-active 5-HTT polymorphism (SS) was associated with increased scores on Indirect Hostility scale and decreased scores on Negativism scale, compared to LL genotype. No interaction effect between sport and 5-HTT polymorphism was found. The higher percentage of LL-carriers and lower of LS-carriers in the synchronized swimming group compared to the control one was observed. This may be the sign of the importance of LL polymorphism of 5-HTT gene, previously associated with higher resistance to stress factors, for being an athlete, although this result has to be taken cautiously keeping in mind the stratification problem. Synchronized swimmers had lower scores on Assault, Negativism, Irritability and Verbal Hostility compared to age-matched control girls (in general and for each 5-HTT genotype separately), suggesting that they may have more matured emotional system (older control group has also lower scores on these scales).

Methionine synthase A2756G and reduced folate carrier1 A80G ...

African Journals Online (AJOL)

Maha Moustafa

2015-10-09

Oct 9, 2015 ... folate carrier (RFC1) A80G gene polymorphisms on the maternal risk for DS. Patients: This ... Peer review under responsibility of Ain Shams University. ... Folate is the general term for a water-soluble B vitamin (vita- min B9) ...

Downregulation of reversion-inducing cysteine-rich protein with Kazal motifs in malignant melanoma: inverse correlation with membrane-type 1-matrix metalloproteinase and tissue inhibitor of metalloproteinase 2.

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Jacomasso, Thiago; Trombetta-Lima, Marina; Sogayar, Mari C; Winnischofer, Sheila M B

2014-02-01

The invasive phenotype of many tumors is associated with an imbalance between the matrix metalloproteinases (MMPs) and their inhibitors, tissue inhibitors of metalloproteinases (TIMPs), and the membrane-anchored reversion-inducing cysteine-rich protein with Kazal motifs (RECK). RECK inhibits MMP-2, MMP-9, and MT1-MMP, and has been linked to patient survival and better prognosis in several types of tumors. However, despite the wide implication of these MMPs in melanoma establishment and progression, the role of RECK in this type of tumor is still unknown. Here, we analyzed the expression of RECK, TIMP1, TIMP2, TIMP3, MT1MMP, MMP2, and MMP9 in two publicly available melanoma microarray datasets and in a panel of human melanoma cell lines. We found that RECK is downregulated in malignant melanoma, accompanied by upregulation of MT1MMP and TIMP2. In both datasets, we observed that the group of samples displaying higher RECK levels show lower median expression levels of MT1MMP and TIMP2 and higher levels of TIMP3. When tested in a sample-wise manner, these correlations were statistically significant. Inverse correlations between RECK, MT1MMP, and TIMP2 were verified in a panel of human melanoma cell lines and in a further reduced model that includes a pair of matched primary tumor-derived and metastasis-derived cell lines. Taken together, our data indicate a consistent correlation between RECK, MT1MMP, and TIMP2 across different models of clinical samples and cell lines and suggest evidence of the potential use of this subset of genes as a gene signature for diagnosing melanoma.

Association of aromatase (TTTA)n repeat polymorphisms with central precocious puberty in girls.

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Lee, Hae Sang; Kim, Kyung Hee; Hwang, Jin Soon

2014-09-01

Precocious puberty is characterized by early activation of the pituitary-gonadal axis. Oestrogen is the final key factor to start the onset of puberty. The cytochrome P450 19A1 (CYP19A1) gene encodes an aromatase that is responsible for the conversion of androgens to oestrogen, which is a key step in oestrogen biosynthesis. The aim of this study was to identify CYP19A1 gene mutations or polymorphisms in girls with central precocious puberty (CPP). We evaluated the frequency of allelic variants of the CYP19A1 exons and the tetranucleotide tandem repeat (TTTA)n in intron 4 in 203 idiopathic central precocious puberty (CPP) girls and 101 normal healthy women. The genotype analysis of the CYP19A1 (TTTA)n polymorphism revealed six different alleles ranging from seven to 13 repeats. Among the six different repeat alleles detected in this study, the (TTTA)₁₃ repeat allele was only detected in the patient group and carriers of the (TTTA)₁₃ allele were significantly associated with an increased risk of CPP (OR = 1·509, 95% CI = 1·425-1·598, P = 0·033). Carriers of the (TTTA)₁₃ repeat allele were significantly younger at pubertal onset and had higher levels of oestrogen than noncarriers of the (TTTA)₁₃ repeat allele. Although nine polymorphisms were detected in exons of the CYP19A1 gene, no clinical significance was observed. In this study, carriers of a higher repeat (TTTA)₁₃ polymorphism in intron 4 of the CYP19A1 gene had higher levels of oestrogen. Those carrying the (TTTA)₁₃ repeat allele may have a higher risk of developing CPP. © 2014 John Wiley & Sons Ltd.

Genetic polymorphisms associated to folate transport as predictors of increased risk for acute lymphoblastic leukemia in Mexican children

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Fausto Zaruma-Torres

2016-08-01

Full Text Available Acute lymphoblastic leukemia (ALL is a frequent neoplasia occurring in children. The most commonly used drug for the treatment of ALL is methotrexate (MTX, an anti-folate agent. Previous studies suggest that folate transporters play a role in ALL prognosis and that genetic polymorphism of genes encoding folate transporters may increase the risk of ALL. Therefore, the main goal of this study was to determine the associations among six genetic polymorphisms in four genes related with the folate transporter pathway to determine a relationship with the occurrence of ALL in Mexican children.A case-control study was performed in 73 ALL children and 133 healthy children from Northern and Northwestern Mexico. COL18A1 (rs2274808, SLC19A1 (rs2838956, ABCB1 (rs1045642 and rs1128503 and ABCC5 (rs9838667 and rs3792585. polymorphisms were assayed through qPCR.Our results showed an increased ALL risk in children carrying CT genotype (OR=2.55, CI 95% 1.11-5.83, p=0.0001 and TT genotype (OR=21.05, CI 95% 5.62-78.87, p<0.0001 of COL18A1 rs2274808; in SLC19A1 rs2838956 AG carriers (OR=44.69, CI 95% 10.42-191.63, p=0.0001; in ABCB1 rs1045642 TT carriers (OR=13.76, CI 95% 5.94-31.88, p=0.0001; in ABCC5 rs9838667 AC carriers (OR=2.61, CI 95% 1.05-6.48, p<0.05; and in ABCC5 rs3792585 CC carriers (OR=9.99, CI 95% 3.19-31.28, p=0.004. Moreover, several combinations of genetic polymorphisms were found to be significantly associated with a risk for ALL. Finally, two combinations of ABCC5 polymorphisms resulted in protection from this neoplasia.In conclusion, certain genetic polymorphisms related to the folate transport pathway, particularly COL18A1 rs2274808, SLC19A1 rs2838956, ABCB1 rs1045642 and ABCC5 rs3792585, were associated with an increased risk for ALL in Mexican children.

Methionine synthase A2756G and reduced folate carrier1 A80G ...

African Journals Online (AJOL)

Background: Polymorphisms of genes encoding enzymes involved in folate metabolism have long been hypothesized to be maternal risk factors for Down syndrome, however, results are conflicting and inconclusive. Aim of the study: To analyze the effect of methionine synthase (MTR) A2756G, and reduced folate carrier ...

APOE and CETP TaqIB polymorphisms influence metabolic responses to Hibiscus sabdariffa L. and Gynostemma pentaphyllum Makino tea consumption in hypercholesterolemic subjects.

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Jeenduang, Nutjaree; Sangkaew, Boonnisa; Chantaracha, Pacharee; Chanchareonsri, Sirada; Plyduang, Thunyaluk; Thitdee, Wanida; Samae, Cathaleeya; Pitumanon, Wacharaporn

2017-03-01

Hibiscus sabdariffa L. (HS) and Gynostemma pentaphyllum Makino (GP) have been used as traditional medicines to treat diabetes and hypercholesterolemia. Nevertheless, there is interindividual variation in the metabolic responses to HS and GP consumption. This may be due to genetic factors. The aim of this study was to investigate the effects of HS and GP tea consumption on anthropometric data, fasting blood glucose (FBG), and lipid concentrations in hypercholesterolemia subjects with different genotypes of the APOE and CETP TaqIB polymorphisms. Forty-eight subjects with hypercholesterolemia were given either HS or GP tea for 30 days. Anthropometric and biochemical variables were determined, and APOE and CETP TaqIB polymorphisms were analyzed using the polymerase chain reaction- restriction fragment length polymorphism (PCR-RFLP). E4 (p=0.008) and homozygous B1B1 (p=0.010) carriers had significantly decreased HDL-C concentrations after HS consumption; in addition, B2 carriers who consumed HS showed significantly decreased triglyceride (TG) concentrations (p=0.039). Regarding GP consumption, non-E4 carriers had significantly decreased HDL-C (p=0.009) and FBG (p=0.042) concentrations. Furthermore, B2 carriers had significantly decreased total cholesterol (TC) (p=0.045), HDL-C (p=0.004), and FBG (p=0.026) concentrations. HS consumption may have beneficial effects with respect to TG concentrations in the B2 carriers, but it may adversely affect HDL-C concentrations in homozygous B1B1 and E4 carriers. In contrast, GP consumption may have favorable effects on TC and FBG concentrations but not on HDL-C concentrations for B2 and/or non-E4 carriers.

[Association between VDR gene polymorphisms and HOMA index for prediabetes in Ningxia].

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Liao, Sha; He, Jun; Li, Xiaoxia; Xu, Honexia; Liu, Xiuying; Zhao, Yi; Zhang, Yuhong

2016-03-01

To explore the association between the vitamin D receptor (VDR) gene polymorphisms and HOMA index in prediabetes. On the basis of a cross-sectional study which was conducted in Ningxia during 2008-2012, 339 controls and 468 subjects with prediabetes were selected according to ADA diabetes diagnosis standards. Anthropometric data and blood samples were collected in the field investigation. Blood biochemistry analyses and insulin determination were carried out in the laboratory. The whole blood DNA was extracted for genotyping. The BMI, WC, FPG and HOMA-IR of individuals with prediabetes were higher than those of the controls, while the HOMA-B and HOMA-S in cases were lower than those of the controls (P HOMA-B than bb carrier, and they showed significantly higher HOMA-S than bb carriers (P HOMA-B index was the risk factor of prediabetes in individuals who carried genotype BB/Bb for BsmI and genotype FF/Ff/ff for FokI (OR > 1 , P HOMA-S and HOM-IR were also the risk factors of prediabetes (OR > 1, P HOMA index in prediabetes. The BsmI polymorphism seemed to influence HOMA-B, while the FokI polymorphism influence HOMA-B and HOMA-IR at different levels.

Face and emotion expression processing and the serotonin transporter polymorphism 5-HTTLPR/rs22531.

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Hildebrandt, A; Kiy, A; Reuter, M; Sommer, W; Wilhelm, O

2016-06-01

Face cognition, including face identity and facial expression processing, is a crucial component of socio-emotional abilities, characterizing humans as highest developed social beings. However, for these trait domains molecular genetic studies investigating gene-behavior associations based on well-founded phenotype definitions are still rare. We examined the relationship between 5-HTTLPR/rs25531 polymorphisms - related to serotonin-reuptake - and the ability to perceive and recognize faces and emotional expressions in human faces. For this aim we conducted structural equation modeling on data from 230 young adults, obtained by using a comprehensive, multivariate task battery with maximal effort tasks. By additionally modeling fluid intelligence and immediate and delayed memory factors, we aimed to address the discriminant relationships of the 5-HTTLPR/rs25531 polymorphisms with socio-emotional abilities. We found a robust association between the 5-HTTLPR/rs25531 polymorphism and facial emotion perception. Carriers of two long (L) alleles outperformed carriers of one or two S alleles. Weaker associations were present for face identity perception and memory for emotional facial expressions. There was no association between the 5-HTTLPR/rs25531 polymorphism and non-social abilities, demonstrating discriminant validity of the relationships. We discuss the implications and possible neural mechanisms underlying these novel findings. © 2016 John Wiley & Sons Ltd and International Behavioural and Neural Genetics Society.

Genetic polymorphisms of surfactant protein D rs2243639, Interleukin (IL)-1β rs16944 and IL-1RN rs2234663 in chronic obstructive pulmonary disease, healthy smokers, and non-smokers.

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Issac, Marianne Samir M; Ashur, Wafaa; Mousa, Heba

2014-06-01

Chronic obstructive pulmonary disease (COPD) is a complex chronic inflammatory disease that involves the activity of various inflammatory cells and mediators. It has been suggested that susceptibility to COPD is, at least in part, genetically determined. The primary aim of this study was to investigate the association between surfactant protein D (SFTPD) rs2243639, interleukin (IL)-1β rs16944 and IL-1 receptor antagonist (IL-1RN) rs2234663 gene polymorphisms and COPD susceptibility, as well as examining the association between the various IL-1RN/IL-1β haplotypes and pulmonary function tests (PFT). Secondly, we aimed to examine the influence of SFTPD rs2243639 polymorphism on serum surfactant protein D (SP-D) level. A total of 114 subjects were recruited in this study and divided into three groups: 63 COPD patients, 25 asymptomatic smokers, and 26 healthy controls. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was performed for the detection of SFTPD rs2243639 and IL-1β rs16944 polymorphisms. Detection of variable numbers of an 86-bp tandem repeat (VNTR) of IL-1RN was done using PCR. Serum SP-D level was measured using enzyme linked-immunosorbent assay. PFTs were measured by spirometry. Carriers of the SFTPD AG and AA polymorphic genotypes constituted 71.4 % of COPD patients versus 48 % in asymptomatic smokers, with a statistically significant difference between the two groups (p = 0.049). Smokers who were carriers of the polymorphic SFTPD rs2243639 A allele (AG and AA genotypes) have a 2.708 times risk of developing COPD when compared with wild-type GG genotype carriers [odds ratio (OR) 2.708 (95 % CI 1.041-7.047)]. Forced expiratory flow (FEF) 25-75 % predicted was higher in IL-1RN*1/*1 when compared with *1/*2 (p = 0.013). FEF25-75 % predicted in carriers of haplotype IL-1RN *1/IL-1β T (49.21 ± 10.26) was statistically significantly higher than in carriers of IL-1RN *2/IL-1β T (39.67 ± 12.64) [p = 0

AMPD1 polymorphism and response to regadenoson.

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Saab, Rayan; Zouk, Aline N; Mastouri, Ronald; Skaar, Todd C; Philips, Santosh; Kreutz, Rolf P

2015-11-01

 AMPD1 c.34C > T (rs17602729) polymorphism results in AMPD1 deficiency. We examined the association of AMPD1 deficiency and variability of hemodynamic response to regadenoson. Genotyping for c.34C>T was performed in 267 patients undergoing regadenoson cardiac stress testing. Carriers of c.34C >T variant exhibited higher relative changes in systolic blood pressure (SBP) compared with wild-type subjects ([%] SBP change to peak: 12 ± 25 vs 5 ± 13%; p = 0.01) ([%] SBP change to nadir: -3 ± 15 vs -7 ± 11%; p = 0.04). Change in heart rate was similar between groups, but side effects were more common in carriers of the variant (+LR = 4.2; p = 0.04). AMPD1 deficiency may be involved in the modulation of regadenoson's systemic effects.

The association of reduced folate carrier 80G>A polymorphism to outcome in childhood acute lymphoblastic leukemia interacts with chromosome 21 copy number

DEFF Research Database (Denmark)

Gregers, Jannie; Christensen, Ib Jarle; Dalhoff, Kim

2010-01-01

with chromosome 21 copy number in the leukemic clone. A total of 500 children with acute lymphoblastic leukemia treated according to the common Nordic treatment protocols were included, and we found that the RFC AA variant was associated with a 50% better chance of staying in remission compared with GG or GA......The reduced folate carrier (RFC) is involved in the transport of methotrexate (MTX) across the cell membrane. The RFC gene (SLC19A1) is located on chromosome 21, and we hypothesized that the RFC80 G>A polymorphism would affect outcome and toxicity in childhood leukemia and that this could interact...... variants (P = .046). Increased copy numbers of chromosome 21 appear to improve outcome also in children with GA or GG variant. In a subset of 182 children receiving 608 high-dose MTX courses, we observed higher degree of bone marrow toxicity in patients with the RFC AA variant compared with GA/GG variants...

Polymorphisms of the OXTR gene explain why sales professionals love to help customers

NARCIS (Netherlands)

W.J.M.I. Verbeke (Willem); R.P. Bagozzi (Richard); W.E. van den Berg (Wouter); A. Lemmens (Aurélie)

2013-01-01

textabstractPolymorphisms of the OXTR gene affect people's social interaction styles in various social encounters: carriers of the OXTR GG, compared to the OXTR AA/AG in general, are more motivated to interact socially and detect social salience. We focus on sales professionals operating in

Effects of VKORC1 Genetic Polymorphisms on Warfarin Maintenance Dose Requirement in a Chinese Han Population

Science.gov (United States)

Yan, Xiaojuan; Yang, Feng; Zhou, Hanyun; Zhang, Hongshen; Liu, Jianfei; Ma, Kezhong; Li, Yi; Zhu, Jun; Ding, Jianqiang

2015-01-01

Background VKORC1 is reported to be capable of treating several diseases with thrombotic risk, such as cardiac valve replacement. Some single-nucleotide polymorphisms (SNPs) in VKORC1 are documented to be associated with clinical differences in warfarin maintenance dose. This study explored the correlations of VKORC1–1639 G/A, 1173 C/T and 497 T/G genetic polymorphisms with warfarin maintenance dose requirement in patients undergoing cardiac valve replacement. Material/Methods A total of 298 patients undergoing cardiac valve replacement were recruited. During follow-up, clinical data were recorded. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method was applied to detect VKORC1–1639 G/A, 1173 C/T and 497 T/G polymorphisms, and genotypes were analyzed. Results Correlations between warfarin maintenance dose and baseline characteristics revealed statistical significances of age, gender and operation methods with warfarin maintenance dose (all PWarfarin maintenance dose in VKORC1–1639 G/A AG + GG carriers was obviously higher than in AA carriers (Pwarfarin maintenance dose was apparently higher in patients with CT genotype (Pwarfarin maintenance dose (all Pwarfarin maintenance dose in patients undergoing cardiac valve replacement; meanwhile, gender, operation method and method for heart valve replacement might also be correlate with warfarin maintenance dose. PMID:26583785

The polymorphism IL-1 beta T-31C is associated with a longer overall survival in patients with multiple myeloma undergoing auto-SCT

DEFF Research Database (Denmark)

Vangsted, A.J.; Klausen, T.W.; Ruminski, W.

2009-01-01

high-dose melphalan treatment followed by Auto-SCT and examined the influence of single nucleotide polymorphisms (SNPs) in genes involved in the inflammatory response. We found that the polymorphism IL-1 beta T-31C significantly influenced overall survival (OS; P = 0.02) and that carriers...

IFNGR2 genetic polymorphism associated with sex-specific paranoid schizophrenia risk.

Science.gov (United States)

Jemli, Achraf; Inoubli, Oumaima; Trifa, Fatma; Mechri, Anouar; Zaafrane, Ferid; Gaha, Lotfi; Jrad, Besma Bel Hadj

2017-01-01

Considering current scientific evidence about the significant role of chronic low grade inflammation in the physiopathology of schizophrenia, it has been hypothesized that changes in pro-inflammatory cytokines such as interferon gamma may have a significant role in the predisposition to schizophrenia. This study focuses on identifying whether the functional polymorphism of interferon gamma receptor 2 (IFNGR2) is a risk factor for the development of schizophrenia. This study was conducted by the RFLP-PCR on a Tunisian population composed of 225 patients with different sub-types of schizophrenia and 166 controls. The IFNGR2 (Q64R) polymorphism analysis showed higher frequencies of minor homozygous genotype (RR) and allele (R) in all patients compared to controls (21.8% vs 10.2%; p = .006, OR = 2.54) and (44% vs 34.9%; p = .01; OR = 1.46), respectively. This correlation was confirmed only for males. This study also noted a significant increase of the mutated homozygous (RR) genotype and (R) allele frequencies of IFNGR2 in paranoid schizophrenics compared to controls (31.4% vs 10.2%; p = .001; OR = 3.34 and 47.2% vs 34.9%; p = .009; OR = 1.66, respectively). This increase remains significant after using binary logistic regression to eliminate confounding factors such as age and sex. Additionally, carriers of RR genotype have significant lower scores on the Scale of Assessment of Positive (SAPS) and negative (SANS) symptoms comparatively to the carrier of the QQ + QR genotypes, suggesting that the R recessive allele carriers could have milder symptoms. The IFNGR2Q64R polymorphism is correlated with male sex and paranoid schizophrenia. It is suggested that a chronic neuroinflammation may predispose to the paranoid schizophrenia development in men.

FKBP5 polymorphisms influence pre-learning stress-induced alterations of learning and memory.

Science.gov (United States)

Zoladz, Phillip R; Dailey, Alison M; Nagle, Hannah E; Fiely, Miranda K; Mosley, Brianne E; Brown, Callie M; Duffy, Tessa J; Scharf, Amanda R; Earley, McKenna B; Rorabaugh, Boyd R

2017-03-01

FK506 binding protein 51 (FKBP5) is a co-chaperone of heat shock protein 90 and significantly influences glucocorticoid receptor sensitivity. Single nucleotide polymorphisms (SNPs) in the FKBP5 gene are associated with altered hypothalamus-pituitary-adrenal (HPA) axis function, changes in the structure and function of several cognitive brain areas, and increased susceptibility to post-traumatic stress disorder, major depression, bipolar disorder and suicidal events. The mechanisms underlying these associations are largely unknown, but it has been speculated that the influence of these SNPs on emotional memory systems may play a role. In the present study, 112 participants were exposed to the socially evaluated cold pressor test (stress) or control (no stress) conditions immediately prior to learning a list of 42 words. Participant memory was assessed immediately after learning (free recall) and 24 h later (free recall and recognition). Participants provided a saliva sample that enabled the genotyping of three FKBP5 polymorphisms: rs1360780, rs3800373 and rs9296158. Results showed that stress impaired immediate recall in risk allele carriers. More importantly, stress enhanced long-term recall and recognition memory in non-carriers of the risk alleles, effects that were completely absent in risk allele carriers. Follow-up analyses revealed that memory performance was correlated with salivary cortisol levels in non-carriers, but not in carriers. These findings suggest that FKBP5 risk allele carriers may possess a sensitized stress response system, perhaps specifically for stress-induced changes in corticosteroid levels, which might aid our understanding of how SNPs in the FKBP5 gene confer increased risk for stress-related psychological disorders and their related phenotypes. © 2016 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

Role of Key TYMS Polymorphisms on Methotrexate Therapeutic Outcome in Portuguese Rheumatoid Arthritis Patients

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Lima, Aurea; Seabra, Vítor; Bernardes, Miguel; Azevedo, Rita; Sousa, Hugo; Medeiros, Rui

2014-01-01

Background Therapeutic outcome of rheumatoid arthritis (RA) patients treated with methotrexate (MTX) can be modulated by thymidylate synthase (TS) levels, which may be altered by genetic polymorphisms in TS gene (TYMS). This study aims to elucidate the influence of TYMS polymorphisms in MTX therapeutic outcome (regarding both clinical response and toxicity) in Portuguese RA patients. Methods Clinicopathological data from 233 Caucasian RA patients treated with MTX were collected, outcomes were defined and patients were genotyped for the following TYMS polymorphisms: 1) 28 base pairs (bp) variable number tandem repeat (rs34743033); 2) single nucleotide polymorphism C>G (rs2853542); and 3) 6 bp sequence deletion (1494del6, rs34489327). Chi-square and binary logistic regression analyses were performed, using genotype and haplotype-based approaches. Results Considering TYMS genotypes, 3R3R (p = 0.005, OR = 2.34), 3RC3RG (p = 0.016, OR = 3.52) and 6bp− carriers (p = 0.011, OR = 1.96) were associated with non-response to MTX. Multivariate analysis confirmed the increased risk for non-response to MTX in 6bp− carriers (p = 0.016, OR = 2.74). Data demonstrated that TYMS polymorphisms were in linkage disequilibrium (p<0.00001). Haplotype multivariate analysis revealed that haplotypes harboring both 3R and 6bp− alleles were associated with non-response to MTX. Regarding MTX-related toxicity, no statistically significant differences were observed in relation to TYMS genotypes and haplotypes. Conclusion Our study reveals that TYMS polymorphisms could be important to help predicting clinical response to MTX in RA patients. Despite the potential of these findings, translation into clinical practice needs larger studies to confirm these evidences. PMID:25279663

The N363S polymorphism of the glucocorticoid receptor and metabolic syndrome factors in men

DEFF Research Database (Denmark)

Buemann, Benjamin; Black, Eva; Holst, Claus

2005-01-01

with the obese men (n = 299; age, 50 +/- 7 years). The subjects were genotyped for the N363S polymorphism by polymerase chain reaction-restriction fragment length polymorphism. Body composition was measured by DXA. Glucose metabolism was evaluated by an oral glucose tolerance test, and the Matsudas index...... was calculated as a proxy for insulin sensitivity. Serum triglycerides and total and high-density lipoprotein-cholesterol were measured in the fasting state. RESULTS: Among the men with juvenile-onset obesity, carriers (n = 17) of the 363S allele had a lower whole body fat percentage, after accounting...... for differences in BMI and higher Matsudas index, compared with the noncarriers. The difference in Matsudas index lost statistical significance after the difference in body fat was accounted for. In the randomly sampled men, these variables did not relate to genotype. No relationship between carriers...

Progranulin Levels in Plasma and Cerebrospinal Fluid in Granulin Mutation Carriers

Directory of Open Access Journals (Sweden)

Lieke H.H. Meeter

2016-07-01

Full Text Available Background: Pathogenic mutations in the granulin gene (GRN are causative in 5-10% of patients with frontotemporal dementia (FTD, mostly leading to reduced progranulin protein (PGRN levels. Upcoming therapeutic trials focus on enhancing PGRN levels. Methods: Fluctuations in plasma PGRN (n = 41 and its relationship with cerebrospinal fluid (CSF, n = 32 and specific single nucleotide polymorphisms were investigated in pre- and symptomatic GRN mutation carriers and controls. Results: Plasma PGRN levels were lower in carriers than in controls and showed a mean coefficient of variation of 5.3% in carriers over 1 week. Although plasma PGRN correlated with CSF PGRN in carriers (r = 0.54, p = 0.02, plasma only explained 29% of the variability in CSF PGRN. rs5848, rs646776 and rs1990622 genotypes only partly explained the variability of PGRN levels between subjects. Conclusions: Plasma PGRN is relatively stable over 1 week and therefore seems suitable for treatment monitoring of PGRN-enhancing agents. Since plasma PGRN only moderately correlated with CSF PGRN, CSF sampling will additionally be needed in therapeutic trials.

Ghrelin precursor gene polymorphism and methamphetamine dependence in the Korean population.

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Yoon, Su-Jung; Pae, Chi-Un; Lee, Heejin; Choi, Bomoon; Kim, Tae-Suk; Lyoo, In Kyoon; Kwon, Do-Hoon; Kim, Dai-Jin

2005-12-01

Ghrelin is a recently isolated brain-gut peptide that has growth hormone-releasing and appetite-inducing activities. Several recent studies have suggested that ghrelin plays a major role in the pathophysiology of drug-seeking behavior and anxiety. Therefore, we assessed the effect of the ghrelin precursor polymorphism on methamphetamine dependence in the Korean population. One hundred and eighteen patients with methamphetamine dependence, according to the Diagnostic and Statistical Manual of Mental Disorders-IV (DSM-IV) criteria, and the 144 healthy controls were enrolled in this study. Genotyping for the ghrelin precursor polymorphism was performed by the polymerase chain reaction-restriction fragment length polymorphism-based technique. The genotypic and allelic distributions of the ghrelin precursor polymorphism in the patients with methamphetamine dependence were not significantly different from those of the control subjects. However, the Met72 carriers were associated with the emotional problems of methamphetamine dependence. The patients with the Met72 allele were more depressed and anxious than the homozygous patients with the wild Leu72 allele. The present study suggests that the ghrelin precursor polymorphism may not confer a susceptibility to the development of methamphetamine dependence in the Korean population. However, the Leu72Met polymorphism could have a potential role in the emotional problems that are associated with this disease.

Role of Hyperhomocysteinemia and Methylene Tetrahydrofolate Reductase C677T Polymorphism in Idiopathic Portal Vein Thrombosis.

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Ghaznavi, Habib; Soheili, Zahra; Samiei, Shahram; Soltanpour, Mohammad Soleiman

2016-03-01

Portal vein thrombosis (PVT) is a rare and life-threatening vascular disorder characterized by obstruction or narrowing of the portal vein. Hyperhomocysteinemia and methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism has been studied in PVT patients with conflicting results. In the present study the association of hyperhomocysteinemia and MTHFR C677T polymorphism with PVT risk was investigated in Iranians. Our study population consisted of 10 idiopathic PVT patients and 80 healthy control subjects matched for age and sex. MTHFR C677T polymorphism was genotyped by the polymerase chain reaction technique combined with restriction enzyme fragment length polymorphism (PCR-RFLP) technique and plasma total homocysteine (tHcy) levels were determined by enzyme immunoassay method. Mean plasma tHcy levels were significantly higher in PVT patients (20.2±6.8) than control subjects (10.9±4.7) (P=0.001). Moreover, plasma tHcy levels were significantly higher in 677T allele carriers relative to 677C allele carriers in both PVT patients (P=0.01) and control subjects (P=0.03). Neither homozygote nor heterozygote genotypes of MTHFR C677T polymorphism correlated significantly with PVT risk (P>0.05). Moreover, MTHFR C677T polymorphism didn't increase the risk of PVT under dominant (CT+TT vs. CC) or recessive (TT vs. CC+CT) genetic models analyzed (P>0.05). The difference in frequency of minor 677T allele between PVT patients and control subjects was not statistically significant (P>0.05). Based on the current study, we suggest that hyperhomocysteinemia constitutes a significant and common risk factor for PVT. Also, MTHFR C677T polymorphism is not a risk factor for PVT but is a contributing factor for elevated plasma tHcy levels.

Understanding polymorphism in organic semiconductor thin films through nanoconfinement.

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Diao, Ying; Lenn, Kristina M; Lee, Wen-Ya; Blood-Forsythe, Martin A; Xu, Jie; Mao, Yisha; Kim, Yeongin; Reinspach, Julia A; Park, Steve; Aspuru-Guzik, Alán; Xue, Gi; Clancy, Paulette; Bao, Zhenan; Mannsfeld, Stefan C B

2014-12-10

Understanding crystal polymorphism is a long-standing challenge relevant to many fields, such as pharmaceuticals, organic semiconductors, pigments, food, and explosives. Controlling polymorphism of organic semiconductors (OSCs) in thin films is particularly important given that such films form the active layer in most organic electronics devices and that dramatic changes in the electronic properties can be induced even by small changes in the molecular packing. However, there are very few polymorphic OSCs for which the structure-property relationships have been elucidated so far. The major challenges lie in the transient nature of metastable forms and the preparation of phase-pure, highly crystalline thin films for resolving the crystal structures and evaluating the charge transport properties. Here we demonstrate that the nanoconfinement effect combined with the flow-enhanced crystal engineering technique is a powerful and likely material-agnostic method to identify existing polymorphs in OSC materials and to prepare the individual pure forms in thin films at ambient conditions. With this method we prepared high quality crystal polymorphs and resolved crystal structures of 6,13-bis(triisopropylsilylethynyl)pentacene (TIPS-pentacene), including a new polymorph discovered via in situ grazing incidence X-ray diffraction and confirmed by molecular mechanic simulations. We further correlated molecular packing with charge transport properties using quantum chemical calculations and charge carrier mobility measurements. In addition, we applied our methodology to a [1]benzothieno[3,2-b][1]1benzothiophene (BTBT) derivative and successfully stabilized its metastable form.

[Relationship between Ghrelin polymorphism and serum lipoprotein levels in Han Chinese with or without coronary heart disease risk factors].

Science.gov (United States)

Xie, Xuan; Zhang, Jing; Wang, Yu-huan; Wang, Jun-hong; Zhang, Chun-hong; Ni, Hong-yan; Yuan, Xiao-hong

2008-04-01

To investigate the relationship between polymorphism of Ghrelin gene and serum levels of lipoprotein in Han Chinese with or without coronary heart disease (CHD) risk factors. PCR restriction fragment length polymorphism assay was used to detect the distribution of genotypes of Ghrelin gene in 225 Han Chinese (40 to 69 years-old) with CHD risk factors, 78 subjects without CHD risk factors served as normal controls. Serum levels of total cholesterol (TC), triglyceride (TG), high density lipoprotein-cholesterol (HDL-C), low density lipoprotein-cholesterol (LDL-C) and very low-density lipoprotein (VLDL) were measured to analyze the relationship with the polymorphism of Ghrelin gene. Ghrelin genotype frequencies of AA, AG, GG (0.975, 0.025, 0.00 in control group and 0.956, 0.040, 0.004 in the high-risk group, all P > 0.05) as well as the allele frequencies of A, G (0.987, 0.013 in control group and 0.976, 0.024 in the high-risk group, all P > 0.05) were similar between the groups. HDL-C levels of the Arg/Gln carriers were significantly lower than those of Arg/Arg carriers in control group and in the high-risk group (all P < 0.05). Arg/Gln carriers were associated lower HDL-C levels in Han Chinese.

The BDNF-Val66Met polymorphism modulates parental rearing effects on adult psychiatric symptoms: a community twin-based study.

Science.gov (United States)

Ibarra, P; Alemany, S; Fatjó-Vilas, M; Córdova-Palomera, A; Goldberg, X; Arias, B; González-Ortega, I; González-Pinto, A; Nenadic, I; Fañanás, L

2014-06-01

To test whether firstly, different parental rearing components were associated with different dimensions of psychiatric symptoms in adulthood, secondly BDNF-Val66Met polymorphism moderated this association and thirdly, this association was due to genetic confounding. Perceived parental rearing according to Parental Bonding Instrument (PBI), psychiatric symptoms evaluated with the Brief Symptom Inventory (BSI) and the BDNF-Val66Met polymorphism were analyzed in a sample of 232 adult twins from the general population. In the whole sample, paternal care was negatively associated with depression. Maternal overprotection was positively associated with paranoid ideation, obsession-compulsion and somatization. Gene-environment interaction effects were detected between the BDNF-Val66Met polymorphism and maternal care on phobic anxiety, paternal care on hostility, maternal overprotection on somatization and paternal overprotection also in somatization. In the subsample of MZ twins, intrapair differences in maternal care were associated with anxiety, paranoid ideation and somatization. Met carriers were, in general, more sensitive to the effects of parental rearing compared to Val/Val carriers in relation to anxiety and somatization. Contra-intuitively, our findings suggest that high rates of maternal care might be of risk for Met carriers regarding anxiety. Results from analyses controlling for genetic confounding were in line with this finding. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

Effects of the BDNF Val66Met polymorphism on neural responses to facial emotion.

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Mukherjee, Prerona; Whalley, Heather C; McKirdy, James W; McIntosh, Andrew M; Johnstone, Eve C; Lawrie, Stephen M; Hall, Jeremy

2011-03-31

The brain derived neurotrophic factor (BDNF) Val66Met polymorphism has been associated with affective disorders, but its role in emotion processing has not been fully established. Due to the clinically heterogeneous nature of these disorders, studying the effect of genetic variation in the BDNF gene on a common attribute such as fear processing may elucidate how the BDNF Val66Met polymorphism impacts brain function. Here we use functional magnetic resonance imaging examine the effect of the BDNF Val66Met genotype on neural activity for fear processing. Forty healthy participants performed an implicit fear task during scanning, where subjects made gender judgments from facial images with neutral or fearful emotion. Subjects were tested for facial emotion recognition post-scan. Functional connectivity was investigated using psycho-physiological interactions. Subjects were genotyped for the BDNF Val66Met polymorphism and the measures compared between genotype groups. Met carriers showed overactivation in the anterior cingulate cortex (ACC), brainstem and insula bilaterally for fear processing, along with reduced functional connectivity from the ACC to the left hippocampus, and impaired fear recognition ability. The results show that during fear processing, Met allele carriers show an increased neural response in regions previously implicated in mediating autonomic arousal. Further, the Met carriers show decreased functional connectivity with the hippocampus, which may reflect differential retrieval of emotional associations. Together, these effects show significant differences in the neural substrate for fear processing with genetic variation in BDNF. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

Common breast cancer susceptibility alleles and the risk of breast cancer for BRCA1 and BRCA2 mutation carriers: implications for risk prediction

DEFF Research Database (Denmark)

Antoniou, Antonis C; Beesley, Jonathan; McGuffog, Lesley

2010-01-01

The known breast cancer susceptibility polymorphisms in FGFR2, TNRC9/TOX3, MAP3K1, LSP1, and 2q35 confer increased risks of breast cancer for BRCA1 or BRCA2 mutation carriers. We evaluated the associations of 3 additional single nucleotide polymorphisms (SNPs), rs4973768 in SLC4A7/NEK10, rs650495...

Methionine synthase A2756G and reduced folate carrier1 A80G ...

African Journals Online (AJOL)

Aim of the study: To analyze the effect of methionine synthase (MTR) A2756G, and reduced folate carrier (RFC1) A80G gene polymorphisms on the maternal risk for DS. Patients: This study was conducted in the Medical Genetics Center, Ain-Shams University hospitals, on a total of 170 mothers of children, diagnosed with ...

[Correlation of angiotensin-converting enzyme 2 gene polymorphism with antihypertensive effects of benazepril].

Science.gov (United States)

Chen, Qing; Tang, Xun; Yu, Can-qing; Chen, Da-fang; Tian, Jun; Cao, Yang; Fan, Wen-yi; Cao, Wei-hua; Zhan, Si-yan; Lv, Jun; Guo, Xiao-xia; Li, Li-ming; Hu, Yong-hua

2010-06-18

To explore the correlation of rs2106809 from angiotensin-converting enzyme 2 gene with antihypertensive effects of benazepril, as well as its interactions with polymorphisms of angiotensinogen(AGT) and angiotensin II type 1 receptor(AGTR1) gene. Correlation between rs2106809 and blood pressure reduction was estimated based on a field trail with 1 831 hypertensive patients using benazepril for 2 weeks. Generalized multifactor dimensionality reduction (GMDR) was used to explore the interactions of rs2106809 and 8 single nucleotide polymorphisms (SNPs) of AGTR1 gene and 3 SNPs of AGT gene. rs2106809 was found to be associated with reduction in systolic blood pressure and pulse pressure in women, as well as pulse pressure reduction in men. T allele carriers presented more blood pressure reduction (1.4, 1.3 and 0.9 mmHg/T allele respectively). Gene-gene interactions involving rs2106809 were found in systolic blood pressure reduction of men, and the response to benazepril of non-sensitive genotypes carriers was 8.2 (95% confidence interval: 6.6-9.7) mmHg, lower than that of sensitive genotypes carriers. rs2106809 might act as an independent influencing factor or component of gene-gene interaction in blood pressure reducing effects of benazepril.

Genetic contributions to age-related decline in executive function: a 10-year longitudinal study of COMT and BDNF polymorphisms

Directory of Open Access Journals (Sweden)

Kirk I Erickson

2008-09-01

Full Text Available Genetic variability in the dopaminergic and neurotrophic systems could contribute to age-related impairments in executive control and memory function. In this study we examined whether genetic polymorphisms for catechol-O-methyltransferase (COMT and brain-derived neurotrophic factor (BDNF were related to the trajectory of cognitive decline occurring over a 10-year period in older adults. A single-nucleotide polymorphism (SNP in the COMT (Val158/108Met gene affects the concentration of dopamine in the prefrontal cortex. In addition, a Val/Met substitution in the pro-domain for BDNF (Val66Met affects the regulated secretion and trafficking of BDNF with Met carriers showing reduced secretion and poorer cognitive function. We found that impairments over the 10-year span on a task-switching paradigm did not vary as a function of the COMT polymorphism. However, for the BDNF polymorphism the Met carriers performed worse than Val homozygotes at the first testing session but only the Val homozygotes demonstrated a significant reduction in performance over the 10-year span. Our results argue that the COMT polymorphism does not affect the trajectory of age-related executive control decline, whereas the Val/Val polymorphism for BDNF may promote faster rates of cognitive decay in old age. These results are discussed in relation to the role of BDNF in senescence and the transforming impact of the Met allele on cognitive function in old age.

UGT polymorphisms and lamotrigine clearance during pregnancy

DEFF Research Database (Denmark)

Petrenaite, Vaiva; Öhman, Inger; Ekström, Lena

2018-01-01

OBJECTIVE: To evaluate the impact of maternal UGT1A4 and UGT2B7 genetic polymorphisms and sex of foetus on gestation-induced changes in lamotrigine (LTG) clearance during pregnancy and post-partum (PP). METHODS: Single nucleotide polymorphisms UGT1A4 142T > G, L48V (*3), UGT1A4 70C > A, P24T (*2......), and post-partum (PP) as well as the sex of the foetus. RESULTS: Reductions in the LTG concentration-to-dose ratio (C/D ratio) during pregnancy were seen in all genotype panels and varied between -53% and -74% in T3. Genetic polymorphism of UGT1A4 T142G (*3) and UGT2B7 C802T (*2) had the most pronounced.......015) as well as in T3 compared to the heterozygous carriers (802CT) (p = 0.04). Multiple regression analysis demonstrated that women who carried a female foetus had a significantly higher reductions in the LTG C/D ratio from T0 to the end of pregnancy than those with a male foetus (p = 0...

Effects of BDNF polymorphism and physical activity on episodic memory in the elderly: a cross sectional study.

Science.gov (United States)

Canivet, Anne; Albinet, Cédric T; André, Nathalie; Pylouster, Jean; Rodríguez-Ballesteros, Montserrat; Kitzis, Alain; Audiffren, Michel

2015-01-01

The brain-derived neurotrophic factor (BDNF) concentration is highest in the hippocampus compared with that in other brain structures and affects episodic memory, a cognitive function that is impaired in older adults. According to the neurotrophic hypothesis, BDNF released during physical activity enhances brain plasticity and consequently brain health. However, even if the physical activity level is involved in the secretion of neurotrophin, this protein is also under the control of a specific gene. The aim of the present study was to examine the effect of the interaction between physical activity and BDNF Val66Met (rs6265), a genetic polymorphism, on episodic memory. Two hundred and five volunteers aged 55 and older with a Mini Mental State Examination score ≥ 24 participated in this study. Four groups of participants were established according to their physical activity level and polymorphism BDNF profile (Active Val homozygous, Inactive Val homozygous, Active Met carriers, Inactive Met carriers). Episodic memory was evaluated based on the delayed recall of the Logical Memory test of the MEM III battery. As expected, the physical activity level interacted with BDNF polymorphism to affect episodic memory performance (p physical activity and BDNF Val66Met polymorphism that affects episodic memory in the elderly and confirms that physical activity contributes to the neurotrophic mechanism implicated in cognitive health. The interaction shows that only participants with Val/Val polymorphism benefited from physical activity.

Recklessness as a hallmark of aggressive cancer.

Science.gov (United States)

Noda, Makoto; Takahashi, Chiaki

2007-11-01

Cancer recurrence after surgical treatment is a major concern for patients and doctors. Understanding what makes tumors prone to recurrence would be an important step toward its prevention. Accumulating evidence indicates that the level of membrane-associated protease regulator reversion-inducing cysteine-rich protein with Kazal motifs (RECK) expressed in tumor tissue is a good prognostic indicator in several common cancers. Certain members of the matrix metalloproteinase family are often upregulated in advanced cancers and are known to play important roles in tumor angiogenesis, invasion and metastasis. RECK negatively regulates several matrix metalloproteinases. Therefore, RECK itself may well be considered a promising tool or target molecule to be activated in cancer therapy. Here we review the recent advances in RECK research and discuss some of the important issues to be addressed in future studies.

Polymorphisms of the OXTR Gene to explain why sales professionals love to help customers

NARCIS (Netherlands)

Verbeke, W.; Bagozzi, R.P.; van den Berg, W.E.; Lemmens, A.

2013-01-01

Polymorphisms of the OXTR gene affect people’s social interaction styles in various social encounters: carriers of the OXTR GG, compared to the OXTR AA/AG in general, are more motivated to interact socially and detect social salience. We focus on sales professionals operating in knowledge intensive

Single-tube tetradecaplex panel of highly polymorphic microsatellite markers hemophilia A.

Science.gov (United States)

Zhao, M; Chen, M; Tan, A S C; Cheah, F S H; Mathew, J; Wong, P C; Chong, S S

2017-07-01

Essentials Preimplantation genetic diagnosis (PGD) of severe hemophilia A relies on linkage analysis. Simultaneous multi-marker screening can simplify selection of informative markers in a couple. We developed a single-tube tetradecaplex panel of polymorphic markers for hemophilia A PGD use. Informative markers can be used for linkage analysis alone or combined with mutation detection. Background It is currently not possible to perform single-cell preimplantation genetic diagnosis (PGD) to directly detect the common inversion mutations of the factor VIII (F8) gene responsible for severe hemophilia A (HEMA). As such, PGD for such inversion carriers relies on indirect analysis of linked polymorphic markers. Objectives To simplify linkage-based PGD of HEMA, we aimed to develop a panel of highly polymorphic microsatellite markers located near the F8 gene that could be simultaneously genotyped in a multiplex-PCR reaction. Methods We assessed the polymorphism of various microsatellite markers located ≤ 1 Mb from F8 in 177 female subjects. Highly polymorphic markers were selected for co-amplification with the AMELX/Y indel dimorphism in a single-tube reaction. Results Thirteen microsatellite markers located within 0.6 Mb of F8 were successfully co-amplified with AMELX/Y in a single-tube reaction. Observed heterozygosities of component markers ranged from 0.43 to 0.84, and ∼70-80% of individuals were heterozygous for ≥ 5 markers. The tetradecaplex panel successfully identified fully informative markers in a couple interested in PGD for HEMA because of an intragenic F8 point mutation, with haplotype phasing established through a carrier daughter. In-vitro fertilization (IVF)-PGD involved single-tube co-amplification of fully informative markers with AMELX/Y and the mutation-containing F8 amplicon, followed by microsatellite analysis and amplicon mutation-site minisequencing analysis. Conclusions The single-tube multiplex-PCR format of this highly polymorphic

BDNF Val66Met polymorphism is associated with higher anticipatory cortisol stress response, anxiety, and alcohol consumption in healthy adults.

Science.gov (United States)

Colzato, Lorenza S; Van der Does, A J Willem; Kouwenhoven, Coen; Elzinga, Bernet M; Hommel, Bernhard

2011-11-01

The brain-derived neurotrophic factor (BDNF) is a key protein in maintaining neuronal integrity. The BDNF gene is thought to play an important role in the pathophysiology of mood and anxiety disorders. The aim of this study was to investigate, for the first time in a single study, the association between BDNF Val(66)Met polymorphism, anxiety, alcohol consumption, and cortisol stress response. 98 healthy university students (54 females and 44 males), genotyped for the Val(66)Met polymorphism, participated in a physical-stress procedure (cold pressure test, CPT) after having been informed that they would undergo a painful experience. Indices of anxiety and of stress were collected from repeated measurement of salivary cortisol, blood pressure, and heart rate. BDNF Met carriers, were more anxious during the CPT (pBDNF Val(66)Met polymorphism with HPA axis reactivity to stress was not modulated by gender. These results suggest that Met carriers are particularly sensitive in anticipating stressful events, which extends previous findings on the moderating role of the BDNF Val(66)Met polymorphism in the face of stressful life events. Copyright © 2011 Elsevier Ltd. All rights reserved.

The BDNF Val66Met Polymorphism Influences Reading Ability and Patterns of Neural Activation in Children.

Directory of Open Access Journals (Sweden)

Kaja K Jasińska

Full Text Available Understanding how genes impact the brain's functional activation for learning and cognition during development remains limited. We asked whether a common genetic variant in the BDNF gene (the Val66Met polymorphism modulates neural activation in the young brain during a critical period for the emergence and maturation of the neural circuitry for reading. In animal models, the bdnf variation has been shown to be associated with the structure and function of the developing brain and in humans it has been associated with multiple aspects of cognition, particularly memory, which are relevant for the development of skilled reading. Yet, little is known about the impact of the Val66Met polymorphism on functional brain activation in development, either in animal models or in humans. Here, we examined whether the BDNF Val66Met polymorphism (dbSNP rs6265 is associated with children's (age 6-10 neural activation patterns during a reading task (n = 81 using functional magnetic resonance imaging (fMRI, genotyping, and standardized behavioral assessments of cognitive and reading development. Children homozygous for the Val allele at the SNP rs6265 of the BDNF gene outperformed Met allele carriers on reading comprehension and phonological memory, tasks that have a strong memory component. Consistent with these behavioral findings, Met allele carriers showed greater activation in reading-related brain regions including the fusiform gyrus, the left inferior frontal gyrus and left superior temporal gyrus as well as greater activation in the hippocampus during a word and pseudoword reading task. Increased engagement of memory and spoken language regions for Met allele carriers relative to Val/Val homozygotes during reading suggests that Met carriers have to exert greater effort required to retrieve phonological codes.

The BDNF Val66Met Polymorphism Influences Reading Ability and Patterns of Neural Activation in Children.

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Jasińska, Kaja K; Molfese, Peter J; Kornilov, Sergey A; Mencl, W Einar; Frost, Stephen J; Lee, Maria; Pugh, Kenneth R; Grigorenko, Elena L; Landi, Nicole

2016-01-01

Understanding how genes impact the brain's functional activation for learning and cognition during development remains limited. We asked whether a common genetic variant in the BDNF gene (the Val66Met polymorphism) modulates neural activation in the young brain during a critical period for the emergence and maturation of the neural circuitry for reading. In animal models, the bdnf variation has been shown to be associated with the structure and function of the developing brain and in humans it has been associated with multiple aspects of cognition, particularly memory, which are relevant for the development of skilled reading. Yet, little is known about the impact of the Val66Met polymorphism on functional brain activation in development, either in animal models or in humans. Here, we examined whether the BDNF Val66Met polymorphism (dbSNP rs6265) is associated with children's (age 6-10) neural activation patterns during a reading task (n = 81) using functional magnetic resonance imaging (fMRI), genotyping, and standardized behavioral assessments of cognitive and reading development. Children homozygous for the Val allele at the SNP rs6265 of the BDNF gene outperformed Met allele carriers on reading comprehension and phonological memory, tasks that have a strong memory component. Consistent with these behavioral findings, Met allele carriers showed greater activation in reading-related brain regions including the fusiform gyrus, the left inferior frontal gyrus and left superior temporal gyrus as well as greater activation in the hippocampus during a word and pseudoword reading task. Increased engagement of memory and spoken language regions for Met allele carriers relative to Val/Val homozygotes during reading suggests that Met carriers have to exert greater effort required to retrieve phonological codes.

Hydrocortisone fails to abolish NF-κB1 protein nuclear translocation in deletion allele carriers of the NFKB1 promoter polymorphism (-94ins/delATTG and is associated with increased 30-day mortality in septic shock.

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Simon T Schäfer

Full Text Available BACKGROUND: Previous investigations and meta-analyses on the effect of glucocorticoids on mortality in septic shock revealed mixed results. This heterogeneity might be evoked by genetic variations. Such candidate is a promoter polymorphism (-94ins/delATTG of the gene encoding the ubiquitous transcription-factor nuclear-factor-κB (NF-κB which binds to recognition elements in the promoter of several genes encoding for the innate immune-system. In turn, hydrocortisone inhibits NF-κB nuclear translocation and thus transcription of key immune-response regulators. Accordingly, we tested the hypotheses that hydrocortisone has a NFKB1 genotype dependent effect on 1 NF-κB1 nuclear translocation evoked by lipopolysaccharide (LPS in monocytes in vitro, and 2 mortality in septic shock. METHODS: Monocytes of volunteers with the homozygous insertion (II; n = 5 or deletion (DD; n = 6 NFKB1 genotype were incubated with 10 µgml-1 LPS ± hydrocortisone (10-5M, and NF-κB1 nuclear translocation was assessed (immunofluorescence. Furthermore, we analyzed 30-day-mortality in 160 patients with septic shock stratified for both genotype and hydrocortisone therapy. RESULTS: Hydrocortisone inhibited LPS induced nuclear translocation of NF-κB1 in II (25%±11;p = 0.0001 but not in DD genotypes (51%±15;p = n.s.. Onehundredandfour of 160 patients with septic shock received hydrocortisone, at the discretion of the intensivist. NFKB1 deletion allele carriers (ID/DD receiving hydrocortisone had a much greater 30-day-mortality (57.6% than II genotypes (24.4%; HR:3.18, 95%-CI:1.61-6.28;p = 0.001. In contrast, 30-day mortality was 22.2% in ID/DD and 25.0% in II genotypes without hydrocortisone therapy. Results were similar when using propensity score matching to account for possible bias in the intensivists' decision to administer hydrocortisone. CONCLUSION: Hydrocortisone fails to inhibit LPS induced nuclear NF-κB1 translocation in deletion allele

Hydrocortisone Fails to Abolish NF-κB1 Protein Nuclear Translocation in Deletion Allele Carriers of the NFKB1 Promoter Polymorphism (-94ins/delATTG) and Is Associated with Increased 30-Day Mortality in Septic Shock

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Schäfer, Simon T.; Gessner, Sophia; Scherag, André; Rump, Katharina; Frey, Ulrich H.; Siffert, Winfried; Westendorf, Astrid M.; Steinmann, Jörg; Peters, Jürgen; Adamzik, Michael

2014-01-01

Background Previous investigations and meta-analyses on the effect of glucocorticoids on mortality in septic shock revealed mixed results. This heterogeneity might be evoked by genetic variations. Such candidate is a promoter polymorphism (-94ins/delATTG) of the gene encoding the ubiquitous transcription-factor nuclear-factor-κB (NF-κB) which binds to recognition elements in the promoter of several genes encoding for the innate immune-system. In turn, hydrocortisone inhibits NF-κB nuclear translocation and thus transcription of key immune-response regulators. Accordingly, we tested the hypotheses that hydrocortisone has a NFKB1 genotype dependent effect on 1) NF-κB1 nuclear translocation evoked by lipopolysaccharide (LPS) in monocytes in vitro, and 2) mortality in septic shock. Methods Monocytes of volunteers with the homozygous insertion (II; n = 5) or deletion (DD; n = 6) NFKB1 genotype were incubated with 10 µgml-1 LPS ± hydrocortisone (10-5M), and NF-κB1 nuclear translocation was assessed (immunofluorescence). Furthermore, we analyzed 30-day-mortality in 160 patients with septic shock stratified for both genotype and hydrocortisone therapy. Results Hydrocortisone inhibited LPS induced nuclear translocation of NF-κB1 in II (25%±11;p = 0.0001) but not in DD genotypes (51%±15;p = n.s.). Onehundredandfour of 160 patients with septic shock received hydrocortisone, at the discretion of the intensivist. NFKB1 deletion allele carriers (ID/DD) receiving hydrocortisone had a much greater 30-day-mortality (57.6%) than II genotypes (24.4%; HR:3.18, 95%-CI:1.61-6.28;p = 0.001). In contrast, 30-day mortality was 22.2% in ID/DD and 25.0% in II genotypes without hydrocortisone therapy. Results were similar when using propensity score matching to account for possible bias in the intensivists' decision to administer hydrocortisone. Conclusion Hydrocortisone fails to inhibit LPS induced nuclear NF-κB1 translocation in deletion allele carriers of the

BDNF val66met polymorphism affects aging of multiple types of memory.

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Kennedy, Kristen M; Reese, Elizabeth D; Horn, Marci M; Sizemore, April N; Unni, Asha K; Meerbrey, Michael E; Kalich, Allan G; Rodrigue, Karen M

2015-07-01

The BDNF val66met polymorphism (rs6265) influences activity-dependent secretion of brain-derived neurotrophic factor in the synapse, which is crucial for learning and memory. Individuals homozygous or heterozygous for the met allele have lower BDNF secretion than val homozygotes and may be at risk for reduced declarative memory performance, but it remains unclear which types of declarative memory may be affected and how aging of memory across the lifespan is impacted by the BDNF val66met polymorphism. This cross-sectional study investigated the effects of BDNF polymorphism on multiple indices of memory (item, associative, prospective, subjective complaints) in a lifespan sample of 116 healthy adults aged 20-93 years. Advancing age showed a negative effect on item, associative and prospective memory, but not on subjective memory complaints. For item and prospective memory, there were significant age×BDNF group interactions, indicating the adverse effect of age on memory performance across the lifespan was much stronger in the BDNF met carriers than for the val homozygotes. BDNF met carriers also endorsed significantly greater subjective memory complaints, regardless of age, and showed a trend (pmemory performance compared to val homozygotes. These results suggest that genetic predisposition to the availability of brain-derived neurotrophic factor, by way of the BDNF val66met polymorphism, exerts an influence on multiple indices of episodic memory - in some cases in all individuals regardless of age (subjective memory and perhaps associative memory), in others as an exacerbation of age-related differences in memory across the lifespan (item and prospective memory). This article is part of a Special Issue entitled Memory & Aging. Copyright © 2014 Elsevier B.V. All rights reserved.

Leptin promoter gene polymorphism on -2549 position decreases plasma leptin and increases appetite in normal weight volunteers

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Sandra Bragança Coelho

2014-05-01

Full Text Available Introduction: Investigate whether polymorphism in the promoter region encoding leptin and leptin receptor gene, in normal weight individuals, affects hormonal and appetite responses to peanuts.Materials and methods: Appetite, anthropometric indices, body composition, physical activity, dietary intake and leptin, ghrelin and insulin levels were monitored. Polymorphism analyses were also carried out.Results: None of the treatments led to statistical differences in the analyzed hormones. No polymorphism was found for leptin receptor gene, while for leptin gene, 50% of the volunteers presented one polymorphic allele and 13% presented both polymorphic alleles. These last ones presented lower body fat mass, leptin and ghrelin plasma concentrations, and fullness rates. They also presented higher hunger, desire to eat, and desire to eat sweet and salty foods.Conclusions: Peanut did not affect appetite and presented no different hormonal responses, compared to other foods studied. Polymorphic allele carriers in both alleles presented higher probability to develop obesity. However, the magnitude of this probability could not be measured.

Angiotensin-converting enzyme insertion/deletion polymorphism association with obesity and some related disorders in Egyptian females: a case-control observational study.

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Motawi, Tarek K; Shaker, Olfat G; Shahin, Nancy N; Ahmed, Nancy M

2016-01-01

According to the WHO report in 2015, obesity is the fifth leading cause of death worldwide, and the prevalence of Egyptian female obesity is 37.5 %. Since obesity is highly influenced by genetics, and adipose tissue renin-angiotensin system is over-activated in obesity, the effect of angiotensin-converting enzyme (ACE) insertion/deletion (I/D) polymorphism on obesity and related disorders was studied in several populations, because of its effect on ACE activity. Our objective was to study the association of ACE I/D polymorphism with obesity and certain related disorders, namely hypertension, insulin resistance and metabolic syndrome, in Egyptian females. Eighty female volunteers were recruited, blood pressure and body measurements were recorded and a fasting blood sample was obtained for the quantitation of glucose, lipid profile, insulin, leptin and identification of ACE I/D polymorphs. Subjects were grouped based on hypertension and obesity states. Comparisons of continuous parameters were made with independent sample t -test between two groups. The frequencies of ACE genotypes and alleles, and the association between gene polymorphism and metabolic parameters were assessed using chi-square or Fisher's exact test. Genotype frequencies were in Hardy-Weinberg equilibrium for all groups. Genotype distribution did not differ significantly between controls and cases of all the studied disorders. Although DD carriers had apparently higher parameters of blood pressure, lipid profile and insulin resistance, only diastolic blood pressure was almost significant ( p  = 0.057). I-carriers were significantly less susceptible to hypertension than DD carriers having normal waist/hip ratio ( p  = 0.007, OR = 17.29, CI = 1.81-164.96) and normal conicity index ( p  = 0.024, OR = 7.00, CI = 1.36-35.93). In DD genotype carriers, a significant association was found between insulin resistance and high body mass index ( p  = 0.004, OR = 8.89, CI�

Blood pressure levels in male carriers of Arg82Cys in CD300LG

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Støy, Julie; Grarup, Niels; Hørlyck, Arne

2014-01-01

found to be associated with fasting HDL-cholesterol and triglyceride levels. The polymorphism has not been detected in hypertension GWAS potentially due to its low frequency, but CD300LG has been linked to blood pressure as CD300LG knockout mice have changes in blood pressure. Twenty......-four-hour ambulatory blood pressure was obtained in human CD300LG CT-carriers to follow up on these observations. METHODS: Twenty healthy male CD300LG rs72836561 CT-carriers matched for age and BMI with 20 healthy male CC-carriers. Office blood pressure, 24-hour ambulatory blood pressure, carotid intima......-media thickness (CIMT), and fasting blood samples were evaluated. The clinical study was combined with a genetic-epidemiological study to replicate the association between blood pressure and CD300LG Arg82Cys in 2,637 men and 3,249 women. RESULTS: CT-carriers had a higher 24-hour ambulatory systolic blood pressure...

PARP1 Val762Ala polymorphism reduces enzymatic activity

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Wang Xiaogan; Wang Zhaoqi; Tong Weimin; Shen Yan

2007-01-01

Poly(ADP-ribose) polymerase 1 (PARP1) modifies a variety of nuclear proteins by poly(ADP-ribosyl)ation, and plays diverse roles in molecular and cellular processes. A common PARP1 single nucleotide polymorphism (SNP) at codon 762, resulting in the substitution of alanine (Ala) for valine (Val) in the catalytic domain has been implicated in susceptibility to cancer. To characterize the functional effect of this polymorphism on PARP1, we performed in vitro enzymatic analysis on PARP1-Ala762 and PARP1-Val762. We found that PARP1-Ala762 displayed 57.2% of the activity of PARP1-Val762 for auto-poly(ADP-ribosyl)ation and 61.9% of the activity of PARP1-Val762 for trans-poly(ADP-ribosyl)ation of histone H1. The kinetic characterization revealed that the K m of PARP1-Ala762 was increased to a 1.2-fold of the K m of PARP1-Val762 for trans-poly(ADP-ribosyl)ation. Thus, the PARP1 Val762Ala polymorphism reduces the enzymatic activity of PARP1 by increasing K m . This finding suggests that different levels of poly(ADP-ribosyl)ation by PARP1 might aid in understanding Cancer risk of carriers of the PARP1 Val762Ala polymorphism

Polymorphism of Kynurenine Pathway-Related Genes, Kynurenic Acid, and Psychopathological Symptoms in HIV.

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Douet, Vanessa; Tanizaki, Naomi; Franke, Adrian; Li, Xingnan; Chang, Linda

2016-09-01

HIV-infection is associated with neuroinflammation and greater psychopathological symptoms, which may be mediated by imbalances in the kynurenic pathway (KP). Two key KP enzymes that catabolize kynurenine include kynurenine-aminotransferase II (KATII), which yields antioxidative kynurenine acid [KYNA] in astrocytes, and kynurenine-3-monooxygenase (KMO), which produces neurotoxic metabolites in microglia. The relationships between polymorphisms in KMO and KATII, psychopathological symptoms, and cerebrospinal fluid (CSF) [KYNA] were evaluated in subjects with and without HIV-infection. Seventy-two HIV-positive and 72-seronegative (SN) participants were genotyped for KATII-rs1480544 and KMO-rs1053230. Although our participants were not currently diagnosed with depression or anxiety, they were assessed for psychopathological distress with Center for Epidemiologic Studies-Depression scale and Symptom Checklist-90-Revised. CSF-[KYNA] was also measured in 100 subjects (49 HIV/51 SN). HIV-participants had more psychopathological distress than SN, especially for anxiety. KATII-by-HIV interactions were found on anxiety, interpersonal sensitivity and obsessive compulsivity; KATII-C-carriers had lower scores than TT-carriers in SN but not in HIV. In contrast, the KMO-polymorphism had no influence on psychopathological symptoms in both groups. Overall, CSF-[KYNA] increased with age independently of HIV-serostatus, except KATII-TT-carriers tended to show no age-dependent variations. Therefore, the C-allele in KATII-rs1480544 appears to be protective against psychopathological distress in SN but not in HIV individuals, who had more psychopathological symptoms and likely greater neuroinflammation. The age-dependent increase in CSF-[KYNA] may reflect a compensatory response to age-related inflammation, which may be deficient in KATII-TT-carriers. Targeted treatments that decrease neuroinflammation and increase KYNA in at risk KATII-TT-carriers may reduce psychopathological symptoms

Effects of BDNF polymorphisms on antidepressant action.

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Tsai, Shih-Jen; Hong, Chen-Jee; Liou, Ying-Jay

2010-12-01

Evidence suggests that the down-regulation of the signaling pathway involving brain-derived neurotrophic factor (BDNF), a molecular element known to regulate neuronal plasticity and survival, plays an important role in the pathogenesis of major depression. The restoration of BDNF activity induced by antidepressant treatment has been implicated in the antidepressant therapeutic mechanism. Because there is variability among patients with major depressive disorder in terms of response to antidepressant treatment and since genetic factors may contribute to this inter-individual variability in antidepressant response, pharmacogenetic studies have tested the associations between genetic polymorphisms in candidate genes related to antidepressant therapeutic action. In human BDNF gene, there is a common functional polymorphism (Val66Met) in the pro-region of BDNF, which affects the intracellular trafficking of proBDNF. Because of the potentially important role of BDNF in the antidepressant mechanism, many pharmacogenetic studies have tested the association between this polymorphism and the antidepressant therapeutic response, but they have produced inconsistent results. A recent meta-analysis of eight studies, which included data from 1,115 subjects, suggested that the Val/Met carriers have increased antidepressant response in comparison to Val/Val homozygotes, particularly in the Asian population. The positive molecular heterosis effect (subjects heterozygous for a specific genetic polymorphism show a significantly greater effect) is compatible with animal studies showing that, although BDNF exerts an antidepressant effect, too much BDNF may have a detrimental effect on mood. Several recommendations are proposed for future antidepressant pharmacogenetic studies of BDNF, including the consideration of multiple polymorphisms and a haplotype approach, gene-gene interaction, a single antidepressant regimen, controlling for age and gender interactions, and pharmacogenetic

The ACE Gene Insertion/Deletion Polymorphism and Cerebrovascular Diseases in Uzbek Patients with Arterial Hypertension

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Nargiza U. Makhkamova

2016-09-01

Full Text Available The aim of the present study was to investigate the association between the ACE gene I/D polymorphism and the development of hypertensive encephalopathy (HE in Uzbek patients with hypertension (HT. Materials and methods: The study included 91 male patients aged from 32 to 74 years (mean age 52.5±9.2 with HT Grade 1, 2 and 3 (ESH/ESC, 2013 [4] and presence of HE. All patients were checked on office BP using Korotkov’s method and ambulatory blood pressure monitoring (ABPM. Intima-media thickness (IMT of the carotid artery was measured by a 7.5MHz high-resolution ultrasound. Genomic DNA was isolated from peripheral blood using the DiatomTM DNA Prep 200 Kit according to the manufacturer's protocol. ACE gene I/D polymorphism genotypes were determined by PCR. Results: Among HT patients with HE, we have identified a statistically significant predominance of ID genotype carriers (65.9% against carriers of the II genotype (18.75 and DD genotype (15.4% (P=0.000; the frequency of I and D alleles was 51.6% and 48.4%, respectively (P>0.05. Comparative analysis showed a possible association between the ID genotype/D allele and HE development in HT patients, according to the general model (OR = 6.36; 95% CI 3.04 -13.31; p=0.000 and multiplicative model (OR = 2.02; 95% CI 1.25 -3.27; p=0.004 of inheritance. High grades of HT were predominant in carriers of the DD genotype. IMT was significantly higher in carriers of the DD genotype than in carriers of the II and ID genotypes. The carriage of D allele was associated with the highest levels of TC, TG, and VLDL-C. Carriers of the DD genotype were characterized by higher values of daytime SBP, nighttime SBP variability and nighttime SBP load.

A case of hypocholesterolemia and steatosis in a carrier of a PCSK9 loss-of-function mutation and polymorphisms predisposing to nonalcoholic fatty liver disease.

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Di Filippo, Mathilde; Vokaer, Benoit; Seidah, Nabil G

We report a new case of hypobetalipoproteinemia in a 44-year-old man of Peruvian origin exhibiting a heterozygous PCSK9 missense mutation (c.946 G>T, p. Gly316Cys). In vitro functional studies demonstrated that this mutation leads to a loss of function of PCSK9 on low-density lipoprotein receptor degradation. This patient exhibited liver steatosis; he was neither diabetic, nor obese or alcoholic, but is a carrier of 2 polymorphisms, p.Ile148Met (rs738409) and p.Glu167Lys (rs58542926) on PNPLA3 and TM6SF2 gene, respectively, previously shown to be associated with nonalcoholic steatosis and fibrosis evolution. These data suggested that if a resistance to hepatic steatosis mediated by the PCSK9 deficiency exists, as demonstrated in mice, it is not sufficient to prevent hepatic fatty accumulation in the case of genetic factors predisposing to nonalcoholic fatty liver disease. Copyright © 2017 National Lipid Association. Published by Elsevier Inc. All rights reserved.

The effects of gender and COMT Val158Met polymorphism on fearful facial affect recognition: a fMRI study.

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Kempton, Matthew J; Haldane, Morgan; Jogia, Jigar; Christodoulou, Tessa; Powell, John; Collier, David; Williams, Steven C R; Frangou, Sophia

2009-04-01

The functional catechol-O-methyltransferase (COMT Val108/158Met) polymorphism has been shown to have an impact on tasks of executive function, memory and attention and recently, tasks with an affective component. As oestrogen reduces COMT activity, we focused on the interaction between gender and COMT genotype on brain activations during an affective processing task. We used functional MRI (fMRI) to record brain activations from 74 healthy subjects who engaged in a facial affect recognition task; subjects viewed and identified fearful compared to neutral faces. There was no main effect of the COMT polymorphism, gender or genotypexgender interaction on task performance. We found a significant effect of gender on brain activations in the left amygdala and right temporal pole, where females demonstrated increased activations over males. Within these regions, Val/Val carriers showed greater signal magnitude compared to Met/Met carriers, particularly in females. The COMT Val108/158Met polymorphism impacts on gender-related patterns of activation in limbic and paralimbic regions but the functional significance of any oestrogen-related COMT inhibition appears modest.

Alpha-1 antitrypsin gene polymorphism in Chronic Obstructive Pulmonary Disease (COPD

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Sabri Denden

2010-01-01

Full Text Available Alpha-1-antitrypsin (AAT plays an important role in the pathogenesis of emphysema, the pathological lesion underlying the majority of the manifestations of Chronic Obstructive Pulmonary Disease (COPD. In this study we tested the hypothesis that common AAT polymorphisms influence the risk of developing COPDs. We investigated PiM1 (Ala213Val, PiM2 (Arg101His, PiM3 (Glu376Asp, PiS (Glu264Val and PiZ (Glu342Lys SERPINA1 alleles in 100 COPD patients and 200 healthy controls. No significant differences were observed in allele frequencies between COPD patients and controls, neither did haplotype analysis show significant differences between the two groups. A cross-sectional study revealed no significant relationship between common SERPINA1 polymorphisms (PiM1, PiM2, PiM3 and the emphysematous type of COPD. In addition, FEV1 annual decline, determined during a two-year follow up period, revealed no difference among carriers of the tested polymorphisms.

Preprohypocretin polymorphisms in Parkinson disease patients reporting "sleep attacks".

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Rissling, Ida; Körner, Yvonne; Geller, Frank; Stiasny-Kolster, Karin; Oertel, Wolfgang H; Möller, J Carsten

2005-07-01

Previously, we found a significant association between the dopamine D2 receptor gene polymorphism Taq IA and sudden onset of sleep in patients with Parkinson disease. Here we evaluated the association between the preprohypocretin (-909T/C), (-22C/T), and (-20C/A) polymorphisms and sudden onset of sleep in the same population of patients with Parkinson disease. We conducted an association study analyzing the distribution of preprohypocretin polymorphisms in Germanic, caucasian Parkinson disease patients with and without sudden onset of sleep, matched according to drug therapy, disease duration, sex, and age. Movement disorders section at a university hospital. 132 Parkinson disease patients with sudden onset of sleep and 132 Parkinson disease patients without sudden onset of sleep. Blood samples were taken from each participant and used for DNA extraction. Polymorphisms were analyzed by established polymerase chain reaction protocols or direct sequencing. The variant allele T of the (-909T/C) preprohypocretin polymorphism was more commonly found in Parkinson disease patients with sudden onset of sleep. Statistical analysis showed that there were significant differences in the genotype (P = .024) and allele (P = .018) distribution between both groups. For heterozygous and homozygous carriers of allele T, the genotype relative-risk estimates for the presence of sudden onset of sleep were 2.01 (95% confidence interval: 0.76-5.34) and 2.81 (95% confidence interval: 1.09-7.25), respectively. Our results show a significant association between the (-909T/C) preprohypocretin polymorphism and sudden onset of sleep in Parkinson disease. However, we could not demonstrate any interaction between the Taq IA and (-909T/C) polymorphisms with respect to the occurrence of sudden onset of sleep, suggesting that multiple genetic factors may contribute to the pathogenesis of this phenomenon.

Age-related olfactory decline is associated with the BDNF val66met polymorphism: evidence from a population-based study

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Margareta Hedner

2010-06-01

Full Text Available The present study investigates the effect of the brain-derived neurotrophic factor (BDNF val66met polymorphism on change in olfactory function in a large scale, longitudinal population-based sample (n=836. The subjects were tested on a 13 item force-choice odor identification test on two test occasions over a 5-year-interval. Sex, education, health-related factors, and semantic ability were controlled for in the statistical analyses. Results showed an interaction effect of age and BDNF val66met on olfactory change, such that the magnitude of olfactory decline in the older age cohort (70-90 years old at baseline was larger for the val homozygote carriers than for the met carriers. The older met carriers did not display larger age-related decline in olfactory function compared to the younger group. The BDNF val66met polymorphism did not affect the rate of decline in the younger age cohort (45-65 years. The findings are discussed in the light of the proposed roles of BDNF in neural development and maintenance.

COMT Val158Met polymorphism influences the susceptibility to framing in decision-making: OFC-amygdala functional connectivity as a mediator.

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Gao, Xiaoxue; Gong, Pingyuan; Liu, Jinting; Hu, Jie; Li, Yue; Yu, Hongbo; Gong, Xiaoliang; Xiang, Yang; Jiang, Changjun; Zhou, Xiaolin

2016-05-01

Individuals tend to avoid risk in a gain frame, in which options are presented in a positive way, but seek risk in a loss frame, in which the same options are presented negatively. Previous studies suggest that emotional responses play a critical role in this "framing effect." Given that the Met allele of COMT Val158Met polymorphism (rs4680) is associated with the negativity bias during emotional processing, this study investigated whether this polymorphism is associated with individual susceptibility to framing and which brain areas mediate this gene-behavior association. Participants were genotyped, scanned in resting state, and completed a monetary gambling task with options (sure vs risky) presented as potential gains or losses. The Met allele carriers showed a greater framing effect than the Val/Val homozygotes as the former gambled more than the latter in the loss frame. Moreover, the gene-behavior association was mediated by resting-state functional connectivity (RSFC) between orbitofrontal cortex (OFC) and bilateral amygdala. Met allele carriers showed decreased RSFC, thereby demonstrating higher susceptibility to framing than Val allele carriers. These findings demonstrate the involvement of COMT Val158Met polymorphism in the framing effect in decision-making and suggest RSFC between OFC and amygdala as a neural mediator underlying this gene-behavior association. Hum Brain Mapp 37:1880-1892, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Interleukin-6 and interleukin-10 gene polymorphisms and the risk of further periodontal disease progression.

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Chatzopoulos, Georgios; Doufexi, Aikaterini-Ellisavet; Wolff, Larry; Kouvatsi, Anastasia

2018-03-08

Susceptible genotypes to periodontal disease are associated with disease onset and progression. The aim of this study was to examine the effect of gene polymorphisms on the risk of further disease progression and the need for further treatment among adults with chronic periodontal disease. Sixty-seven patients diagnosed with chronic periodontitis were grouped according to genotype status and risk of further progression of disease and tooth loss. All individuals were clinically evaluated for probing pocket depth, clinical attachment loss and bleeding on probing at baseline and 45 days after treatment. Blood samples were collected at baseline and genotyping of the polymorphisms in IL-6 (rs1800796) and IL-10 (rs1800872) genes were performed by PCR. Following DNA separation and genotyping, 65.7% of the patients were homozygous carriers of the IL-6 -572G and 49.3% were carriers of the IL-10 -592A allele. Individuals at risk of disease progression ranged from 7.5% to 62.7% based on the criteria used. Carriers of the IL-10 -592A allele were significantly associated with BOP ≥ 30% and therefore exhibited a higher risk of further periodontal breakdown (p = 0.018) with an odds ratio of 1.18. None of the other definitions of disease progression were significantly associated with the examined IL-6 and IL-10 genotypes (p > 0.05). IL-10 polymorphism was associated with an increased risk of further disease progression and the potential need for further treatment following non-surgical periodontal treatment. Susceptible IL-6 genotypes were not associated with the risk of persisting or recurrent disease activity.

Depressive symptoms in schizophrenia and dopamine and serotonin gene polymorphisms.

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Peitl, Vjekoslav; Štefanović, Mario; Karlović, Dalibor

2017-07-03

Although depressive symptoms seem to be frequent in schizophrenia they have received significantly less attention than other symptom domains. As impaired serotonergic and dopaminergic neurotransmission is implicated in the pathogenesis of depression and schizophrenia this study sought to investigate the putative association between several functional gene polymorphisms (SERT 5-HTTLPR, MAO-A VNTR, COMT Val158Met and DAT VNTR) and schizophrenia. Other objectives of this study were to closely examine schizophrenia symptom domains by performing factor analysis of the two most used instruments in this setting (Positive and negative syndrome scale - PANSS and Calgary depression rating scale - CDSS) and to examine the influence of investigated gene polymorphisms on the schizophrenia symptom domains, focusing on depressive scores. A total of 591 participants were included in the study (300 schizophrenic patients and 291 healthy volunteers). 192 (64%) of schizophrenic patients had significant depressive symptoms. Genotype distribution revealed no significant differences regarding all investigated polymorphisms except the separate gender analysis for MAO-A gene polymorphism which revealed significantly more allele 3 carriers in schizophrenic males. Factor analysis of the PANSS scale revealed the existence of five separate factors (symptom domains), while the CDSS scale revealed two distinct factors. Several investigated gene polymorphisms (mostly SERT and MAO-A, but also COMT) significantly influenced two factors from the PANSS (aggressive/impulsive and negative symptoms) and one from the CDSS scale (suicidality), respectively. Depressive symptoms in schizophrenic patients may be influenced by functional gene polymorphisms, especially those implicated in serotonergic neurotransmission. Copyright © 2017 Elsevier Inc. All rights reserved.

Frequency of distribution of leptin receptor gene polymorphism in obstructive sleep apnea patients.

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Popko, K; Gorska, E; Wasik, M; Stoklosa, A; Pływaczewski, R; Winiarska, M; Gorecka, D; Sliwinski, P; Demkow, U

2007-11-01

Leptin is an adipocyte-derived hormone regulating energy homeostasis and body weight. Leptin concentration is increased in patients with the obstructive sleep apnea syndrome (OSAS). Leptin receptor (LEPR) is a single transmembrane protein belonging to the superfamily of cytokine receptors related by a structure to the hemopoietin receptor family. The aim of the present study was to evaluate the frequency of distribution of leptin receptor gene polymorphism GLN223ARG in OSAS patients compared with healthy controls. The examined group included 179 subjects: 102 OSAS patients (74 men and 28 women) and 77 non-apneic controls (39 men and 38 women). Genomic DNA was isolated with the use of a column method and genotyping of DNA sequence variation was carried out by restriction enzyme analysis of PCR-amplified DNA. The results revealed a significant correlation between the polymorphism of LEPR and OSAS. Carriers of Arg allele in homozygotic genotype Arg/Arg and heterozygotic genotype Gln/Arg were more often obese and developed OSAS than the group of carriers of homozygotic Gln/Gln genotype. This tendency was observed in the whole examined population and in the group of obese women. We also found the highest levels of total cholesterol, LDL, HDL, and triglycerides in the group of homozygotic Arg/Arg genotype carriers, lower in heterozygotic Gln/Arg genotype carriers, and the lowest in the group of persons carring homozygotic Gln/Gln genotype. The presence of Arg allel seems linked to a higher risk of obesity and higher lipid levels in OSAS patients. OSAS may have a strong genetic basis due to the effects from a variety of genes including those for leptin receptor.

[Association of I/D and -786 Polymorphisms of ACE and NOS3 Genes With Features of the Course of Ischemic Heart Disease and Diabetes Mellitus Type 2].

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Afanasiev, S A; Muslimova, E F; Rebrov, T Y; Sergienko, T N; Repin, A N

2016-09-01

to study relationship of ACE insertion-deletion (I/D) polymorphism and NOS3 T-786C polymorphism with characteristics of the course of ischemic heart disease (IHD) at the background of diabetes mellitus. Were examined 114 patients with IHD, 29.8% of patients had type 2 diabetes mellitus. ACE and NOS3 polymorphisms were determined by allele-specific polymerase chain reaction with primers by "Lytech". Patients with combined pathology belonged to older age group, had increased frequency of obesity and predominance of functional class II chronic heart failure. In this group we detected association of D allele of the ACE gene with higher frequency of dyslipidemia and obesity. Among patients with IHD without diabetes we observed associations of ACE I/D and NOS3 T-786C polymorphisms (close and moderate, respectively) with severity of effort angina. We also found that frequency of dyslipidemia among carriers of II and TT genotypes was lower than among carriers of other genotypes. Presence of type 2 diabetes as background pathology leads to a change of character of association of ACE I/D and NOS3 T-786C polymorphisms with clinical characteristics of patients with IHD.

Arsenic methylation capacity in relation to nutrient intake and genetic polymorphisms in one-carbon metabolism.

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Gamboa-Loira, Brenda; Hernández-Alcaraz, César; Gandolfi, A Jay; Cebrián, Mariano E; Burguete-García, Ana; García-Martínez, Angélica; López-Carrillo, Lizbeth

2018-07-01

Nutrients and genetic polymorphisms participating in one-carbon metabolism may explain interindividual differences in inorganic arsenic (iAs) methylation capacity, which in turn may account for variations in susceptibility to iAs-induced diseases. 1) To evaluate the association between polymorphisms in five one-carbon metabolism genes (FOLH1 c.223 T > C, MTHFD1 c.1958 G > A, MTHFR c.665 C > T, MTR c.2756 A > G, and MTRR c.66 A > G) and iAs methylation capacity; 2) To assess if previously reported associations between nutrient intake and iAs methylation capacity are modified by those polymorphisms. Women (n = 1027) exposed to iAs in Northern Mexico were interviewed. Blood and urine samples were collected. Nutrient dietary intake was estimated using a validated food frequency questionnaire. iAs methylation capacity was calculated from urinary iAs species (iAs, monomethylarsonic acid [MMA] and dimethylarsinic acid [DMA]) measured by high performance liquid chromatography (HPLC-ICP-MS). One polymorphism in each of the five genes evaluated was genotyped by allelic discrimination. Multivariable linear regression models were used to evaluate if genetic polymorphisms modified the associations between iAs methylation capacity parameters and nutrient intake. The median (min-max) concentration of total arsenic (TAs) was 20.2 (1.3-2776.0) µg/g creatinine in the study population. Significant interactions for iAs metabolism were only found with FOLH1 c.223 T > C polymorphism and vitamin B12 intake, so that CT and CC genotype carriers had significantly lower %iAs, and higher DMA/iAs with an increased vitamin B12 intake, as compared to carriers of wild-type TT. Differences in dietary nutrient intake and genetic variants in one-carbon metabolism may jointly influence iAs methylation capacity. Confirmation of these interactions in other populations is warranted. Copyright © 2018 Elsevier Inc. All rights reserved.

The serotonin transporter gene polymorphism 5-HTTLPR moderates the effects of stress on attention-deficit/hyperactivity disorder

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van der Meer, Dennis; Hartman, Catharina A.; Richards, Jennifer; Bralten, Janita B.; Franke, Barbara; Oosterlaan, Jaap; Heslenfeld, Dirk J.; Faraone, Stephen V.; Buitelaar, Jan K.; Hoekstra, Pieter J.

2014-01-01

IntroductionThe role of the serotonin transporter gene polymorphism 5-HTTLPR in attention-deficit/hyperactivity disorder (ADHD) is unclear. Heterogeneity of findings may be explained by gene-environment interactions (GxE), as it has been suggested that S-allele carriers are more reactive to

The serotonin transporter gene polymorphism 5-HTTLPR moderates the effects of stress on attention-deficit/hyperactivity disorder

NARCIS (Netherlands)

Meer, D. van der; Hartman, C.A.; Richards, J.; Bralten, J.B.; Franke, B.; Oosterlaan, J.; Heslenfeld, D.J.; Faraone, S.V.; Buitelaar, J.K.; Hoekstra, P.J.

2014-01-01

INTRODUCTION: The role of the serotonin transporter gene polymorphism 5-HTTLPR in attention-deficit/hyperactivity disorder (ADHD) is unclear. Heterogeneity of findings may be explained by gene-environment interactions (GxE), as it has been suggested that S-allele carriers are more reactive to

The serotonin transporter gene polymorphism 5-HTTLPR moderates the effects of stress on attention-deficit/hyperactivity disorder

NARCIS (Netherlands)

van der Meer, D.; Hartman, C.A.; Richards, J.; Bralten, J.; Franke, B.; Oosterlaan, J.; Heslenfeld, D.J.

2015-01-01

Introduction The role of the serotonin transporter gene polymorphism 5-HTTLPR in attention-deficit/hyperactivity disorder (ADHD) is unclear. Heterogeneity of findings may be explained by gene-environment interactions (GxE), as it has been suggested that S-allele carriers are more reactive to

The serotonin transporter gene polymorphism 5-HTTLPR moderates the effects of stress on attention-deficit/hyperactivity disorder

NARCIS (Netherlands)

van der Meer, D.; Hartman, C.A.; Richards, J.; Bralten, J.; Franke, B.; Oosterlaan, J.; Heslenfeld, D.J.; Faraone, S.V.; Buitelaar, J.K.; Hoekstra, P.J.

2014-01-01

Introduction The role of the serotonin transporter gene polymorphism 5-HTTLPR in attention-deficit/hyperactivity disorder (ADHD) is unclear. Heterogeneity of findings may be explained by gene-environment interactions (GxE), as it has been suggested that S-allele carriers are more reactive to

VEGF Gene Polymorphisms are Associated with Risk of Tetralogy of Fallot

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Li, Xiang; Liu, Chao-Liang; Li, Xiao-Xia; Li, Qing-Chen; Ma, Li-Ming; Liu, Gao-Li

2015-01-01

Background The aim of this study was to investigate associations of 3 common polymorphisms in the VEGF gene, −2578C>A, −634C>G, and 936C>T, with risk of tetralogy of Fallot (TOF) in Chinese Han children. Material/Methods From January 2010 to June 2013, a total of 400 pediatric subjects were recruited, including 160 cases with TOF (TOF group) and 240 healthy controls (control group). The genotypes of 3 common VEGF polymorphisms, −2578C>A, −634C>G, and 936C>T, were analyzed by polymerase chain reaction restriction fragment length polymorphism. All data were analyzed with SPSS 18.0 software. Results No significant differences were observed in body mass index or sex between TOF patients and controls (both P>0.05), but significant differences in age and family history of TOF were observed between the 2 groups (both PA of VEGF was correlated with a significantly increased risk of TOF, and TOF risk in A allele carrier was 1.54-fold higher than that of C allele carrier (OR=1.54, 95%CI=1.14–2.09, P=0.005); the statistical significance was still present after Bonferroni correction (Pc=0.045). GG genotype in −634C>G of VEGF gene was also associated with an increased risk of TOF, and TOF risk in patients with G allele was 1.62-fold higher compared to patients with C allele (OR=1.62, 95%CI=1.19–2.21, P=0.002); the statistical significance was still present after Bonferroni correction (Pc=0.018). Interestingly, T allele in VEGF 936C>T polymorphism is associated with a decreased TOF risk (OR=0.65, 95%CI=0.49–0.87, P=0.003, the statistical significance was still present after Bonferroni correction (Pc=0.027). The result of logistic regression analysis revealed that −2578C>A, −634C>G, and 936C>T genotypes are independently related to the prevalence of TOF (all PA and −634C>G, may be associated with an increased TOF risk, while 936C>T polymorphism may be associated with decreased TOF risk. PMID:26558525

Immuno-related polymorphisms and cervical cancer risk: The IARC multicentric case-control study.

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James McKay

Full Text Available A small proportion of women who are exposed to infection with human-papillomavirus (HPV develop cervical cancer (CC. Genetic factors may affect the risk of progression from HPV infection to cervical precancer and cancer. We used samples from the International Agency for Research on Cancer (IARC multicentric case-control study to evaluate the association of selected genetic variants with CC. Overall, 790 CC cases and 717 controls from Algeria, Morocco, India and Thailand were included. Cervical exfoliated cells were obtained from control women and cervical exfoliated cells or biopsy specimens from cases. HPV-positivity was determined using a general primer GP5+/6+ mediated PCR. Unconditional logistic regression was used to estimate odds ratios (OR and corresponding 95% confidence intervals (CI of host genotypes with CC risk, using the homozygous wild type genotype as the referent category and adjusting by age and study centre. The association of polymorphisms with the risk of high-risk HPV-positivity among controls was also evaluated. A statistically significant association was observed between single nucleotide polymorphism (SNP CHR6 rs2844511 and CC risk: the OR for carriers of the GA or GG genotypes was 0.70 (95% CI: 0.43-1.14 and 0.61 (95% CI: 0.38-0.98, respectively, relative to carriers of AA genotype (p-value for trend 0.03. We also observed associations of borderline significance with the TIPARP rs2665390 polymorphism, which was previously found to be associated with ovarian and breast cancer, and with the EXOC1 rs13117307 polymorphism, which has been linked to cervical cancer in a large study in a Chinese population. We confirmed the association between CC and the rs2844511 polymorphism previously identified in a GWAS study in a Swedish population. The major histocompatibility region of chromosome 6, or perhaps other SNPs in linkage disequilibrium, may be involved in CC onset.

Association of MicroRNA-146a rs2910164 Gene Polymorphism with Metabolic Syndrome.

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Mehanna, E T; Ghattas, M H; Mesbah, N M; Saleh, S M; Abo-Elmatty, D M

2015-01-01

Alteration in microRNA-146a (miRNA-146a) expression is an important event in the pathogenesis of many human diseases. MiRNA-146a rs2910164 is a functional polymorphism that showed association with several diseases. Metabolic syndrome is an aggregation of multiple risk factors including impaired glucose tolerance, increased highdensity lipoprotein, abdominal obesity, and high blood pressure. The aim of this study was to assess the relation of miRNA-146a rs2910164 with metabolic syndrome and its component traits in Egyptian women from the Suez Canal area. The study included 100 healthy female subjects and 100 metabolic syndrome patients. The component traits of metabolic syndrome were determined and the genotypes of the polymorphisms were assessed using the polymerase chain reaction-restriction fragment length polymorphism technique using the restriction enzyme Hpy188I. The rare C allele had a significantly higher frequency in metabolic syndrome patients (P = 0.013). The heterozygote GC and the rare CC genotypes showed a significant increase in body mass index, waist circumference, triglycerides, total cholesterol, low-density lipoprotein, systolic and diastolic blood pressure. The GC genotype was associated with higher fasting blood glucose, fasting serum insulin and insulin resistance. The carriers of CC genotype had significantly lower HDL compared with the GG genotype carriers. In conclusion, The C allele of miRNA-146a rs2910164 showed positive association with increased susceptibility to metabolic syndrome and its phenotypes in the study population.

The Vitamin D Receptor (VDR Gene Polymorphisms in Turkish Brain Cancer Patients

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Bahar Toptaş

2013-01-01

Full Text Available Objective. It has been stated that brain cancers are an increasingly serious issue in many parts of the world. The aim of our study was to determine a possible relationship between Vitamin D receptor (VDR gene polymorphisms and the risk of glioma and meningioma. Methods. We investigated the VDR Taq-I and VDR Fok-I gene polymorphisms in 100 brain cancer patients (including 44 meningioma cases and 56 glioma cases and 122 age-matched healthy control subjects. This study was performed by polymerase chain reaction-based restriction fragment length polymorphism (RF LP. Results. VDR Fok-I ff genotype was significantly increased in meningioma patients (15.9% compared with controls (2.5%, and carriers of Fok-I ff genotype had a 6.47-fold increased risk for meningioma cases. There was no significant difference between patients and controls for VDR Taq-I genotypes and alleles. Conclusions. We suggest that VDR Fok-I genotypes might affect the development of meningioma.

RAGE polymorphisms and oxidative stress levels in Hashimoto's thyroiditis.

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Giannakou, Maria; Saltiki, Katerina; Mantzou, Emily; Loukari, Eleni; Philippou, Georgios; Terzidis, Konstantinos; Lili, Kiriaki; Stavrianos, Charalampos; Kyprianou, Miltiades; Alevizaki, Maria

2017-05-01

Polymorphisms of the receptor for advanced glycation end products (RAGE) gene have been studied in various autoimmune disorders, but not in Hashimoto's thyroiditis. Also, increased oxidative stress has been described in patients with Hashimoto's thyroiditis. The aim of this study was to investigate the possible role of two common RAGE polymorphisms (-429T>C, -374T>A) in Hashimoto's thyroiditis; in parallel, we studied oxidative stress levels. A total of 300 consecutive euthyroid women were examined and classified into three groups: Hashimoto's thyroiditis with treatment (n = 96), Hashimoto's thyroiditis without treatment (n = 109) and controls (n = 95). For a rough evaluation of oxidative stress, total lipid peroxide levels in serum were measured. The -429T>C AluI and -374T>A MfeI polymorphisms of RAGE were studied in genomic DNA. Significant association of the RAGE system with Hashimoto's thyroiditis was found only with regard to the prevalence of the -429T>C, but not with -374T>A polymorphism. The levels of oxidative stress were significantly elevated in Hashimoto's thyroiditis patients under treatment. Further analysis demonstrated that an oxidative stress cut-off value of 590 μmol/L is associated with an increased risk of progression of Hashimoto's thyroiditis from euthyroidism to hypothyroidism; this risk is further increased in carriers of the RAGE -429T>C polymorphism. Our findings indicate that both examined risk factors may be implicated in the occurrence of Hashimoto's thyroiditis, but this covers only a fraction of the pathophysiology of the disease. © 2017 Stichting European Society for Clinical Investigation Journal Foundation.

Role of vitamin D receptor (VDR gene polymorphism in the pathogenesis of juvenile idiopathic arthritis: Theoretical and practical aspects

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M. M. Kostik

2014-01-01

Full Text Available Juvenile idiopathic arthritis (JIA is a chronic inflammatory joint disease associated with impaired immune system performance. The specific features of JIA may be genetically determined.Objective: to assess JIA activity in children with vitamin D receptor (VDR gene ApaI and BsmI polymorphism genotypes.Subjects and methods. The investigation enrolled 71 patients with JIA. When included in the investigation, all the patients were in an active state of disease. JIA activity was assessed using the most commonly used clinical and laboratory indicators, including the Ritchie articular index (RAI, JADAS10, JADAS27, JADAS71, CDAI, DAS, and DAS28. Molecular genetic studies determined VDR gene ApaI and BsmI polymorphisms by polymerase chain reaction, followed by restriction analysis.Results. The boys who were carriers of a bb BsmI polymorphic marker in the VDR gene had a significantly higher activity of JIA measured by RAI (p=0.03, DAS (p<0.05, JADAS10 (p=0.04, JADAS27 (p=0.04, and JADAS71 (p=0.04 than those who were carriers of B allele (BB + Bb genotypes.Conclusion. The carriage of the VDR gene bb BsmI genotype of the polymorphic marker is associated with high JIA activity, which may be regarded as a marker of poor prognosis in boys with JIA.

Infectious mononucleosis-linked HLA class I single nucleotide polymorphism is associated with multiple sclerosis.

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Jafari, Naghmeh; Broer, Linda; Hoppenbrouwers, Ilse A; van Duijn, Cornelia M; Hintzen, Rogier Q

2010-11-01

Multiple sclerosis is a presumed autoimmune disease associated with genetic and environmental risk factors such as infectious mononucleosis. Recent research has shown infectious mononucleosis to be associated with a specific HLA class I polymorphism. Our aim was to test if the infectious mononucleosis-linked HLA class I single nucleotide polymorphism (rs6457110) is also associated with multiple sclerosis. Genotyping of the HLA-A single nucleotide polymorphism rs6457110 using TaqMan was performed in 591 multiple sclerosis cases and 600 controls. The association of multiple sclerosis with the HLA-A single nucleotide polymorphism was tested using logistic regression adjusted for age, sex and HLA-DRB1*1501. HLA-A minor allele (A) is associated with multiple sclerosis (OR = 0.68; p = 4.08 × 10( -5)). After stratification for HLA-DRB1*1501 risk allele (T) carrier we showed a significant OR of 0.70 (p = 0.003) for HLA-A. HLA class I single nucleotide polymorphism rs6457110 is associated with infectious mononucleosis and multiple sclerosis, independent of the major class II allele, supporting the hypothesis that shared genetics may contribute to the association between infectious mononucleosis and multiple sclerosis.

The Ala54Thr Polymorphism of the Fatty Acid Binding Protein 2 Gene Modulates HDL Cholesterol in Mexican-Americans with Type 2 Diabetes

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Lorena M. Salto

2015-12-01

Full Text Available The alanine to threonine amino acid substitution at codon 54 (Ala54Thr of the intestinal fatty acid binding protein (FABP2 has been associated with elevated levels of insulin and blood glucose as well as with dyslipidemia. The aim of this study was to characterize the effect of this FABP2 polymorphism in Mexican-Americans with type 2 diabetes (T2D in the context of a three-month intervention to determine if the polymorphism differentially modulates selected clinical outcomes. For this study, we genotyped 43 participant samples and performed post-hoc outcome analysis of the profile changes in fasting blood glucose, HbA1c, insulin, lipid panel and body composition, stratified by the Ala54Thr polymorphism. Our results show that the Thr54 allele carriers (those who were heterozygous or homozygous for the threonine-encoding allele had lower HDL cholesterol and higher triglyceride levels at baseline compared to the Ala54 homozygotes (those who were homozygous for the alanine-encoding allele. Both groups made clinically important improvements in lipid profiles and glycemic control as a response to the intervention. Whereas the Ala54 homozygotes decreased HDL cholesterol in the context of an overall total cholesterol decrease, Thr54 allele carriers increased HDL cholesterol as part of an overall total cholesterol decrease. We conclude that the Ala54Thr polymorphism of FABP2 modulates HDL cholesterol in Mexican-Americans with T2D and that Thr54 allele carriers may be responsive in interventions that include dietary changes.

PPARγ gene polymorphism, C-reactive protein level, BMI and periodontitis in post-menopausal Japanese women.

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Wang, Yangming; Sugita, Noriko; Yoshihara, Akihiro; Iwasaki, Masanori; Miyazaki, Hideo; Nakamura, Kazutoshi; Yoshie, Hiromasa

2016-03-01

Several studies have reported inconsistent results regarding the association between the PPARγPro12Ala polymorphism and obesity. Obese individuals had higher C-reactive protein (CRP) levels compared with those of normal weight, and PPARγ activation could significantly reduce serum high-sensitive CRP level. We have previously suggested that the Pro12Ala polymorphism represents a susceptibility factor for periodontitis, which is a known risk factor for increased CRP level. The aim was to investigate associations between PPARγ gene polymorphism, serum CRP level, BMI and/or periodontitis among post-menopausal Japanese women. The final sample in this study comprised 359 post-menopausal Japanese women. Periodontal parameters, including PD, CAL and BOP, were measured per tooth. PPARγPro12Ala genotype was determined by PCR-RFLP. Hs-CRP value was measured by a latex nephelometry assay. No significant differences in age, BMI or periodontal parameters were found between the genotypes. The percentages of sites with PD ≥ 4 mm were significantly higher among the hsCRP ≥ 1 mg/l group than the hsCRP periodontitis, serum CRP level or BMI in post-menopausal Japanese women. However, serum hsCRP level correlated with periodontitis in Ala allele carriers, and with BMI in non-carriers. © 2014 John Wiley & Sons A/S and The Gerodontology Society. Published by John Wiley & Sons Ltd.

The relation of serotonin-related gene and COMT gene polymorphisms with criminal behavior in schizophrenic disorder.

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Koh, Kyung Bong; Choi, Eun Hee; Lee, Young-joon; Han, Mooyoung; Choi, Sang-Sup; Kim, So Won; Lee, Min Goo

2012-02-01

It has been suggested that patients with schizophrenia might be involved in criminal behavior, such as homicidal and violent behavior. However, the relationship between criminal behavior and genes in patients with schizophrenia has not been clearly elucidated. The objective of this study was to examine the relation between criminal behavior and serotonin-related gene or catechol-O-methyltransferase (COMT) gene polymorphisms in patients with schizophrenia. Serotonin-related and COMT polymorphic markers were assessed by using single nucleotide polymorphism (SNP) genotyping. Ninety-nine crime-related inpatients with schizophrenia (57 homicidal and 42 nonhomicidal violent) and 133 healthy subjects were enrolled between October 2005 and May 2008. Diagnoses were made according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) criteria. The genotype frequencies of tryptophan hydroxylase-1 (TPH1) A218C and COMT V158M were compared between groups. The TPH1 CC genotype had 2.7-fold higher odds of crime-related schizophrenia compared with A-carrier genotype after the analysis was controlled for sex and age (OR, 2.69; 95% CI, 1.22 - 5.91; P = .01). In addition, the TPH1 CC genotype had 3.4-fold higher odds of homicidal schizophrenia compared with A-carrier genotype after the analysis was controlled for sex and age (OR, 3.38; 95% CI, 1.40 - 8.18; P = .007). However, no significant differences were found in the frequencies of genotype of COMT polymorphism between criminal schizophrenics and healthy subjects, nor were any significant differences found between nonhomicidal schizophrenics and healthy subjects. These results indicate that the TPH1 CC recessive genotype is likely to be a genetic risk factor for criminal behavior, especially homicidal behavior in patients with schizophrenia. However, COMT gene polymorphisms were not associated with criminal behavior in schizophrenic patients. © Copyright 2012 Physicians Postgraduate Press, Inc.

Prevalence of precore-defective mutant of hepatitis B virus in HBV carriers.

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Niitsuma, H; Ishii, M; Saito, Y; Miura, M; Kobayashi, K; Ohori, H; Toyota, T

1995-08-01

Two hundred and seventy-three serum specimens from hepatitis B virus (HBV) carriers were examined for the presence of a characteristic one point mutation at nucleotide (nt) 1896 from the EcoRI site of the HBV genome in the precore region (the preC mutant) using restriction fragment length polymorphism (RFLP) analysis. This assay approach could detect preC mutants or wild-type sequences when either form constituted more than 10% of the total sample. Overall, 65.5% (76/116) of HBeAg-positive carriers had only the preC wild-type. All HBeAg-positive asymptomatic carriers (n = 14) had only the preC wild-type. In patients with chronic hepatitis B and in anti-HBe-positive asymptomatic carriers, increased prevalence of the preC mutant was associated with the development of anti-HBe antibodies and normalization of the serum alanine aminotransferase concentration. Furthermore, 27 (29.0%) of 93 HBeAg-negative carriers had unexpectedly preC wild-type sequences only. Direct sequencing of the HBV precore region of HBV specimens from 24 patients revealed no mutation at nt 1896, supporting the specificity of the RFLP analysis. These results suggest that RFLP analysis was accurate for the detection of the preC mutation and that the absence of serum HBeAg cannot be explained solely by the dominance of the preC mutant.

Heteroduplex analysis of the dystrophin gene: Application to point mutation and carrier detection

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Prior, T.W.; Papp, A.C.; Snyder, P.J.; Sedra, M.S.; Western, L.M.; Bartolo, C.; Mendell, J.R. [Ohio State Univ., Columbus, OH (United States); Moxley, R.T. [Univ. of Rochester Medical Center, NY (United States)

1994-03-01

Approximately one-third of Duchenne muscular dystrophy patients have undefined mutations in the dystrophin gene. For carrier and prenatal studies in families without detectable mutations, the indirect restriction fragment length polymorphism linkage approach is used. Using a multiplex amplification and heteroduplex analysis of dystrophin exons, the authors identified nonsense mutations in two DMD patients. Although the nonsense mutations are predicted to severely truncate the dystrophin protein, both patients presented with mild clinical courses of the disease. As a result of identifying the mutation in the affected boys, direct carrier studies by heteroduplex analysis were extended to other relatives. The authors conclude that the technique is not only ideal for mutation detection but is also useful for diagnostic testing. 29 refs., 4 figs.

GCH1-polymorphism and pain sensitivity among women with provoked vestibulodynia

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Heddini Ulrika

2012-09-01

Full Text Available Abstract Background Provoked vestibulodynia (PVD is a pain disorder localized in the vestibular mucosa. It is the most common cause of dyspareunia among young women and it is associated with general pain hypersensitivity and other chronic pain conditions. Polymorphism in the guanosine triphosphate cyclohydrolase (GCH1 gene has been found to influence general pain sensitivity and the risk of developing a longstanding pain condition. The aim of this study was to investigate GCH1-polymorphism in women with PVD and healthy controls, in correlation to pain sensitivity. Results We found no correlation between the previously defined pain-protective GCH1-SNP combination and the diagnosis of PVD. Nor any correlation with pain sensitivity measured as pressure pain thresholds on the arm, leg and in the vestibule, coital pain scored on a visual analog scale and prevalence of other bodily pain conditions among women with PVD (n = 98 and healthy controls (n = 102. However, among patients with current treatment (n = 36, there was a significant interaction effect of GCH1-gene polymorphism and hormonal contraceptive (HC therapy on coital pain (p = 0.04 as well as on pressure pain thresholds on the arm (p = 0.04. PVD patients carrying the specified SNP combination and using HCs had higher pain sensitivity compared to non-carriers. In non-HC-users, carriers had lower pain sensitivity. Conclusions The results of this study gave no support to the hypothesis that polymorphism in the GCH1-gene contributes to the etiology of PVD. However, among patients currently receiving treatment an interaction effect of the defined SNP combination and use of hormonal contraceptives on pain sensitivity was found. This finding offers a possible explanation to the clinically known fact that some PVD patients improve after cessation of hormonal contraceptives, indicating that PVD patients carrying the defined SNP combination of GCH1 would benefit from this

PPARγ Pro12Ala polymorphism and risk of acute coronary syndrome in a prospective study of Danes

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Jensen Majken K

2009-06-01

Full Text Available Abstract Background Acute coronary syndrome (ACS is a major cause of morbidity and mortality in the western world. Peroxisome proliferator-activated receptor γ (PPARγ plays a key role in the regulation of the energy balance, adipocyte differentiation and lipid biosynthesis. The aim was to investigate if the polymorphism PPARγ2 Pro12Ala, which encodes a less efficient transcription factor, was associated with risk of acute coronary disease and if there were interactions between this polymorphism and factors that modify PPARγ activity, such as alcohol intake, smoking, and use of non-steroidal anti-inflammatory medicine. Methods A case-cohort study including 1031 ACS cases and a sub-cohort of 1703 persons was nested within the population-based prospective study Diet, Cancer and Health of 57,053 individuals. Results Homozygous male variant allele carriers of PPARγ2 Pro12Ala were at higher risk of ACS (HR = 2.12, 95% CI: 1.00–4.48 than homozygous carriers of the Pro-allele. Among men, there was a statistically significant interaction between genotypes and alcohol intake such that homozygous variant allele carriers with a low alcohol intake were at higher risk of ACS (HR = 25.3, CI: 16.5–38.7 compared to homozygous common allele carriers (p for interaction Conclusion In the present study, there were no consistent associations between PPARγ Pro12Ala and risk of ACS, and no consistent interaction with alcohol, BMI, NSAID or smoking in relation to ACS.

Matrix Metalloproteinases Polymorphisms as Prognostic Biomarkers in Malignant Pleural Mesothelioma

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Danijela Štrbac

2017-01-01

Full Text Available Background. Malignant pleural mesothelioma (MPM is a rare disease with a relatively short overall survival (OS. Metalloproteinases (MMPs have a vast biological effect on tumor progression, invasion, metastasis formation, and apoptosis. MMP expression was previously associated with survival in MPM. Our aim was to evaluate if genetic variability of MMP genes could also serve as a prognostic biomarker in MPM. Methods. We genotyped 199 MPM patients for ten polymorphisms: rs243865, rs243849 and rs7201, in MMP2; rs17576, rs17577, rs20544, and rs2250889 in MMP9; and rs1042703, rs1042704, and rs743257 in MMP14. We determined the influence on survival using Cox regression. Results. Carriers of polymorphic MMP9 rs2250889 allele had shorter time to progression (TTP (6.07 versus 10.03 months, HR = 2.45, 95% CI = 1.45–4.14, p=0.001 and OS (9.23 versus 19.2 months, HR = 2.39, 95% CI = 1.37–4.18, p=0.002. In contrast, carriers of at least one polymorphic MMP9 rs20544 allele had longer TTP (10.93 versus 9.40 months, HR = 0.57, 95% CI = 0.38–0.86 p=0.007 and OS (20.67 versus 13.50 months, HR = 0.56, 95% CI = 0.37–0.85, p=0.007. MMP14 rs1042703 was associated with nominally shorter TTP (8.7 versus 9.27 months, HR = 2.09, 95% CI = 1.06–4.12, p=0.032. Conclusions. Selected MMP SNPs were associated with survival and could be used as potential genetic biomarkers in MPM.

PPARA intron polymorphism associated with power performance in 30-s anaerobic Wingate Test.

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Miroslav Petr

Full Text Available To date, polymorphisms in several genes have been associated with a strength/power performance including alpha 3 actinin, ciliary neurotrophic factor, vitamin D receptor, or angiotensin I converting enzyme, underlining the importance of genetic component of the multifactorial strength/power-related phenotypes. The single nucleotide variation in peroxisome proliferator-activated receptor alpha gene (PPARA intron 7 G/C (rs4253778; g.46630634G>C has been repeatedly found to play a significant role in response to different types of physical activity. We investigated the effect of PPARA intron 7 G/C polymorphism specifically on anaerobic power output in a group of 77 elite male Czech ice hockey players (18-36 y. We determined the relative peak power per body weight (Pmax.kg(-1 and relative peak power per fat free mass (W.kg(-1FFM during the 30-second Wingate Test (WT30 on bicycle ergometer (Monark 894E Peak bike, MONARK, Sweden. All WT30s were performed during the hockey season. Overall genotype frequencies were 50.6% GG homozygotes, 40.3% CG heterozygotes, and 9.1% CC homozygotes. We found statistically significant differences in Pmax.kg(-1 and marginally significant differences in Pmax.kg(-1FFM values in WT30 between carriers and non-carriers for C allele (14.6 ± 0.2 vs. 13.9 ± 0.3 W.kg(-1 and 15.8 ± 0.2 vs. 15.2 ± 0.3 W.kg(-1FFM, P = 0.036 and 0.12, respectively. Furthermore, Pmax.kg(-1FFM strongly positively correlated with the body weight only in individuals with GG genotypes (R = 0.55; p<0.001. Our results indicate that PPARA 7C carriers exhibited higher speed strength measures in WT30. We hypothesize that C allele carriers within the cohort of trained individuals may possess a metabolic advantage towards anaerobic metabolism.

Contextual fear conditioning in virtual reality is affected by 5HTTLPR and NPSR1 polymorphisms: effects on fear-potentiated startle

Directory of Open Access Journals (Sweden)

Evelyn eGlotzbach-Schoon

2013-04-01

Full Text Available The serotonin (5-HT and neuropeptide S (NPS systems are discussed as important genetic modulators of fear and sustained anxiety contributing to the etiology of anxiety disorders. Sustained anxiety is a crucial characteristic of most anxiety disorders which likely develops through context conditioning. This study investigated if and how genetic alterations of the 5-HT and the NPS systems as well as their interaction modulate contextual fear conditioning; specifically, function polymorphic variants in the genes coding for the 5-HT transporter (5HTT and the NPS receptor (NPSR1 were studied. A large group of healthy volunteers was therefore stratified for 5HTTLPR (S+ vs. LL carriers and NPSR1 rs324981 (T+ vs. AA carriers polymorphisms resulting in four genotype groups (S+/T+, S+/AA, LL/T+, LL/AA of 20 participants each. All participants underwent contextual fear conditioning and extinction using a virtual reality paradigm. During acquisition, one virtual office room (anxiety context, CXT+ was paired with an unpredictable electric stimulus (unconditioned stimulus, US, whereas another virtual office room was not paired with any US (safety context, CXT-. During extinction no US was administered. Anxiety responses were quantified by fear-potentiated startle and ratings. Most importantly, we found a gene × gene interaction on fear-potentiated startle. Only carriers of both risk alleles (S+/T+ exhibited higher startle responses in CXT+ compared to CXT-. In contrast, anxiety ratings were only influenced by the NPSR1 polymorphism with AA carriers showing higher anxiety ratings in CXT+ as compared to CXT-. Our results speak in favor of a two level account of fear conditioning with diverging effects on implicit vs. explicit fear responses. Contextual fear reflected in potentiated startle responses may be an endophenotype for anxiety disorders.

Association between Polymorphisms in Glutathione Peroxidase and Selenoprotein P Genes, Glutathione Peroxidase Activity, HRT Use and Breast Cancer Risk

DEFF Research Database (Denmark)

Méplan, Catherine; Dragsted, Lars Ove; Ravn-Haren, Gitte

2013-01-01

Breast cancer (BC) is one of the most common cancers in women. Evidence suggests that genetic variation in antioxidant enzymes could influence BC risk, but to date the relationship between selenoproteins and BC risk remains unclear. In this report, a study population including 975 Danish cases...... and 975 controls matched for age and hormone replacement therapy (HRT) use was genotyped for five functional single nucleotide polymorphisms (SNPs) in SEPP1, GPX1, GPX4 and the antioxidant enzyme SOD2 genes. The influence of genetic polymorphisms on breast cancer risk was assessed using conditional...... logistic regression. Additionally pre-diagnosis erythrocyte GPx (eGPx) activity was measured in a sub-group of the population. A 60% reduction in risk of developing overall BC and ductal BC was observed in women who were homozygous Thr carriers for SEPP1 rs3877899. Additionally, Leu carriers for GPX1 Pro...

Gender dependent association between perinatal morbidity and estrogen receptor-alpha Pvull polymorphism.

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Derzbach, László; Treszl, András; Balogh, Adám; Vásárhelyi, Barna; Tulassay, Tivadar; Rigó J, János

2005-01-01

Assuming the importance of estrogen in perinatal physiology, we tested the association of an estrogen receptor-alpha (ER-alpha) gene Pvull pP polymorphism with perinatal morbidity in premature infants. The ER-alpha Pp genotype was determined in 69 low-birth weight (LBW) boys and 72 LBW girls, 86 term boys and 81 term girls. The association between risk factors, genotype, gender and perinatal morbidity was tested with binary logistic regression analysis. Boys carrying "p" allele were at lower risk for necrotizing enterocolitis (OR [95% Cl]: 0.24 [0.07-0.83]) and patent ductus arteriosus (OR [95% Cl]: 0.24 [0.05-0.97]). The carrier state of the "p" allele was associated with a 34-h shorter period of oxygen supplementation on average (P=0.0018). Boys with pp genotype were at greater risk for intraventricular hemorrhage (OR [95% Cl]: 4.39 [1.15-16.82]). No association between ER-alpha Pvull polymorphism and morbidity was present in girls. Since homozygocity for any Pvull alleles (i.e. having PP or pp genotype) increases the risk for at least one of the most common perinatal complications, it is likely that the heterozygous carrier state of Pvull genotypes has a protective effect, which is gender-dependent.

Polymorphism in the retinoic acid metabolizing enzyme CYP26B1 and the development of Crohn's Disease.

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Karin Fransén

Full Text Available Several studies suggest that Vitamin A may be involved in the pathogenesis of inflammatory bowel disease (IBD, but the mechanism is still unknown. Cytochrome P450 26 B1 (CYP26B1 is involved in the degradation of retinoic acid and the polymorphism rs2241057 has an elevated catabolic function of retinoic acid, why we hypothesized that the rs2241057 polymorphism may affect the risk of Crohn's disease (CD and Ulcerative Colitis (UC. DNA from 1378 IBD patients, divided into 871 patients with CD and 507 with UC, and 1205 healthy controls collected at Örebro University Hospital and Karolinska University Hospital were analyzed for the CYP26B1 rs2241057 polymorphism with TaqMan® SNP Genotyping Assay followed by allelic discrimination analysis. A higher frequency of patients homozygous for the major (T allele was associated with CD but not UC compared to the frequency found in healthy controls. A significant association between the major allele and non-stricturing, non-penetrating phenotype was evident for CD. However, the observed associations reached borderline significance only, after correcting for multiple testing. We suggest that homozygous carriers of the major (T allele, relative to homozygous carriers of the minor (C allele, of the CYP26B1 polymorphism rs2241057 may have an increased risk for the development of CD, which possibly may be due to elevated levels of retinoic acid. Our data may support the role of Vitamin A in the pathophysiology of CD, but the exact mechanisms remain to be elucidated.

The BDNF Val66Met polymorphism affects HPA-axis reactivity to acute stress.

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Alexander, Nina; Osinsky, Roman; Schmitz, Anja; Mueller, Eva; Kuepper, Yvonne; Hennig, Juergen

2010-07-01

Growing evidence suggests that individual differences in HPA-axis reactivity to psychosocial stress are partly due to heritable influences. However, knowledge about the role of specific genetic variants remains very limited to date. Since brain-derived neurotrophic factor (BDNF) not only exhibits neurotrophic actions but is also involved in the regulation of hypothalamic neuropeptides, we investigated the role of a common functional polymorphism within the BDNF gene (BDNF Val66Met) in the context of endocrine and cardiovascular stress reactivity. Healthy male adults (N=100) were genotyped and exposed to a standardized laboratory stress task (Public Speaking). Saliva cortisol and self-reported mood levels were obtained at 6 time points prior to the stressor and during an extended recovery period. Furthermore, heart rate reactivity as an indicator of sympathetic activation was monitored continuously during the experimental procedure. We report a small, but significant effect of the BDNF Val66Met polymorphism on stress reactivity. More precisely, carriers of the met-allele showed a significantly attenuated HPA-axis and cardiovascular reactivity to the psychosocial stressor compared to subjects with the val/val genotype. Furthermore, the diminished physiological response in met-allele carriers was also attended by significantly lower self-reported ratings of perceived stress and nervousness. Our findings of a diminished endocrine and cardiovascular stress response in healthy male adults is consistent with a previously published study and adds further evidence for a crucial role of the BDNF Val66Met polymorphism in the modulation of stress reactivity. Copyright 2010. Published by Elsevier Ltd.

BDNF Val66Met polymorphism as a moderator of exercise enhancement of smoking cessation treatment in anxiety vulnerable adults

NARCIS (Netherlands)

Smits, J.A.J.; Powers, M.B.; Rosenfield, D.; Zvolensky, M.J.; Jacquart, J.; Davis, M.L.; Beevers, C.G.; Marcus, B.H.; Church, T.S.; Otto, M.W.

2016-01-01

Background: Exercise interventions facilitate the odds of quit success among high-anxiety sensitive adults smokers. We examined the dependency of these benefits on the genetic BDNF Val66Met (rs6265) polymorphism; individuals who are Met carriers have lower BDNF responses and reduced associated

Polymorphisms in the vitamin D Receptor (VDR and the risk of ovarian cancer: a meta-analysis.

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Yanling Liu

Full Text Available The vitamin D receptor (VDR principally mediates the anticancer activities of vitamin D. Various epidemiological studies have investigated the associations of VDR gene polymorphisms with ovarian cancer; however, the results have been inconclusive. In the current study, we evaluated, in a meta-analysis, the association of five common single nucleotide polymorphisms (SNPs in the VDR gene (ApaI, BsmI, Cdx-2, FokI, and TaqI with the risk of ovarian cancer. Six eligible studies, with a total of 4,107 cases and 6,661 controls, which evaluated the association of these variants and ovarian cancer risk, were identified from the MEDLINE and PubMed databases. The meta-analysis indicated that FokI was associated with an increased ovarian cancer risk, with a pooled odds ratio (OR of 1.10 [95% confidence intervals (95% CI = 1.00-1.20] for CT heterozygotes and 1.16 (95% CI = 1.02-1.30 for TT homozygotes relative to common CC carriers. Carriers of the T allele (also known as the f allele showed an 11% (pooled OR = 1.11, 95% CI = 1.02-1.21; TT/CT vs. CC increased risk of ovarian cancer relative to CC carriers. For FokI, no significant heterogeneity between the studies was found (I(2 = 0%, P = 0.62 for the Q test. There was no statistically significant association between the other four variants (ApaI, BsmI, Cdx-2 and TaqI and risk of ovarian cancer. These data indicate that the polymorphism FokI on the VDR is a susceptibility factor for ovarian cancer. Nevertheless, more studies are warranted to elucidate the underlying mechanisms of the VDR in development of ovarian cancer.

Effect of common polymorphisms of the farnesoid X receptor and bile acid transporters on the pharmacokinetics of ursodeoxycholic acid.

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Hu, Miao; Fok, Benny S P; Wo, Siu-Kwan; Lee, Vincent H L; Zuo, Zhong; Tomlinson, Brian

2016-01-01

Ursodeoxycholic acid (UDCA), a natural, dihydroxy bile acid, promotes gallstone dissolution and has been attributed with several other beneficial effects. The farnesoid X receptor (FXR) may influence the pharmacokinetics of UDCA by modulating the expression of bile acid transporters. This exploratory study examined whether common functional polymorphisms in FXR and in bile acid transporter genes affect the pharmacokinetics of exogenous UDCA. Polymorphisms in genes for transporters involved in bile acid transport, solute carrier organic anion 1B1 (SLCO1B1) 388A>G and 521T>C, solute carrier 10A1 (SLC10A1) 800 C>T and ATP-binding cassette B11 (ABCB11) 1331T>C, and the FXR -1G>T polymorphism were genotyped in 26 male Chinese subjects who ingested single oral 500-mg doses of UDCA. Plasma concentrations of UDCA and its major conjugate metabolite glycoursodeoxycholic acid (GUDCA) were determined. The mean systemic exposure of UDCA was higher in the five subjects with one copy of the FXR -1G>T variant allele than in those homozygous for the wild-type allele (n = 21) (AUC0-24 h : 38.5 ± 28.2 vs. 20.9 ± 8.0 μg h/mL, P = 0.021), but this difference appeared mainly due to one outlier with the -1GT genotype and elevated baseline and post-treatment UDCA concentrations. After excluding the outlier, body weight was the only factor associated with plasma concentrations of UDCA and there were no significant associations with the other polymorphisms examined. None of the polymorphisms affected the pharmacokinetics of GUDCA. This study showed that the common polymorphisms in bile acid transporters had no significant effect on the pharmacokinetics of exogenous UDCA but an effect of the FXR polymorphism cannot be excluded. © 2015 Wiley Publishing Asia Pty Ltd.

[THE INFLUENCE OF SEROTONIN TRANSPORTER AND MONOAMINE OXIDASE A GENES POLYMORPHISM ON PSYCHO-EMOTION AND KARYOLOGICAL STABILITY OF ATHLETES].

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Kalaev, V N; Nechaeva, M S; Korneeva, O S; Cherenkov, D A

2015-11-01

The influence of polymorphism of the serotonin transporter and monoamine oxidase A genes, associated with man's aggressiveness on the psycho-emotional state and karyological status of single combat athletes. It was revealed that the carriers of less active ("short"), monoamine oxidase A gene variant have a high motivation to succeed and less rigidity and frustrated, compared to the carriers of more active ("long") version of the gene. Heterozygote carriers of less active ("short") variant of the serotonin transporter gene 5-HTTL had more physical aggression, guilt and were less frustrated compared with carriers of two long alleles. It has been revealed the association of studied genes with the karyological status of athletes. So fighters who are carriers of the short and long alleles of the serotonin transporter gene had more cells with nuclear abnormalities in the buccal epithelium than single combat athletes which both alleles were long.

The Role of the Val66Met Polymorphism of the Brain Derived Neurotrophic Factor Gene in Coping Strategies Relevant to Depressive Symptoms.

Directory of Open Access Journals (Sweden)

Warren Caldwell

Full Text Available Disturbances of brain derived neurotrophic factor (BDNF signalling have been implicated in the evolution of depression, which likely arises, in part, as a result of diminished synaptic plasticity. Predictably, given stressor involvement in depression, BDNF is affected by recent stressors as well as stressors such as neglect experienced in early life. The effects of early life maltreatment in altering BDNF signalling may be particularly apparent among those individuals with specific BDNF polymorphisms. We examined whether polymorphisms of the Val66Met genotype might be influential in moderating how early-life events play out with respect to later coping styles, cognitive flexibility and depressive features. Among male and female undergraduate students (N = 124, childhood neglect was highly related to subsequent depressive symptoms. This outcome was moderated by the BDNF polymorphism in the sense that depressive symptoms appeared higher in Met carriers who reported low levels of neglect than in those with the Val/Val allele. However, under conditions of high neglect depressive symptoms only increased in the Val/Val individuals. In effect, the Met polymorphism was associated with depressive features, but did not interact with early life neglect in predicting later depressive features. It was further observed that among the Val/Val individuals, the relationship between neglect and depression was mediated by emotion-focused styles and diminished perceived control, whereas this mediation was not apparent in Met carriers. In contrast to the more typical view regarding this polymorphism, the data are consistent with the perspective that in the presence of synaptic plasticity presumably associated with the Val/Val genotype, neglect allows for the emergence of specific appraisal and coping styles, which are tied to depression. In the case of the reduced degree of neuroplasticity expected in the Met carriers, early life adverse experiences are not tied

Possible association between serotonin transporter promoter region polymorphism and extremely violent crime in Chinese males.

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Liao, Ding-Lieh; Hong, Chen-Jee; Shih, Hao-Ling; Tsai, Shih-Jen

2004-01-01

The neurotransmitter, serotonin, has been implicated in aggressive behavior. The serotonin transporter (5-HTT), which reuptakes serotonin into the nerve terminal, plays a critical role in the regulation of serotonergic function. Previous western reports have demonstrated that the low-activity short (S) allele of the 5-HTT gene-linked polymorphic-region (5-HTTLPR) polymorphism is associated with aggressive behavior and associated personality traits. In the present study, we investigated this 5-HTTLPR genetic polymorphism in a group of Chinese males who had been convicted for extremely violent crime (n = 135) and a normal control group (n = 111). The proportion of S-allele carriers was significantly higher in the criminal group than in the controls (p = 0.006). A significant association was not demonstrated for the relationship between the 5-HTTLPR polymorphism and antisocial personality disorder, substance abuse or alcohol abuse in the criminal group. Our findings demonstrate that carriage of the low-activity S allele is associated with extremely violent criminal behavior in Chinese males, and suggests that the 5-HTT may be implicated in the mechanisms underlying violent behaviors.

Cancer protection elicited by a single nucleotide polymorphism close to the adrenomedullin gene.

Science.gov (United States)

Martínez-Herrero, Sonia; Martínez, Alfredo

2013-04-01

The risk of developing cancer is regulated by genetic variants, including polymorphisms. Characterizing such variants may help in developing protocols for personalized medicine. Adrenomedullin is a regulatory peptide involved in cancer promotion and progression. Carriers of a single nucleotide polymorphism (SNP) in the proximity of the adrenomedullin gene have lower levels of circulating peptide. The aim of the present work was to investigate whether carriers of this SNP (rs4910118) are protected against cancer. This was a retrospective study. DNA samples were obtained from the Carlos III DNA National Bank (University of Salamanca, Salamanca, Spain). Samples represent a variety of donors and patients from Spain. DNA from patients with breast cancer (n = 238), patients with lung cancer (n = 348), patients with cardiac insufficiency (n = 474), and healthy donors of advanced age (n = 500) was used. All samples were genotyped using double-mismatch PCR, and confirmation was achieved by direct sequencing. The minor allele frequency was calculated in all groups. The Pearson χ(2) was used to compare SNP frequencies. Of 1560 samples, 14 had the minor allele, with a minor allele frequency in healthy donors of 0.90%. Patients with cancer had a statistically significantly lower frequency than healthy donors (odds ratio = 0.216, 95% confidence interval = 0.048-0.967, P = .028). Carriers of the minor allele have a 4.6-fold lower risk of developing cancer than homozygotes for the major allele. Knowledge of the rs4910118 genotype may be useful for stratifying patients in clinical trials and for designing prevention strategies.

DNA Glycosylases Involved in Base Excision Repair May Be Associated with Cancer Risk in BRCA1 and BRCA2 Mutation Carriers

NARCIS (Netherlands)

A. Osorio (Ana); R.L. Milne (Roger); K.B. Kuchenbaecker (Karoline); T. Vaclová (Tereza); G. Pita (Guillermo); R. Alonso (Rosario); P. Peterlongo (Paolo); I. Blanco (Ignacio); M. de La Hoya (Miguel); M. Durán (Mercedes); O. Díez (Orland); T. Ramon Y Cajal; I. Konstantopoulou (I.); C. Martínez-Bouzas (Cristina); R. Andrés Conejero (Raquel); P. Soucy (Penny); L. McGuffog (Lesley); D. Barrowdale (Daniel); A. Lee (Andrew); B. Arver (Brita Wasteson); J. Rantala (Johanna); N. Loman (Niklas); H. Ehrencrona (Hans); O.I. Olopade (Olofunmilayo); M.S. Beattie (Mary); S.M. Domchek (Susan); K.L. Nathanson (Katherine); R. Rebbeck (Timothy); B.K. Arun (Banu); B.Y. Karlan (Beth); C.S. Walsh (Christine); K.J. Lester (Kathryn); E.M. John (Esther); A.S. Whittemore (Alice); M.B. Daly (Mary); M.C. Southey (Melissa); J.L. Hopper (John); M.-B. Terry (Mary-Beth); S.S. Buys (Saundra); R. Janavicius (Ramunas); C.M. Dorfling (Cecilia); E.J. van Rensburg (Elizabeth); L. Steele (Linda); S.L. Neuhausen (Susan); Y.C. Ding (Yuan); T.V.O. Hansen (Thomas); L. Jønson (Lars); B. Ejlertsen (Bent); A-M. Gerdes (Anne-Marie); J. Infante (Jon); B. Herráez (Belén); L.T. Moreno (Leticia Thais); J.N. Weitzel (Jeffrey); J. Herzog (Josef); K. Weeman (Kisa); S. Manoukian (Siranoush); B. Peissel (Bernard); D. Zaffaroni (D.); G. Scuvera (Giulietta); B. Bonnani (Bernardo); F. Mariette (F.); S. Volorio (Sara); A. Viel (Alessandra); L. Varesco (Liliana); L. Papi (Laura); L. Ottini (Laura); M.G. Tibiletti (Maria Grazia); P. Radice (Paolo); D. Yannoukakos (Drakoulis); J. Garber; S.D. Ellis (Steve); D. Frost (Debra); R. Platte (Radka); E. Fineberg (Elena); D.G. Evans (Gareth); F. Lalloo (Fiona); L. Izatt (Louise); R. Eeles (Rosalind); J.W. Adlard (Julian); R. Davidson (Rosemarie); T.J. Cole (Trevor); D. Eccles (Diana); J. Cook (Jackie); S.V. Hodgson (Shirley); C. Brewer (Carole); M. Tischkowitz (Marc); F. Douglas (Fiona); M.E. Porteous (Mary); L. Side (Lucy); L.J. Walker (Lisa); P.J. Morrison (Patrick); A. Donaldson (Alan); J. Kennedy (John); C. Foo (Claire); A.K. Godwin (Andrew); R.K. Schmutzler (Rita); B. Wapenschmidt (Barbara); K. Rhiem (Kerstin); C.W. Engel (Christoph); A. Meindl (Alfons); N. Ditsch (Nina); N. Arnold (Norbert); H. Plendl (Hansjoerg); D. Niederacher (Dieter); C. Sutter (Christian); S. Wang-Gohrke (Shan); D. Steinemann (Doris); S. Preisler-Adams (Sabine); K. Kast (Karin); R. Varon-Mateeva (Raymonda); P.A. Gehrig (Paola A.); D. Stoppa-Lyonnet (Dominique); O. Sinilnikova (Olga); S. Mazoyer (Sylvie); F. Damiola (Francesca); B. Poppe (Bruce); K. Claes (Kathleen); M. Piedmonte (Marion); K. Tucker (Kathryn); F.J. Backes (Floor); P.M. Rodríguez; W. Brewster (Wendy); K. Wakeley (Katie); T. Rutherford (Thomas); T. Caldes (Trinidad); H. Nevanlinna (Heli); K. Aittomäki (Kristiina); M.A. Rookus (Matti); T.A.M. van Os (Theo); L. van der Kolk (Lizet); J.L. de Lange (J.); E.J. Meijers-Heijboer (Hanne); A.H. van der Hout (Annemarie); C.J. van Asperen (Christi); E.B. Gómez García (Encarna); N. Hoogerbrugge (Nicoline); J.M. Collée (Margriet); C.H.M. van Deurzen (Carolien); R.B. van der Luijt (Rob); P. Devilee (Peter); E. Olah (Edith); C. Lazaro (Conxi); A. Teulé (A.); M. Menéndez (Mireia); A. Jakubowska (Anna); C. Cybulski (Cezary); J. Gronwald (Jacek); J. Lubinski (Jan); K. Durda (Katarzyna); K. Jaworska-Bieniek (Katarzyna); O.T. Johannson (Oskar); C. Maugard; M. Montagna (Marco); S. Tognazzo (Silvia); P.J. Teixeira; S. Healey (Sue); C. Olswold (Curtis); L. Guidugli (Lucia); N.M. Lindor (Noralane); S. Slager (Susan); C. Szabo (Csilla); J. Vijai (Joseph); M. Robson (Mark); N. Kauff (Noah); L. Zhang (Lingling); R. Rau-Murthy (Rohini); A. Fink-Retter (Anneliese); C.F. Singer (Christian); C. Rappaport (Christine); D. Geschwantler Kaulich (Daphne); G. Pfeiler (Georg); M.-K. Tea; A. Berger (Annemarie); C. Phelan (Catherine); M.H. Greene (Mark); P.L. Mai (Phuong); F. Lejbkowicz (Flavio); I.L. Andrulis (Irene); A.M. Mulligan (Anna Marie); G. Glendon (Gord); A.E. Toland (Amanda); S.E. Bojesen (Stig); I.S. Pedersen (Inge Sokilde); L. Sunde (Lone); M. Thomassen (Mads); T.A. Kruse (Torben); U.B. Jensen; E. Friedman (Eitan); Y. Laitman (Yael); S.P. Shimon (Shani Paluch); J. Simard (Jacques); D.F. Easton (Douglas); K. Offit (Kenneth); F.J. Couch (Fergus); G. Chenevix-Trench (Georgia); A.C. Antoniou (Antonis); J. Benítez (Javier)

2014-01-01

textabstractSingle Nucleotide Polymorphisms (SNPs) in genes involved in the DNA Base Excision Repair (BER) pathway could be associated with cancer risk in carriers of mutations in the high-penetrance susceptibility genes BRCA1 and BRCA2, given the relation of synthetic lethality that exists between

Polymorphisms in genes involved in GH1 release and their association with breast cancer risk.

Science.gov (United States)

Wagner, Kerstin; Hemminki, Kari; Grzybowska, Ewa; Klaes, Rüdiger; Burwinkel, Barbara; Bugert, Peter; Schmutzler, Rita K; Wappenschmidt, Barbara; Butkiewicz, Dorota; Pamula, Jolanta; Pekala, Wioletta; Försti, Asta

2006-09-01

The regulation of growth hormone 1 (GH1) and insulin-like-growth factor-1 (IGF-1) release is under the influence of three pituitary hormones [growth hormone releasing hormone (GHRH), ghrelin (GHRL) and somatostatin (SST)], which act in an autocrine/paracrine fashion in the breast. By binding to their respective receptors, they control cell proliferation, differentiation and apoptosis in a GH1/IGF-1-dependent manner. We investigated single nucleotide polymorphisms (SNPs) in the GHRH, GHRHR, GHRL, GHSR, SST and SSTR2 gene regions in a Polish and a German cohort of 798 breast cancer cases and 1011 controls. Our study revealed an association of a novel TC repeat polymorphism in the SST promoter with a decreased breast cancer risk in the Polish study population [odds ratio (OR), 0.65; 95% confidence interval (CI), 0.44-0.96]. The closely linked SNP IVS1 A+46G showed the same trend. For both polymorphisms the association was stronger in women above the age of 50 (OR, 0.33; 95% CI, 0.14-0.76 and OR, 0.39; 95% CI, 0.18-0.87, respectively). The protective effect of these polymorphisms was confirmed in a haplotype analysis among women above 50 years of age and carrying the two variant alleles (OR, 0.37; 95% CI, 0.17-0.80). In the independent German population, we observed slightly decreased ORs among women above the age of 50 years. In the SSTR2 gene, carriers of the promoter 21/21 TG repeat genotype were at a decreased breast cancer risk (OR, 0.62; 95% CI, 0.41-0.94) compared to carriers of the other genotypes in the Polish population. Furthermore, we identified a protective effect of the GHRHR C-261T SNP in both populations (joint analysis CT+TT versus CC: OR, 0.80; 95% CI, 0.65-0.99). This effect was carried by a haplotype containing the protective allele. Thus, our study concludes a possible protective influence of distinct polymorphisms in genes involved in GH1 release on breast cancer risk.

[Association of T174M polymorphism of the angiotensinogen gene with the higher risk of cerebral stroke in women].

Science.gov (United States)

Stetskaia, T A; Bushueva, O Iu; Bulgakova, I V; Vialykh, E K; Shuteeva, T V; Biriukov, A E; Ivanov, V P; Polonikov, A V

2014-01-01

To study the association of M235T (rs699) and T174M (rs4762) polymorphisms of the angiotensinogen (AGT) gene with the risk of cerebral stroke (CS) in the Russians of the Central Chernozem Region. A total of 638 DNA samples obtained from 353 patients with CS and 285 sex- and age-matched healthy individuals were examined. The polymorphisms were genotyped by polymerase chain reaction (T174M) and TaqMan allelic discrimination (M235T) assays. Heterozygous AGT 174TM genotype carriers were found to be at a higher risk for CS (odd ratio (OR) = 1.52; 95% confidence interval (CI), 1.08-2.15; p = 0.02). A gender-stratified analysis showed that the mutant 174M allele (OR = 1.86; 95% CI, 1.14-3.03, p = 0.01) and variant 174TM and 174MM genotypes (OR = 1.86; 95% CI, 1.09-3.20; p = 0.02) were associated with the higher risk of cerebral stroke in women. The association of AGT T174M polymorphism with the risk of CS was first found; but the higher risk of the disease in the carriers of variant alleles and genotypes was observed in the women only.

COMT and MTHFR polymorphisms interaction on cognition in schizophrenia: an exploratory study.

Science.gov (United States)

Kontis, Dimitrios; Theochari, Eirini; Fryssira, Helen; Kleisas, Spyridon; Sofocleous, Christalena; Andreopoulou, Angeliki; Kalogerakou, Stamatina; Gazi, Anthia; Boniatsi, Lucia; Chaidemenos, Alexandros; Tsaltas, Eleftheria

2013-03-14

The investigation of the catechol-O-methyltransferase (COMT-[rs4680]) and methylenetetrahydrofolate reductase (MTHFR-[rs1801133]) polymorphisms' interaction might shed light into the pathogenetic mechanisms of the cognitive dysfunction in schizophrenia. In an exploratory study, we hypothesized that the MTHFR 677T allele which has been related to a hypoactive MTHFR enzyme would augment the unfavorable effects of COMT Val158 homozygosity which has been associated with COMT enzyme hyperfunction. 90 schizophrenia patients and 55 healthy volunteers were assessed on psychomotor speed, pattern and spatial recognition memory (SRM), spatial working memory (SWM), attentional flexibility and planning (Stockings of Cambridge-SOC). IQ scores in a random subgroup of patients were also measured. A significant COMT×MTHFR interaction on SWM (p=0.048) and planning (p=0.026) was revealed in both groups. Among COMT-Val/Val participants, MTHFR-C/C made more SWM errors (p=0.033) and solved fewer SOC problems (p=0.025) than MTHFR-T carriers. In patients, there was a significant COMT×MTHFR interaction on full scale IQ (p=0.035): among COMT-Met carriers, MTHFR-T carriers performed significantly worse than MTHFR-C/C (p=0.021), which was driven by a COMT×MTHFR interaction involving performance IQ (p=0.047). In conclusion, COMT and MTHFR polymorphisms interacted on cognition, suggesting that the MTHFR enzyme activity might moderate the effects of the COMT enzyme. In contrast to our initial hypothesis, the MTHFR T-allele attenuated the cognitive effects of COMT Val homozygosity. In this preliminary study, we propose that dopaminergic and intracellular methylation mechanisms could interact on cognitive deficits in schizophrenia. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Association between ABCG2 and SLCO1B1 polymorphisms and adverse drug reactions to regorafenib: a preliminary study
.

Science.gov (United States)

Maeda, Akimitsu; Ando, Hitoshi; Ura, Takashi; Komori, Azusa; Hasegawa, Ayako; Taniguchi, Hiroya; Kadowaki, Shigenori; Muro, Kei; Tajika, Masahiro; Kobara, Makiko; Matsuzaki, Masahide; Hashimoto, Naoya; Maeda, Mieko; Kojima, Yasushi; Aoki, Masahiro; Kondo, Eisaku; Mizutani, Akiyoshi; Fujimura, Akio

2017-05-01

Due to the occurrence of severe adverse drug reactions to regorafenib, a drug used in cancer therapy, the identification of a predictive marker(s) is needed to increase the therapeutic applicability of this compound. We therefore investigated whether polymorphisms in the ABCG2 and SLCO1B genes are associated with adverse drug reactions to regorafenib. For these analyses, 37 Japanese cancer patients were treated with regorafenib, genotyped for polymorphisms in ABCG2 and SLCO1B, and evaluated for drug-related adverse drug reactions. There was no association between the ABCG2 421C>A variant and adverse drug reactions to regorafenib. After treatment, the incidences of increased aspartate aminotransferase (AST) and alanine aminotransferase (ALT) as well as increased total bilirubin (grade ≥ 2) were 8%, 4%, and 12%, and 42%, 25%, and 25% among SLCO1B1*1b carriers and non-carriers, respectively. There were no significant associations between elevated ALT and bilirubin and the SLCO1B1*1b allele. However, there were significantly lower incidences of increased AST (8% vs. 42%) and anemia (16% vs. 50%) in SLCO1B1*1b carriers than in non-carriers. The absence of SLCO1B1*1b allele appears to be associated with the development of adverse drug reactions to regorafenib; however, further studies involving larger test groups and other populations are needed to confirm these findings.
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Polymorphisms of the OXTR Gene Explain Why Sales Professionals Love to Help Customers

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Willem J.M.I. Verbeke

2013-11-01

Full Text Available Polymorphisms of the OXTR gene affect people’s social interaction styles in various social encounters: carriers of the OXTR GG, compared to the OXTR AA/AG in general, are more motivated to interact socially and detect social salience. We focus on sales professionals operating in knowledge intensive organizations. Study 1, with a sample of 141 sales people, shows that carriers of the OXTR GG allele, compared to the OXTR AA/AG allele, are more motivated to help customers than to manipulatively impose goods/services on them. Study 2, using genomic functional magnetic resonance imaging (fMRI on a sample of 21 sales professionals processing facial pictures with different emotional valences, investigates key nuclei of social brain regions (SBRs. Compared to OXTR AA/AG carriers, OXTR GG carriers experience greater effective connectivity between SBRs of interest measured by Granger causality tests using univariate Haugh tests. In addition, the multivariate El-Himdi and Roy tests demonstrate that the amygdala, prefrontal cortex, and pars opercularis (inferior frontal gyrus play key roles when processing emotional expressions. The bilateral amygdala and medial prefrontal cortex show significantly greater clout – influence on other brain regions – for GG allele carriers than non-carriers; likewise, the bilateral pars opercularis, left amygdala, and left medial prefrontal cortex are more receptive to activity in other brain regions among GG allele carriers than AG/AA allele carriers are. Thus, carriers of the OXTR GG allele are more sensitive to changes in emotional cues, enhancing social salience. To our knowledge, this is the first study on how insights from imaging genetics help understanding of the social motivation of people operating in a professional setting.

Polymorphisms of the OXTR gene explain why sales professionals love to help customers.

Science.gov (United States)

Verbeke, Willem; Bagozzi, Richard P; van den Berg, Wouter E; Lemmens, Aurelie

2013-01-01

Polymorphisms of the OXTR gene affect people's social interaction styles in various social encounters: carriers of the OXTR GG, compared to the OXTR AA/AG in general, are more motivated to interact socially and detect social salience. We focus on sales professionals operating in knowledge intensive organizations. Study 1, with a sample of 141 sales people, shows that carriers of the OXTR GG allele, compared to the OXTR AA/AG allele, are more motivated to help customers than to manipulatively impose goods/services on them. Study 2, using genomic functional magnetic resonance imaging (fMRI) on a sample of 21 sales professionals processing facial pictures with different emotional valences, investigates key nuclei of social brain regions (SBRs). Compared to OXTR AA/AG carriers, OXTR GG carriers experience greater effective connectivity between SBRs of interest measured by Granger causality tests using univariate Haugh tests. In addition, the multivariate El-Himdi and Roy tests demonstrate that the amygdala, prefrontal cortex, and pars opercularis (inferior frontal gyrus) play key roles when processing emotional expressions. The bilateral amygdala and medial prefrontal cortex (mPFC) show significantly greater clout-influence on other brain regions-for GG allele carriers than non-carriers; likewise, the bilateral pars opercularis, left amygdala, and left mPFC are more receptive to activity in other brain regions among GG allele carriers than AG/AA allele carriers are. Thus, carriers of the OXTR GG allele are more sensitive to changes in emotional cues, enhancing social salience. To our knowledge, this is the first study on how insights from imaging genetics help understanding of the social motivation of people operating in a professional setting.

Polymorphisms of the OXTR gene explain why sales professionals love to help customers

Science.gov (United States)

Verbeke, Willem; Bagozzi, Richard P.; van den Berg, Wouter E.; Lemmens, Aurelie

2013-01-01

Polymorphisms of the OXTR gene affect people's social interaction styles in various social encounters: carriers of the OXTR GG, compared to the OXTR AA/AG in general, are more motivated to interact socially and detect social salience. We focus on sales professionals operating in knowledge intensive organizations. Study 1, with a sample of 141 sales people, shows that carriers of the OXTR GG allele, compared to the OXTR AA/AG allele, are more motivated to help customers than to manipulatively impose goods/services on them. Study 2, using genomic functional magnetic resonance imaging (fMRI) on a sample of 21 sales professionals processing facial pictures with different emotional valences, investigates key nuclei of social brain regions (SBRs). Compared to OXTR AA/AG carriers, OXTR GG carriers experience greater effective connectivity between SBRs of interest measured by Granger causality tests using univariate Haugh tests. In addition, the multivariate El-Himdi and Roy tests demonstrate that the amygdala, prefrontal cortex, and pars opercularis (inferior frontal gyrus) play key roles when processing emotional expressions. The bilateral amygdala and medial prefrontal cortex (mPFC) show significantly greater clout—influence on other brain regions—for GG allele carriers than non-carriers; likewise, the bilateral pars opercularis, left amygdala, and left mPFC are more receptive to activity in other brain regions among GG allele carriers than AG/AA allele carriers are. Thus, carriers of the OXTR GG allele are more sensitive to changes in emotional cues, enhancing social salience. To our knowledge, this is the first study on how insights from imaging genetics help understanding of the social motivation of people operating in a professional setting. PMID:24348351

Heightened amygdala responsiveness in s-carriers of 5-HTTLPR genetic polymorphism reflects enhanced cortical rather than subcortical inputs: An MEG study.

Science.gov (United States)

Luo, Qian; Holroyd, Tom; Mitchell, Derek; Yu, Henry; Cheng, Xi; Hodgkinson, Colin; Chen, Gang; McCaffrey, Daniel; Goldman, David; Blair, R James

2017-09-01

Short allele carriers (S-carriers) of the serotonin transporter gene (5-HTTLPR) show an elevated amygdala response to emotional stimuli relative to long allele carriers (LL-homozygous). However, whether this reflects increased responsiveness of the amygdala generally or interactions between the amygdala and the specific input systems remains unknown. It is argued that the amygdala receives input via a quick subcortical and a slower cortical pathway. If the elevated amygdala response in S-carriers reflects generally increased amygdala responding, then group differences in amygdala should be seen across the amygdala response time course. However, if the difference is a secondary consequence of enhanced amygdala-cortical interactions, then group differences might only be present later in the amygdala response. Using magnetoencephalography (MEG), we found an enhanced amygdala response to fearful expressions starting 40-50 ms poststimulus. However, group differences in the amygdala were only seen 190-200 ms poststimulus, preceded by increased superior temporal sulcus (STS) responses in S-carriers from 130 to 140 ms poststimulus. An enhanced amygdala response to angry expressions started 260-270 ms poststimulus with group differences in the amygdala starting at 160-170 ms poststimulus onset, preceded by increased STS responses in S-carriers from 150 to 160 ms poststimulus. These suggest that enhanced amygdala responses in S-carriers might reflect enhanced STS-amygdala connectivity in S-carriers. Hum Brain Mapp 38:4313-4321, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

DNA glycosylases involved in base excision repair may be associated with cancer risk in BRCA1 and BRCA2 mutation carriers

NARCIS (Netherlands)

Osorio, A.; Milne, R.L.; Kuchenbaecker, K.; Vaclova, T.; Pita, G.; Alonso, R.; Peterlongo, P.; Blanco, I.; Hoya, M. de la; Duran, M.; Diez, O.; Ramon, Y.C.T.; Konstantopoulou, I.; Martinez-Bouzas, C.; Conejero, R. Andres; Soucy, P.; McGuffog, L.; Barrowdale, D.; Lee, A.; Swe, B.; Arver, B.; Rantala, J.; Loman, N.; Ehrencrona, H.; Olopade, O.I.; Beattie, M.S.; Domchek, S.M.; Nathanson, K.; Rebbeck, T.R.; Arun, B.K.; Karlan, B.Y.; Walsh, C.; Lester, J.; John, E.M.; Whittemore, A.S.; Daly, M.B.; Southey, M.; Hopper, J.; Terry, M.B.; Buys, S.S.; Janavicius, R.; Dorfling, C.M.; Rensburg, E.J. van; Steele, L.; Neuhausen, S.L.; Ding, Y.C.; Hansen, T.V.; Jonson, L.; Ejlertsen, B.; Gerdes, A.M.; Infante, M.; Herraez, B.; Moreno, L.T.; Weitzel, J.N.; Herzog, J.; Weeman, K.; Manoukian, S.; Peissel, B.; Zaffaroni, D.; Scuvera, G.; Bonanni, B.; Mariette, F.; Volorio, S.; Viel, A.; Varesco, L.; Papi, L.; Ottini, L.; Tibiletti, M.G.; Radice, P.; Yannoukakos, D.; Garber, J.; Ellis, S.; Frost, D.; Platte, R.; Fineberg, E.; Evans, G.; Lalloo, F.; Izatt, L.; Eeles, R.; Adlard, J.; Davidson, R.; Cole, T.; Eccles, D.; Cook, J; Hodgson, S.; Brewer, C.; Tischkowitz, M.; Douglas, F.; Porteous, M.; Side, L.; Walker, L.; Morrison, P.; Donaldson, A.; Kennedy, J.; Foo, C.; Godwin, A.K.; Schmutzler, R.K.; Wappenschmidt, B.; Rhiem, K.; Engel, C.; Hoogerbrugge-van der Linden, N.; et al.,

2014-01-01

Single Nucleotide Polymorphisms (SNPs) in genes involved in the DNA Base Excision Repair (BER) pathway could be associated with cancer risk in carriers of mutations in the high-penetrance susceptibility genes BRCA1 and BRCA2, given the relation of synthetic lethality that exists between one of the

Effect of Bcl-2 rs956572 polymorphism on age-related gray matter volume changes.

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Mu-En Liu

Full Text Available The anti-apoptotic protein B-cell CLL/lymphoma 2 (Bcl-2 gene is a major regulator of neural plasticity and cellular resilience. Recently, the Bcl-2 rs956572 single nucleotide polymorphism was proposed to be a functional allelic variant that modulates cellular vulnerability to apoptosis. Our cross-sectional study investigated the genetic effect of this Bcl-2 polymorphism on age-related decreases in gray matter (GM volume across the adult lifespan. Our sample comprised 330 healthy volunteers (191 male, 139 female with a mean age of 56.2±22.0 years (range: 21-92. Magnetic resonance imaging and genotyping of the Bcl-2 rs956572 were performed for each participant. The differences in regional GM volumes between G homozygotes and A-allele carriers were tested using optimized voxel-based morphometry. The association between the Bcl-2 rs956572 polymorphism and age was a predictor of regional GM volumes in the right cerebellum, bilateral lingual gyrus, right middle temporal gyrus, and right parahippocampal gyrus. We found that the volume of these five regions decreased with increasing age (all P<.001. Moreover, the downward slope was steeper among the Bcl-2 rs956572 A-allele carriers than in the G-homozygous participants. Our data provide convergent evidence for the genetic effect of the Bcl-2 functional allelic variant in brain aging. The rs956572 G-allele, which is associated with significantly higher Bcl-2 protein expression and diminished cellular sensitivity to stress-induced apoptosis, conferred a protective effect against age-related changes in brain GM volume, particularly in the cerebellum.

Polymorphisms in tumor necrosis factor genes and susceptibility to visceral leishmaniasis in Moroccan children

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Rajaa Ejghal

2015-05-01

Full Text Available Objective: To examine whether polymorphic alleles at these two loci are involved in the susceptibility to visceral leishmaniasis (VL in Moroccan children. Methods: We have genotyped polymorphisms by PCR-restricted fragment length polymorphisms in 102 patients with VL, 92 asymptomatic carriers [positive skin test delayedtype hypersensitivity (DTH+] and 40 healthy controls (negative skin test delayed-type hypersensitivity, with no history of Leishmania infection. Results: Regression analysis showed no significant association between polymorphisms of tumor necrosis factors-ααwhen comparing VL and DTH + group (P > 0.05. The associations were detected between VL and negative skin test delayed-type hypersensitivity for the heterozygote genotype (P = 0.021, the recessive model: 1/2 + 2/2 (P = 0.044 and the minor allele 2 (P = 0.019. The resistance to VL was found to be under the recessive model 1/2 + 2/2 of tumor necrosis factors-β, when comparing VL and DTH + group (odds ratios: 0.558, 95%; confidence interval: 0.316-0.987; P = 0.044. Conclusions: These results must be regarded to preliminary but suggestive that further study with larger populations is worthwhile.

Association of STAT4 and PTPN22 polymorphisms and their interactions with type-1 autoimmune hepatitis susceptibility in Chinese Han children

OpenAIRE

Li, Xiaofeng; Chen, Huiqin; Cai, Yun; Zhang, Pingping; Chen, Zhuanggui

2017-01-01

Aims To investigate the impact of signal transducer and activator of transcription 4 (STAT4) and the protein tyrosine phosphatase N22 (PTPN22) gene single nucleotide polymorphisms (SNPs), gene–gene interactions and haplotype on type-1 Autoimmune Hepatitis (AIH) risk. Results Logistic regression analysis showed that type 1 AIH was significantly higher in carriers of T allele of rs7574865 than those with GG genotype (P- value less than 0.001), higher in carriers of C allele of rs7582694 than th...

Tuning crystal polymorphs of a Π-extended tetrathiafulvalene-based cruciform molecule towards high-performance organic field-effect transistors

DEFF Research Database (Denmark)

Feng, Linlin; Dong, Huanli; Li, Qingyuan

2017-01-01

It is a common phenomenon for organic semiconductors to crystallize in two or more polymorphs, leading to various molecular packings and different charge transport properties. Therefore, it is a crucial issue of tuning molecular crystal polymorphs (i.e., adjusting the same molecule with different......)-based cruciform molecule, named as IF-TTF. The charge carrier mobility of the α-phase IF-TTF crystals was more than one order of magnitude higher than that of β-phase crystals, suggesting the importance of reasonably tuning molecular packing in solid state for the improvement of charge transport in organic...... semiconductors...

Differential effect of beetroot bread on postprandial DBP according to Glu298Asp polymorphism in the eNOS gene: a pilot study.

Science.gov (United States)

Hobbs, D A; George, T W; Lovegrove, J A

2014-12-01

Our objective was to investigate whether the presence of Glu298Asp polymorphism in the endothelial NO synthase (eNOS) gene differentially affects the postprandial blood pressure response to dietary nitrate-rich beetroot bread. A randomised, single-blind, controlled, crossover acute pilot study was performed in 14 healthy men (mean age: 34±9 years) who were retrospectively genotyped for Glu298Asp polymorphism (7GG; T carriers 7). Volunteers were randomised to receive 200 g beetroot-enriched bread (1.1 mmol nitrate) or control bread (no beetroot; 0.01 mmol nitrate) on two separate occasions 10 days apart. Baseline and incremental area under the curve of blood pressure and NOx (nitrate/nitrite) were measured for a 6-h postprandial period. A treatment × genotype interaction was observed for diastolic blood pressure (Pconsumption of beetroot bread compared with control bread. No significant differences were observed in the GG group. The beneficial diastolic blood pressure reduction was observed only in the T carriers of the Glu298Asp polymorphism in the eNOS gene after consumption of nitrate-rich beetroot bread. These data require confirmation in a larger population group.

Associations of Cholesteryl Ester Transfer Protein TaqIB Polymorphism with the Composite Ischemic Cardiovascular Disease Risk and HDL-C Concentrations: A Meta-Analysis

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Shu-xia Guo

2016-09-01

Full Text Available Background: Previous studies have evaluated the associations between the cholesteryl ester transfer protein (CETP TaqIB polymorphism (rs708272, the risk of developing composite ischemic cardiovascular disease (CVD and the concentration of high-density lipoprotein cholesterol (HDL-C, but results remain controversial. The objective of this study was to investigate whether a relationship exists between these factors. Methods: We conducted a meta-analysis of available studies to clarify the associations of the CETP TaqIB polymorphism with HDL-C concentration and the composite ischemic CVD risk in both Asians and Caucasians. All statistical analyses were done with Stata 12.0. Results: Through utilization of the Cochrane Library, Embase, PubMed, Web of Science, Springer, China Science and Technology Journal Database, China National Knowledge Infrastructure, Google Scholar, and Baidu Library, a total of 45 studies from 44 papers with 20,866 cases and 21,298 controls were combined showing a significant association between the CETP TaqIB variant and composite ischemic CVD risk. Carriers of allele TaqIB-B1 were found to have a higher risk of composite ischemic CVD than non-carriers: OR = 1.15, 95% CI = 1.09–1.21, p < 0.001. Meanwhile, 28 studies with 23,959 subjects were included in the association between the CETP TaqIB polymorphism and the concentration of HDL-C. Results suggested that carriers of the B1B1 genotype had lower concentrations of HDL-C than those of the B2B2 genotype: SMD = 0.50, 95% CI = 0.36–0.65, p < 0.001. Conclusions: The synthesis of available evidence demonstrates that the CETP TaqIB polymorphism protects against composite ischemic CVD risk and is associated with a higher HDL-C concentration in both Asians and Caucasians.

Polymorphisms in the vitamin D receptor gene are associated with muscle strength in men and women.

Science.gov (United States)

Windelinckx, A; De Mars, G; Beunen, G; Aerssens, J; Delecluse, C; Lefevre, J; Thomis, M A I

2007-09-01

Vitamin D receptor (VDR) polymorphisms have been associated with fracture risk and muscle strength, although evidence for the latter is limited and conflicting. BsmI, TaqI and FokI VDR polymorphisms were genotyped in 253 men (54.9 +/- 10.2 yr) and 240 women (41.5 +/- 13.2 yr). Haplotypes were constructed for BsmI and TaqI. Handgrip, isometric (at 60 degrees , 120 degrees and 180 degrees joint angle) and eccentric torques (60 degrees /s) of knee extension and flexion were analysed using AN(C)OVA. Torque-velocity curves were constructed for concentric torques at 60 degrees /s, 180 degrees /s and 240 degrees /s and analysed using multivariate AN(C)OVA. Age, height and fat-free mass were included as covariates. Quadriceps isometric and concentric strength were higher in female f/f homozygotes compared to F allele carriers. Adjustment for confounding factors rendered results for quadriceps isometric strength at 120 degrees non-significant. No significant association was found with BsmI-TaqI haplotype in women. In contrast, male Bt/Bt homozygotes had higher isometric quadriceps strength at 150 degrees and higher concentric quadriceps strength than bT allele carriers without and with adjustment for confounding factors. No association was observed with FokI in men. In both genders, no interaction effect was present between BsmI-TaqI haplotype and FokI. Different VDR gene polymorphisms are associated with quadriceps strength in men and women.

Leu7Pro polymorphism of PreproNPY associated with an increased risk for type II diabetes in middle-aged subjects.

Science.gov (United States)

Ukkola, O; Kesäniemi, Y A

2007-09-01

Neuropeptide Y (NPY) plays a central in energy homeostasis and potentially in the development of obesity-related comorbidities, like type II diabetes. As the PreproNPY Leu7Pro polymorphism probably changes the intracellular processing of the synthesized preproNPY peptide, we assessed the hypothesis that PreproNPY Leu7Pro polymorphism is a risk factor for type II diabetes, impaired glucose tolerance and hypertension. Blood pressure recordings and oral glucose tolerance test were performed in the hypertensive (n=515) and control cohorts (n=525) of our well-defined Oulu Project Elucidating Risk of Atherosclerosis (OPERA) study. The prevalence of type II diabetes was 9% (n=93). The genotypes, insulin and glucose metabolism indexes and plasma ghrelin of the subjects were determined. Pro7 allele frequencies were 5.9, 5.3 and 11.3% in the total cohort, in subjects without and with type II diabetes, respectively. The PreproNPY Pro7 carrier status was a significant risk factor for type II diabetes, and the effect remained significant after adjustment for age, sex, waist circumference and study group (odds ratio=3.02, confidence interval: 1.67-5.44 and Pghrelin levels compared to non-carriers. The PreproNPY Pro7 allele is associated with an increased risk for type II diabetes. The risk seems to be associated with a higher insulin resistance among Pro7 carriers whereas low ghrelin concentrations in Pro7 carriers are possibly a consequence of high insulin levels.

Significant Association of Interleukin-10 Polymorphisms with Childhood Leukemia Susceptibility in Taiwan.

Science.gov (United States)

Lo, Wen-Jyi; Chang, Wen-Shin; Hsu, Han-Fang; Ji, Hong-Xue; Hsiao, Chieh-Lun; Tsai, Chia-Wen; Yeh, Su-Peng; Chen, Chuan-Mu; Bau, DA-Tian

2016-01-01

Mounting evidence supports the notion that inflammatory processes play a role in carcinogenesis, and interleukin-10 (IL10) is an important inflammatory cytokine. This study aimed to evaluate the contribution of IL10 A-1082G (rs1800896), T-819C (rs3021097) and A-592C (rs1800872) genotypes to the risk of childhood acute lymphoblastic leukemia (ALL) in Taiwan. Associations of these IL10 polymorphic genotypes with ALL risk were analyzed in 266 patients with childhood ALL patients and 266 non-cancer healthy controls by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) methodology. The results showed that CC genotype carriers at IL10 T-819C were at lower risk for childhood ALL (odds ratio=0.33, 95% confidence interval=0.16-0.68). On the contrary, AC and CC genotype carriers at IL10 A-592C were at higher risk for childhood ALL (odds ratio=1.73 and 6.34, 95% confidence interval=1.19-2.51 and 3.16-12.72, respectively). There was no difference in the distribution of A-1082G genotypes between childhood ALL and control groups. The genotypes at IL10 T-819C and A-592C may serve as predictive biomarkers for childhood ALL in Taiwan. Copyright © 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

Influence of the A3669G Glucocorticoid Receptor Gene Polymorphism on the Metabolic Profile of Pediatric Patients with Congenital Adrenal Hyperplasia

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Ricardo P. P. Moreira

2014-01-01

Full Text Available Background. Pediatric CAH patients have an increased risk of cardiovascular disease, and it remains unknown if genetic predisposition is a contributing factor. Glucocorticoid receptor gene (NR3C1 polymorphisms are associated with an adverse metabolic profile. Our aim was to analyze the association between the NR3C1 polymorphisms and the metabolic profile of pediatric CAH patients. Methods. Forty-one patients (26SW/15SV received glucocorticoid (GC replacement therapy to achieve normal androgen levels. Obesity was defined by BMI≥95th percentile. NR3C1 alleles were genotyped, and association analyses with phenotype were done with Chi-square, t-test, and multivariate and regression analysis. Results. Obesity was observed in 31.7% of patients and was not correlated with GC doses and treatment duration. Z-score BMI was positively correlated with blood pressure, triglycerides, LDL-c levels, and HOMA-IR. NR3C1 polymorphisms, BclI and A3669G, were found in 23.1% and 9.7% of alleles, respectively. A3669G carriers presented higher LDL-c levels compared to wild-type subjects. BclI-carriers and noncarriers did not differ. Conclusion. Our results suggest that A3669G-polymorphism could be involved with a susceptibility to adverse lipid profile in pediatric CAH patients. This study provides new insight into the GR screening during CAH treatment, which could help to identify the subgroup of at-risk patients who would most benefit from preventive therapeutic action.

CHRNA5 polymorphism and susceptibility to lung cancer in a Chinese population

Energy Technology Data Exchange (ETDEWEB)

Shen, Bo [Jiangsu Cancer Hospital, Department of Medical Oncology, Nanjing, Jiangsu Province (China); Zhu, Qun [Second Affiliated Hospital, Nanjing Medical University, Department of Endocrinology, Nanjing, Jiangsu Province (China); Zheng, Ma-Qing [College of Pharmacy, Nanjing University of Technology, Nanjing, Jiangsu Province (China); Chen, Jia; Shi, Mei-Qi; Feng, Ji-Feng [Jiangsu Cancer Hospital, Department of Medical Oncology, Nanjing, Jiangsu Province (China)

2013-01-11

Polymorphisms in the nicotinic acetylcholine receptor subunit CHRNA5 gene have been associated with lung cancer positive susceptibility in European and American populations. In the present hospital-based, case-control study, we determined whether polymorphism in rs503464 of CHRNA5 is associated with lung cancer risk in Chinese individuals. A single nucleotide polymorphism in CHRNA5 rs503464, c.-166T>A (hereafter T>A), was identified using TaqMan-MGB probes with sequencing via PCR in 600 lung cancer cases and 600 healthy individuals. Genotype frequencies for rs503464 (T>A) were in Hardy-Weinberg equilibrium for the control population. However, genotype frequencies were significantly different between cases and controls (P < 0.05), while allele frequencies were not significantly different between groups. Compared to homozygous genotypes (TT or AA), the risk of lung cancer in those with the heterozygous genotype (TA) was significantly lower (OR = 0.611, 95%CI = 0.486-0.768, P = 0.001). Using genotype AA as a reference, the risk of lung cancer for those with genotype TA was increased 1.5 times (OR = 1.496, 95%CI = 1.120-1.997, P = 0.006). However, no difference in risk was observed between T allele carriers and A allele carriers (OR = 0.914, 95%CI = 0.779-1.073, P = 0.270). Stratification analysis showed that the protective effect of TA was more pronounced in those younger than 60 years, nonsmokers, or those without a family history of cancer, as well as in patients with adenocarcinoma or squamous cell carcinoma in clinical stages III or IV (P < 0.05). Therefore, the heterozygous genotype c.-166T>A at rs503464 of CHRNA5 may be associated with reduced risk of lung cancer, thus representing a susceptibility allele in Chinese individuals.

CHRNA5 polymorphism and susceptibility to lung cancer in a Chinese population

International Nuclear Information System (INIS)

Shen, Bo; Zhu, Qun; Zheng, Ma-Qing; Chen, Jia; Shi, Mei-Qi; Feng, Ji-Feng

2013-01-01

Polymorphisms in the nicotinic acetylcholine receptor subunit CHRNA5 gene have been associated with lung cancer positive susceptibility in European and American populations. In the present hospital-based, case-control study, we determined whether polymorphism in rs503464 of CHRNA5 is associated with lung cancer risk in Chinese individuals. A single nucleotide polymorphism in CHRNA5 rs503464, c.-166T>A (hereafter T>A), was identified using TaqMan-MGB probes with sequencing via PCR in 600 lung cancer cases and 600 healthy individuals. Genotype frequencies for rs503464 (T>A) were in Hardy-Weinberg equilibrium for the control population. However, genotype frequencies were significantly different between cases and controls (P < 0.05), while allele frequencies were not significantly different between groups. Compared to homozygous genotypes (TT or AA), the risk of lung cancer in those with the heterozygous genotype (TA) was significantly lower (OR = 0.611, 95%CI = 0.486-0.768, P = 0.001). Using genotype AA as a reference, the risk of lung cancer for those with genotype TA was increased 1.5 times (OR = 1.496, 95%CI = 1.120-1.997, P = 0.006). However, no difference in risk was observed between T allele carriers and A allele carriers (OR = 0.914, 95%CI = 0.779-1.073, P = 0.270). Stratification analysis showed that the protective effect of TA was more pronounced in those younger than 60 years, nonsmokers, or those without a family history of cancer, as well as in patients with adenocarcinoma or squamous cell carcinoma in clinical stages III or IV (P < 0.05). Therefore, the heterozygous genotype c.-166T>A at rs503464 of CHRNA5 may be associated with reduced risk of lung cancer, thus representing a susceptibility allele in Chinese individuals

Preproghrelin Leu72Met polymorphism in Chinese subjects with coronary artery disease and controls.

Science.gov (United States)

Tang, Na-Ping; Wang, Lian-Sheng; Yang, Li; Gu, Hai-Juan; Zhu, Huai-Jun; Zhou, Bo; Sun, Qing-Min; Cong, Ri-Hong; Wang, Bin

2008-01-01

Ghrelin, a novel endogenous ligand for the growth hormone secretagogue receptor, is considered to exert a protective effect against atherosclerosis. The Leu72Met (+408C>A) polymorphic variant of the preproghrelin, the gene for the ghrelin precursor, has been linked to obesity, diabetes and metabolic syndrome. However, it is unclear whether this polymorphism is associated with coronary artery disease (CAD). We conducted a case-control study with 317 CAD patients and 323 controls to investigate the potential association of the Leu72Met polymorphism with the occurrence of CAD and CAD-related phenotypes in Chinese population. No significant difference in the Leu72Met genotype frequency was observed between CAD patients and controls (P=NS). The Leu72Met polymorphism was not associated with hypertension, diabetes, dyslipidemia, the number of diseased vessels, plasma total cholesterol, triglyceride, high density lipoprotein cholesterol, low density lipoprotein cholesterol or fasting glucose levels in CAD patients. However, among CAD patients, those with variant genotypes (Leu72Met and Met72Met) had lower BMI (24.4+/-0.3 kg/m(2)) than Leu72Leu carriers (25.4+/-0.2 kg/m(2), adjusted P=0.033). Our data indicate that the preproghrelin Leu72Met polymorphism is not associated with CAD in Chinese population. However, the Leu72Met variant is associated with BMI among CAD patients.

Interaction between BDNF Polymorphism and Physical Activity on Inhibitory Performance in the Elderly without Cognitive Impairment

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Anne Canivet

2017-11-01

Full Text Available Background: In the elderly, physical activity (PA enhances cognitive performances, increases brain plasticity and improves brain health. The neurotrophic hypothesis is that the release of brain-derived neurotrophic factor (BDNF, which is implicated in brain plasticity and cognition, is triggered by PA because motoneurons secrete BDNF into the bloodstream during exercise. Individual differences in cognitive performance may be explained by individual differences in genetic predisposition. A single nucleotide polymorphism on the BDNF gene, BDNFVal66Met, affects activity-dependent BDNF secretion. This study investigated the influence of the BDNFVal66Met polymorphism on the relationship between PA and controlled inhibition performance in older adults.Methods: A total of 114 healthy elderly volunteers (mean age = 71.53 years old were evaluated. Participants were genotyped for the BDNFVal66Met polymorphism. We evaluated inhibitory performance using choice reaction times (RT and error rates from a Simon-like task and estimated their PA using two self-reported questionnaires. We established four groups according to PA level (active vs. inactive and BDNFVal66Met genotype (Met carriers vs. Val-homozygous. The results were analyzed using ANOVA and ANCOVA, including age, gender and body mass index as covariates.Results: The BDNFVal66Met polymorphism interacted with PA on controlled inhibition performance. More specifically, inactive Val-homozygous participants exhibited a lower inhibition performance than active Val homozygotes and inactive Met carriers; the former had a higher error rate without differences in RT.Conclusion: Differences between individuals on inhibitory performance may be partially understood by the interaction between genetic influence in BDNF secretion and PA level. The results of this study clearly support the neurotrophic hypothesis that BDNF synthesis is an important mechanism underlying the influence of physical activity on brain

The peptidylglycine-α-amidating monooxygenase (PAM) gene rs13175330 A>G polymorphism is associated with hypertension in a Korean population.

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Yoo, Hye Jin; Kim, Minjoo; Kim, Minkyung; Chae, Jey Sook; Lee, Sang-Hyun; Lee, Jong Ho

2017-11-21

Peptidylglycine-α-amidating monooxygenase (PAM) may play a role in the secretion of atrial natriuretic peptide (ANP), which is a hormone involved in the maintenance of blood pressure (BP). The objective of the present study was to determine whether PAM is a novel candidate gene for hypertension (HTN). A total of 2153 Korean participants with normotension and HTN were included. Genotype data were obtained using the Korean Chip. The rs13175330 polymorphism of the PAM gene was selected from the ten single nucleotide polymorphisms (SNPs) most strongly associated with BP. The presence of the G allele of the PAM rs13175330 A>G SNP was associated with a higher risk of HTN after adjustments for age, sex, BMI, smoking, and drinking [OR 1.607 (95% CI 1.220-2.116), p = 0.001]. The rs13175330 G allele carriers in the HTN group treated without antihypertensive therapy (HTN w/o therapy) had significantly higher systolic and diastolic BP than the AA carriers, whereas the G allele carriers in the HTN group treated with antihypertensive therapy (HTN w/ therapy) showed significantly higher diastolic BP. Furthermore, rs13175330 G allele carriers in the HTN w/o therapy group had significantly increased levels of insulin, insulin resistance, and oxidized low-density lipoprotein (LDL) and significantly decreased LDL-cholesterol levels and LDL particle sizes compared to the AA carriers. These results suggest that the PAM rs13175330 A>G SNP is a novel candidate gene for HTN in the Korean population. Additionally, the PAM rs13175330 G allele might be associated with insulin resistance and LDL atherogenicity in patients with HTN.

Genetic effect of MTHFR C677T polymorphism on the structural covariance network and white-matter integrity in Alzheimer's disease.

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Chang, Yu-Tzu; Hsu, Shih-Wei; Tsai, Shih-Jen; Chang, Ya-Ting; Huang, Chi-Wei; Liu, Mu-En; Chen, Nai-Ching; Chang, Wen-Neng; Hsu, Jung-Lung; Lee, Chen-Chang; Chang, Chiung-Chih

2017-06-01

The 677 C to T transition in the MTHFR gene is a genetic determinant for hyperhomocysteinemia. We investigated whether this polymorphism modulates gray matter (GM) structural covariance networks independently of white-matter integrity in patients with Alzheimer's disease (AD). GM structural covariance networks were constructed by 3D T1-magnetic resonance imaging and seed-based analysis. The patients were divided into two genotype groups: C homozygotes (n = 73) and T carriers (n = 62). Using diffusion tensor imaging and white-matter parcellation, 11 fiber bundle integrities were compared between the two genotype groups. Cognitive test scores were the major outcome factors. The T carriers had higher homocysteine levels, lower posterior cingulate cortex GM volume, and more clusters in the dorsal medial lobe subsystem showing stronger covariance strength. Both posterior cingulate cortex seed and interconnected peak cluster volumes predicted cognitive test scores, especially in the T carriers. There were no between-group differences in fiber tract diffusion parameters. The MTHFR 677T polymorphism modulates posterior cingulate cortex-anchored structural covariance strength independently of white matter integrities. Hum Brain Mapp 38:3039-3051, 2017. © 2017 The Authors Human Brain Mapping Published Wiley by Periodicals, Inc. © 2017 The Authors Human Brain Mapping Published Wiley by Periodicals, Inc.

Common variants associated with breast cancer in genome-wide association studies are modifiers of breast cancer risk in BRCA1 and BRCA2 mutation carriers

NARCIS (Netherlands)

Wang, Xianshu; Pankratz, V. Shane; Fredericksen, Zachary; Tarrell, Robert; Karaus, Mary; McGuffog, Lesley; Pharaoh, Paul D. P.; Ponder, Bruce A. J.; Dunning, Alison M.; Peock, Susan; Cook, Margaret; Oliver, Clare; Frost, Debra; Sinilnikova, Olga M.; Stoppa-Lyonnet, Dominique; Mazoyer, Sylvie; Houdayer, Claude; Hogervorst, Frans B. L.; Hooning, Maartje J.; Ligtenberg, Marjolijn J.; Spurdle, Amanda; Chenevix-Trench, Georgia; Schmutzler, Rita K.; Wappenschmidt, Barbara; Engel, Christoph; Meindl, Alfons; Domchek, Susan M.; Nathanson, Katherine L.; Rebbeck, Timothy R.; Singer, Christian F.; Gschwantler-Kaulich, Daphne; Dressler, Catherina; Fink, Anneliese; Szabo, Csilla I.; Zikan, Michal; Foretova, Lenka; Claes, Kathleen; Thomas, Gilles; Hoover, Robert N.; Hunter, David J.; Chanock, Stephen J.; Easton, Douglas F.; Antoniou, Antonis C.; Couch, Fergus J.; Gregory, Helen; Miedzybrodzka, Zosia; Morrison, Patrick; Cole, Trevor; McKeown, Carole; Taylor, Amy; Donaldson, Alan; Paterson, Joan; Murray, Alexandra; Rogers, Mark; McCann, Emma; Kennedy, John; Barton, David; Porteous, Mary; Brewer, Carole; Kivuva, Emma; Searle, Anne; Goodman, Selina; Davidson, Rosemarie; Murday, Victoria; Bradshaw, Nicola; Snadden, Lesley; Longmuir, Mark; Watt, Catherine; Izatt, Louise; Pichert, Gabriella; Langman, Caroline; Dorkins, Huw; Barwell, Julian; Chu, Carol; Bishop, Tim; Miller, Julie; Ellis, Ian; Evans, D. Gareth; Lalloo, Fiona; Holt, Felicity; Male, Alison; Robinson, Anne; Gardiner, Carol; Douglas, Fiona; Claber, Oonagh; Walker, Lisa; McLeod, Diane; Eeles, Ros; Shanley, Susan; Rahman, Nazneen; Houlston, Richard; Bancroft, Elizabeth; D'Mello, Lucia; Page, Elizabeth; Ardern-Jones, Audrey; Mitra, Anita; Cook, Jackie; Quarrell, Oliver; Bardsley, Cathryn; Hodgson, Shirley; Goff, Sheila; Brice, Glen; Winchester, Lizzie; Eccles, Diana; Lucassen, Anneke; Crawford, Gillian; Tyler, Emma; McBride, Donna; Bérard, Léon; Sinilnikova, Olga; Barjhoux, Laure; Giraud, Sophie; Léone, Mélanie; Gauthier-Villars, Marion; Moncoutier, Virginie; Belotti, Muriel; de Pauw, Antoine; Bressac-de-Paillerets, Brigitte; Remenieras, Audrey; Byrde, Véronique; Caron, Olivier; Lenoir, Gilbert; Bignon, Yves-Jean; Uhrhammer, Nancy; Lasset, Christine; Bonadona, Valérie; Hardouin, Agnès; Berthet, Pascaline; Sobol, Hagay; Bourdon, Violaine; Eisinger, Françoise; Coulet, Florence; Colas, Chrystelle; Soubrier, Florent; Coupier, Isabelle; Payrat, Jean-Philippe; Fournier, Joëlle; Révillion, Françoise; Vennin, Philippe; Adenis, Claude; Rouleau, Etienne; Lidereau, Rosette; Demange, Liliane; Nogues, Catherine; Muller, Danièle; Fricker, Jean-Pierre; Longy, Michel; Sevenet, Nicolas; Toulas, Christine; Guimbaud, Rosine; Gladieff, Laurence; Feillel, Viviane; Leroux, Dominique; Dreyfus, Hélèn; Rebischung, Christine; Cassini, Cécile; Olivier-Faivre, Laurence; Prieur, Fabienne; Ferrer, Sandra Fert; Frénay, Marc; Vénat-Bouvet, Laurence; Lynch, Henry T.; Hogervorst, Frans; Vernhoef, Senno; Pijpe, Anouk; van 't Veer, Laura; van Leeuwen, Flora; Rookus, Matti; Collée, Margriet; van den Ouweland, Ans; Kriege, Mieke; Schutte, Mieke; Hooning, Maartje; Seynaeve, Caroline; van Asperen, Christi; Wijnen, Juul; Vreeswijk, Maaike; Tollenaar, Rob; Devilee, Peter; Ligtenberg, Marjolijn; Hoogerbrugge, Nicoline; Ausems, Margreet; van der Luijt, Rob; Aalfs, Cora; van Os, Theo; Gille, Hans; Waisfisz, Quinten; Meijers-Heijboer, Hanne; Gomez-Garcia, Encarna; van Roozendaal, Kees; Blok, Marinus; Oosterwijk, Jan; van der Hout, Annemieke; Mourits, Marian; Vasen, Hans; Szabo, Csilla; Pohlreich, Petr; Kleibl, Zdenek; Machackova, Eva; Lukesova, Miroslava; de Leeneer, Kim; Poppe, Bruce; de Paepe, Anne

2010-01-01

Recent studies have identified single nucleotide polymorphisms (SNPs) that significantly modify breast cancer risk in BRCA1 and BRCA2 mutation carriers. Since these risk modifiers were originally identified as genetic risk factors for breast cancer in genome-wide association studies (GWASs),

Is Increased Susceptibility to Balkan Endemic Nephropathy in Carriers of Common GSTA1 (*A/*B Polymorphism Linked with the Catalytic Role of GSTA1 in Ochratoxin A Biotransformation? Serbian Case Control Study and In Silico Analysis

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Zorica Reljic

2014-08-01

Full Text Available Although recent data suggest aristolochic acid as a putative cause of Balkan endemic nephropathy (BEN, evidence also exists in favor of ochratoxin A (OTA exposure as risk factor for the disease. The potential role of xenobiotic metabolizing enzymes, such as the glutathione transferases (GSTs, in OTA biotransformation is based on OTA glutathione adducts (OTHQ-SG and OTB-SG in blood and urine of BEN patients. We aimed to analyze the association between common GSTA1, GSTM1, GSTT1, and GSTP1 polymorphisms and BEN susceptibility, and thereafter performed an in silico simulation of particular GST enzymes potentially involved in OTA transformations. GSTA1, GSTM1, GSTT1 and GSTP1 genotypes were determined in 207 BEN patients and 138 non-BEN healthy individuals from endemic regions by polymerase chain reaction (PCR. Molecular modeling in silico was performed for GSTA1 protein. Among the GST polymorphisms tested, only GSTA1 was significantly associated with a higher risk of BEN. Namely, carriers of the GSTA1*B gene variant, associated with lower transcriptional activation, were at a 1.6-fold higher BEN risk than those carrying the homozygous GSTA1*A/*A genotype (OR = 1.6; p = 0.037. In in silico modeling, we found four structures, two OTB-SG and two OTHQ-SG, bound in a GSTA1 monomer. We found that GSTA1 polymorphism was associated with increased risk of BEN, and suggested, according to the in silico simulation, that GSTA1-1 might be involved in catalyzing the formation of OTHQ-SG and OTB-SG conjugates.

Application of Single Strand Conformational Polymorphism (PCR-SSCP) in Identification of Some Beta-Globin Gene Mutations in A Group of Egyptian Beta-Thalassemia Patients and Carriers

International Nuclear Information System (INIS)

Somaya, E.T.; Soliman, M.D

2010-01-01

The present study investigated whether the single-strand conformational polymorphism (SSCP) method could be employed to identify (rather than simply detect) four of the most common beta-globin gene mutations in the Egyptian population: IVS-I-110, IVS-I-6, the IVS-I-1, and Codon 39. Using DNA from 90 beta-thalassemia patients and carriers, by PCR the appropriate 238-bp region of the human beta-globin gene was amplified, the reaction products (Single-stranded DNA) were analyzed by none denaturing polyacrylamide gel electrophoresis, and the bands visualized by silver staining. Single-stranded DNA (ssDNA) fragments showed reproducible pattern of bands that were characteristic of the mutations present. With the use of control samples containing six of the 10 possible combinations of the four beta-globin gene mutations under study, we were able to predict the mutations present in 23 out of 90 (26.4%) of the patients studied. These predictions were confirmed independently by the amplification refractory mutation system (ARMS) method. It is concluded that this non-radioactive PCR-SSCP method can be used to reliably identify mutations in beta-thalassemia patients, provided that suitable controls are available. However, usefulness of this method for determining the genotype of beta-thalassaemic individuals is obviously limited by the great number of controls required. Moreover, the ability to detect mutations by SSCP is in general lower compared to other methods, ARMS, DGGE or DHPLC, which are reported to detect 49.5% to 73% of the mutations present. The SSCP method is nevertheless much easier to employ than other methods and is especially successful for beta-thalassemia carriers. This method would thus be particularly useful for an initial screening of target groups (prenatal diagnosis)

Association of PPARG Pro12Ala polymorphism with insulin sensitivity and body mass index in patients with polycystic ovary syndrome.

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Baldani, Dinka Pavicic; Skrgatic, Lana; Cerne, Jasmina Z; Ferk, Polonca; Simunic, Velimir; Gersak, Ksenija

2014-03-01

Insulin resistance is one of the key factors in the pathogenesis of polycystic ovary syndrome (PCOS). The peroxisome proliferator-activated receptor gamma (PPARG) plays a role in the regulation of insulin sensitivity. The aim of the present study was to establish a possible association of the PPARG Pro12Ala polymorphism with PCOS and its effect on family and personal history, as well as on the metabolic and endocrine parameters in PCOS patients. A total of 151 PCOS patients and 179 healthy women of reproductive age were enrolled. History, body mass index (BMI), waist-to-hip ratio and the presence of phenotypic hyperandrogenism were recorded. Hormonal, metabolic and biochemical profiles were assessed. A molecular analysis for the genetic polymorphism was performed. One third (29.8%) of the PCOS patients were found to be carriers of at least one variant of the Ala allele (X/Ala), while 70.2% carried two wild-type Pro alleles (Pro/Pro), with an equal distribution observed in the control group. The PCOS patients carrying the X/Ala alleles exhibited lower serum fasting insulin levels, homeostatic model assessment of insulin resistance (HOMA-IR) and BMI compared to Pro/Pro carriers. This finding was significant only in the lean PCOS group. The polymorphic genotype exerted no effect on history, hormonal and clinical hyperandrogenism, lipid status or C-reactive protein, leptin, adiponectin, resistin and ghrelin serum levels in women with PCOS. In conclusion, although the PPARG Pro12Ala polymorphism is not a major determinant of PCOS in the Croatian population, it may exert a positive effect on insulin sensitivity and BMI. As these associations were recorded exclusively in the lean group of patients with PCOS, this polymorphism potentially contributes to a protective role against hyperinsulinemia and obesity.

The association of eight potentially functional polymorphisms in five adrenergic receptor-encoding genes with myocardial infarction risk in Han Chinese.

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Xia, Kun; Ding, Rongjing; Zhang, Zhiyong; Li, Weiming; Shang, Xiaoming; Yang, Xinchun; Wang, Lefeng; Zhang, Qi

2017-08-15

Adrenergic receptors play a key role in activating the sympathetic nervous system, which often accompanies with the development of myocardial infarction (MI). Here, we aimed to test the association of eight potentially functional polymorphisms in five adrenergic receptor-encoding genes with MI risk. Genotypes were available for 717 MI patients and 612 controls. There were no detectable deviations from the Hardy-Weinberg equilibrium for all study polymorphisms. Allele frequencies differed remarkably for ADRA2B D/I (P<0.001), ADRB1 Ser49Gly (P=0.002), ADRB2 Gln27Glu (P=0.005), and ADRB3 Trp64Arg (P<0.001) polymorphisms, even after the Bonferroni correction. Systolic blood pressure was significantly lower in ADRA2B II genotype carriers than in the DD genotype carriers (P=0.006), while plasma high-density lipoprotein cholesterol was significantly higher in patients carrying ADRA2B I allele and ADRB1 49Ser allele than in patients with the DD genotype and 49Gly/49Gly genotype, respectively (P=0.018 and 0.033). Overall best interaction model consisted of ADRA2B D/I, ADRB1 Ser49Gly, dyslipidemia and hypertension, with the highest testing accuracy of 0.627 and the maximal 10-fold cross-validation consistency (P=0.017). Finally, a nomogram was depicted based on four significant polymorphisms and metabolic risk factors, and it had a better predictive utility and was internally validated with a discrimination C-index of 0.723 (P<0.001). Altogether, we identified two polymorphisms, ADRA2B D/I and ADRB1 Ser49Arg, which not only altered genetic susceptibility to MI, but also impacted on blood pressure and plasma lipid changes, and their combination with metabolic risk factors constituted the overall best interaction model. Copyright © 2017. Published by Elsevier B.V.

SCN1A, ABCC2 and UGT2B7 gene polymorphisms in association with individualized oxcarbazepine therapy.

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Ma, Chun-Lai; Wu, Xun-Yi; Jiao, Zheng; Hong, Zhen; Wu, Zhi-Yuan; Zhong, Ming-Kang

2015-01-01

Associations between the effects of SCN1A, SCN2A, ABCC2 and UGT2B7 genetic polymorphisms and oxcarbazepine (OXC) maintenance doses in Han Chinese epileptic patients were investigated. Genetic polymorphisms were detected in 184 epileptic patients receiving OXC monotherapy by high-resolution melting curve and TaqMan method. Carriers of the SCN1A IVS5-91G>A, UGT2B7 c.802T>C and ABCC2 c.1249G>A variant alleles required significantly higher OXC maintenance doses than noncarriers (p GA > AA. SCN1A, UGT2B7 and ABCC2 genetic polymorphisms are associated with OXC maintenance doses and may be useful for the personalization of OXC therapy in epileptic patients. Further studies are needed. Original submitted 6 June 2014; Revision submitted 5 September 2014.

Combined effect of genetic polymorphisms of AURKA and environmental factors on oral cancer development in Taiwan.

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Chia-Hsuan Chou

Full Text Available Oral squamous cell carcinoma (OSCC is the sixth and fourth most common cause of cancer death in men worldwide and in Taiwan, respectively. AURKA, which encodes a centrosome-related serine/threonine kinase, is frequently amplified and overexpressed in many human cancers, particularly advanced OSCC. We conducted a hospital-based case-control study to estimate AURKA single-nucleotide polymorphisms (SNPs and environmental risk factors to determine OSCC susceptibility and clinicopathological characteristics.We enrolled a total of 876 OSCC patients and 1200 controls. Four SNPs of AURKA, namely rs1047972, rs2273535, rs2064863, and rs6024836, were analyzed using real-time polymerase chain reaction (PCR. Among the 1420 smokers, the AURKA polymorphism carriers with the betel nut chewing habit had a higher risk of oral cancer than AURKA wild-type (WT carriers without the betel nut chewing habit. Patients with the AURKA rs2064863 gene had a 1.365-fold higher risk of stage III or IV OSCC (95% confidence interval [CI] 1.029-1.811 than those with the rs2064863 WT gene. Furthermore, carriers of the AURKA rs1047972/rs2273535/rs2064863 C-A-T haplotype had a 1.736-fold (95% CI 1.110-2.715 higher risk of OSCC than controls (C-T-T, the most common haplotype. Among patients with the betel quid chewing habit, carriers of other haplotypes (C-T-T, C-A-G, T-A-T, T-A-G, T-T-T, and C-T-G had a 12.857-fold (95% CI 10.731-15.404 increased risk, and carriers of the C-A-T haplotype had the highest risk (AOR: 31.120; 95% CI 13.864-69.850 of OSCC, compared with those without the betel quid chewing who harbored other haplotypes.In conclusion, betel nut chewing combined with the AURKA C-A-T haplotypes lead to a high risk of OSCC. These findings reveal a novel genetic-environmental predisposition for oral tumorigenesis.

Apolipoprotein E gene polymorphism and its effect on anthropometric measures in normoglycemic subjects and type 2 diabetes

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Tabatabaei-Malazy Ozra

2012-10-01

Full Text Available Abstract Background Apolipoprotein E (apo E plays a major role in lipid metabolism, obesity and accordingly in development of diabetes and coronary heart disease (CHD. Our main objective was to evaluate the association between apo E gene polymorphism with anthropometric measures. Methods Participants were selected from zone 17 Tehran/Iran. We assessed height, weight, body mass index (BMI, waist circumference (WC, blood pressure, serum fasting blood sugar, total cholesterol and triglycerides. Genotyping for apo E gene polymorphism was carried out using PCR-RFLP technique. Results Among total study population (n=311, 156 subjects were diabetic. The apo E3/E3 was the most common genotype in our population while E2 and E4 alleles had lower frequencies, respectively. After adjustment for diabetes, the apo E2 and E4 alleles were significantly associated with hypercholesterolemia and WC, respectively (p= 0.009, 0.034. This association was also related to sex and age. The probability of having abdominal obesity in E4 allele carriers was increased from 0.22 to 8.12 in women and to 3.08 in age ≥ 50 years. Conclusions Apo E polymorphism had significant influences on WC and total cholesterol level in patients with type 2 diabetes. This study highlights the importance of lifestyle modifications which may be more beneficial in hypercholesterolemic women carriers of E2 and E4 alleles concomitant central obesity.

Association of the plasminogen activator inhibitor-1 (PAI-1) Gene -675 4G/5G and -844 A/G promoter polymorphism with risk of keloid in a Chinese Han population.

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Wang, Yongjie; Long, Jianhong; Wang, Xiaoyan; Sun, Yang

2014-10-28

A keloid is pathological scar caused by aberrant response to skin injuries, characterized by excessive accumulation of histological extracellular matrix, and occurs in genetically susceptible individuals. Plasminogen activator inhibitor-1 (PAI-1) has been implicated in the pathogenesis of keloid. We investigated the association between PAI-1 polymorphisms and plasma PAI-1 level with keloid risk. A total of 242 Chinese keloid patients and 207 controls were enrolled in this study. Polymerase chain reaction-restriction technique was used to determine PAI-1 promoter polymorphism (-675 4G/5G and -844 A/G) distribution. Plasma PAI-1 levels were detected using enzyme-linked immunosorbent assay (ELISA). There was a statistically significant difference in the distribution of PAI-1 -675 4G/5G polymorphism between keloid patients and healthy controls. 4G/4G carriers were more likely to develop keloid. In contrast, the -844 A/G polymorphism distribution did not vary significantly between keloid patients and controls. The keloid patients group had a significantly higher plasma PAI-1 level than the control group. In the -675 4G/4G carrier population, the plasma PAI-1 levels were significant higher in keloid patients compared with controls. Our study provides evidence that PAI-1 promoter polymorphism -675 4G/5G and plasma PAI-1 level are associated with keloid risk. PAI-1 -675 4G/5G polymorphism may be an important hereditary factor responsible for keloid development in the Chinese Han population.

The influence of folate pathway polymorphisms on high-dose methotrexate-related toxicity and survival in children with non-Hodgkin malignant lymphoma

International Nuclear Information System (INIS)

Erculj, Nina; Kotnik, Barbara Faganel; Debeljak, Marusa; Jazbec, Janez; Dolzan, Vita

2014-01-01

We evaluated the influence of folate pathway polymorphisms on high-dose methotrexate (HD-MTX) related toxicity in paediatric patients with T-cell non-Hodgkin lymphoma (NHL). In total, 30 NHL patients were genotyped for selected folate pathway polymorphisms. Carriers of at least one MTHFR 677T allele had significantly higher MTX area under the time-concentration curve levels at third MTX cycle (P = 0.003). These patients were also at higher odds of leucopoenia (P = 0.006) or thrombocytopenia (P = 0.041) and had higher number of different HD-MTX-related toxicity (P = 0.035) compared to patients with wild-type genotype. Our results suggest an important role of MTHFR 677C>T polymorphism in the development of HD-MTX-related toxicity in children with NHL

ACTN3 R577X POLYMORPHISM AND NEUROMUSCULAR RESPONSE TO RESISTANCE TRAINING

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Paulo Gentil

2011-06-01

Full Text Available The R577X polymorphism at the ACTN3 gene has been associated with muscle strength, hypertrophy and athletic status. The X allele, which is associated with the absence of ACTN3 protein is supposed to impair performance of high force/velocity muscle contractions. The purpose of the present study was to investigate the association of the R577X polymorphism with the muscle response to resistance training in young men. One hundred forty one men performed two resistance training sessions per week for 11 weeks. Participants were tested for 1RM bench press, knee extensors peak torque, and knee extensors muscle thickness at baseline and after the training period. Genotyping was conducted using de DdeI restriction enzyme. Genotype distribution was 34.4% for RR, 47% for RX and 18.6% for the XX genotype. According to the results, the R577X polymorphism at the ACTN3 gene is not associated with baseline muscle strength or with the muscle strength response to resistance training. However, only carriers of the R allele showed increases in muscle thickness in response to training

A haplotype of polymorphisms in ASE-1, RAI and ERCC1 and the effects of tobacco smoking and alcohol consumption on risk of colorectal cancer: a Danish prospective case-cohort study

DEFF Research Database (Denmark)

Hansen, Rikke D; Sørensen, Mette; Tjønneland, Anne

2008-01-01

BACKGROUND: Single nucleotide polymorphisms (SNPs) are the most frequent type of genetic variation in the human genome, and are of interest for the study of susceptibility to and protection from diseases. The haplotype at chromosome 19q13.2-3 encompassing the three SNPs ASE-1 G-21A, RAI IVS1 A4364G...... and ERCC1 Asn118Asn have been associated with risk of breast cancer and lung cancer. Haplotype carriers are defined as the homozygous carriers of RAI IVS1 A4364GA, ERCC1 Asn118AsnT and ASE-1 G-21AG. We aimed to evaluate whether the three polymorphisms and the haplotype are associated to risk of colorectal...... of colorectal cancer were found. No statistically significant interactions between the genotypes and the lifestyle exposures smoking or alcohol consumption were observed. CONCLUSION: Our results suggest that the ASE-1 G-21A, RAI IVS1 A4364G and ERCC1 Asn118Asn polymorphisms and the previously identified...

The Gln223Arg polymorphism of the leptin receptor in Pima Indians: influence on energy expenditure, physical activity and lipid metabolism

DEFF Research Database (Denmark)

Stefan, N; Vozarova, B; Del Parigi, A

2002-01-01

Leptin regulates body weight by its receptor-mediated anorectic, thermogenic and antisteatotic effects. Recently, lower leptin binding to the soluble form of the leptin receptor (LEPR) was shown in carriers of the Arg223-encoding allele of the Gln223Arg polymorphism of the LEPR. To investigate wh...

Linguistic grammar learning and DRD2-TAQ-IA polymorphism.

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Wong, Patrick C M; Ettlinger, Marc; Zheng, Jing

2013-01-01

As research into the neurobiology of language has focused primarily on the systems level, fewer studies have examined the link between molecular genetics and normal variations in language functions. Because the ability to learn a language varies in adults and our genetic codes also vary, research linking the two provides a unique window into the molecular neurobiology of language. We consider a candidate association between the dopamine receptor D2 gene (DRD2) and linguistic grammar learning. DRD2-TAQ-IA polymorphism (rs1800497) is associated with dopamine receptor D2 distribution and dopamine impact in the human striatum, such that A1 allele carriers show reduction in D2 receptor binding relative to carriers who are homozygous for the A2 allele. The individual differences in grammatical rule learning that are particularly prevalent in adulthood are also associated with striatal function and its role in domain-general procedural memory. Therefore, we reasoned that procedurally-based grammar learning could be associated with DRD2-TAQ-IA polymorphism. Here, English-speaking adults learned artificial concatenative and analogical grammars, which have been respectively associated with procedural and declarative memory. Language learning capabilities were tested while learners' neural hemodynamic responses were simultaneously measured by fMRI. Behavioral learning and brain activation data were subsequently compared with the learners' DRD2 (rs1800497) genotype. Learners who were homozygous for the A2 allele were better at concatenative (but not analogical) grammar learning and had higher striatal responses relative to those who have at least one A1 allele. These results provide preliminary evidence for the neurogenetic basis of normal variations in linguistic grammar learning and its link to domain-general functions.

Association of Vitamin D receptor gene polymorphisms with metabolic syndrome and its components among adult Arabs from the United Arab Emirates.

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Hasan, Hayder A; AbuOdeh, Ra'ed O; Muda, Wan Abdul Manan Bin Wan; Mohamed, Hamid Jan Bin Jan; Samsudin, Ab Rani

2017-12-01

The aim was to investigate relationships of Vitamin D receptor gene (VDR) polymorphisms to the components of MetS among Arabs adult residing in the United Arab Emirates. A cross-sectional study of 198 Arabs adult (50 males and 148 females). Serum levels of glucose, vitamin D, HDL-C, and TG, and blood pressure were measured. FokI, BsmI & TaqI genotyping of VDR were investigated using PCR-RFLP technique. Age of the participants was 21(9) years with a BMI of 26.8(7.8) kg/m 2 . About 15% had MetS with serum vitamin D levels of 25.5(18.2) nmol/L. VDR genotyping yielded: FokI: 57.1% FF and 38.9% Ff, BsmI: 29.8% bb and 51.5% Bb, while TaqI showed 39.4% TT and 43.4% Tt. The ff carriers had higher total cholesterol [174(12.4) mg/dl] than FF and Ff genotypes. Bb carriers showed higher BMI and LDL-C than BB and bb genotypes. In females, FokI VDR polymorphism showed significant association with systolic blood pressure (SBP) and F allele carriers were at higher risk of developing high SBP [x 2 =4.4, df1, OR=0.29 (95%CI: 0.087-0.98), p=0.035]. VDR gene polymorphisms were not associated with MetS, yet it may affect the severity of some of components of MetS, namely the association of BsmI with obesity, FokI and BsmI with dyslipidemia and FokI with SBP. Copyright © 2017 Diabetes India. Published by Elsevier Ltd. All rights reserved.

Pathogenetic significance of single nucleotide polymorphisms in the gastric inhibitory polypeptide receptor gene for the development of carbohydrate metabolism disorders in obesity

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Daria S. Skuratovskaia

2016-12-01

Conclusion. Serum insulin and C-peptide levels were increased in patients with abdominal obesity who were carriers of the CA genotype in the rs2302382 polymorphism of GIPR, which is associated with a decreased risk of type 2 diabetes mellitus in obesity compared with the CC genotype.

Association between the -455T>C promoter polymorphism of the APOC3 gene and the metabolic syndrome in a multi-ethnic sample

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Pollex, Rebecca L; Ban, Matthew R; Young, T Kue

2007-01-01

it also a potential genetic determinant for MetS. The objective of this study is to examine the APOC3 -455T>C and the INSIG2 rs7566605 polymorphisms as potential genetic determinants for MetS in a multi-ethnic sample. METHODS: Subjects were genotyped for both the APOC3 -455T>C and INSIG2 rs7566605...... definition). Carriers of > or =1 copy of APOC3 -455C were more likely to have MetS (NCEP ATP III definition) than noncarriers (carrier odds ratio 1.73, 95% CI 1.40 to 2.14, adjusting for age and study group). The basis of the association was related not only to a higher proportion of -455C carriers meeting...

Genetic polymorphisms of the CYP1A1, GSTM1, and GSTT1 enzymes and their influence on cardiovascular risk and lipid profile in people who live near a natural gas plant.

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Pašalić, Daria; Marinković, Natalija

2017-03-01

The aim of this cross-sectional study was to see whether genetic polymorphisms of the enzymes CYP1A1, GSTM1, and GSTT1 are associated with higher risk of coronary artery disease (CAD) and whether they affect lipid profile in 252 subjects living near a natural gas plant, who are likely to be exposed to polycyclic aromatic hydrocarbons (PAHs). Fasting serum concentrations of biochemical parameters were determined with standard methods. Genetic polymorphisms of CYP 1A1 rs4646903, rs1048943, rs4986883, and rs1799814 were genotyped with polymerase chain reaction-restriction fragment length polymorphism (PCR-RFPL), while GSTM1 and GSTT1 deletions were detected with multiplex PCR. Cardiovascular risk was assessed with Framingham risk score, and the subjects divided in two groups: >10% risk and ≤10% risk. The two groups did not differ in the genotype frequencies. MANCOVA analysis, which included lipid parameters, glucose, and BMI with sex, age, hypertension and smoking status as covariates, showed a significant difference between the GSTT1*0 and GSTT1*1 allele carriers (p=0.001). UNIANCOVA with same covariates showed that total cholesterol and triglyceride levels were significantly higher in GSTT1*1 allele carriers than in GSTT1*0 carriers (prisk of CAD, but that GSTT1 affects lipid profile.

Influence of prostate stem cell antigen gene polymorphisms on susceptibility to Helicobacter pylori-associated diseases: a case-control study.

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Ichikawa, Hitomi; Sugimoto, Mitsushige; Uotani, Takahiro; Sahara, Shu; Yamade, Mihoko; Iwaizumi, Moriya; Yamada, Takanori; Osawa, Satoshi; Sugimoto, Ken; Miyajima, Hiroaki; Yamaoka, Yoshio; Furuta, Takahisa

2015-04-01

Patients with duodenal ulcer have a reduced risk of developing gastric cancer compared to those without. Recently, the prostate stem cell antigen (PSCA) rs2294008 C>T polymorphism was found to be associated with different pathogenesis of duodenal ulcer and gastric cancer developments. However, whether PSCA rs2294008 C>T polymorphism is associated with severity of gastric mucosal atrophy is unclear. We examined the influence of the PSCA rs2294008 C>T polymorphism on susceptibility to H. pylori-related diseases and the relationships between PSCA polymorphism and gastric mucosal atrophy. PSCA rs2294008 C>T polymorphism was assessed in H. pylori-positive Japanese patients (n = 488) with noncardia gastric cancer (n = 193), gastric ulcer (n = 84), duodenal ulcer (n = 61), and atrophic gastritis (n = 150), as well as in H. pylori-negatives (n = 266). Frequency of PSCA rs2294008 C/C genotype in duodenal ulcer was 36.1%, which was significantly higher than those with gastric cancer (12.4%), gastric ulcer (19.0%), gastritis (10.7%), and H. pylori-negatives (19.5%) (p T polymorphism is associated with differing susceptibilities to H. pylori-associated diseases. The PSCA rs2294008 C>T polymorphism may be acting through induction of gastric mucosal atrophy, finally leading to development of gastric ulcer and gastric cancer in PSCA rs2294008 T allele carriers, but not duodenal ulcer. © 2014 John Wiley & Sons Ltd.

The serotonin transporter polymorphism (5-HTTLPR) and personality: response style as a new endophenotype for anxiety.

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Plieger, Thomas; Montag, Christian; Felten, Andrea; Reuter, Martin

2014-06-01

Although the serotonin transporter length polymorphic region (5-HTTLPR) polymorphism is an extensively-investigated genetic marker of anxiety related personality traits (neuroticism and harm avoidance) and affective disorders, effect sizes in meta-analyses are small, if present at all, and all available primary studies to date lack mandatory statistical power. Moreover, questionnaire data is prone to confounding by variables such as social desirability. Therefore, extreme response style (ERS) is suggested as a new approach to elucidate the relationship between 5-HTTLPR and negative emotionality, as it is more implicit and of high reliability. N = 1075 healthy subjects were genotyped for 5-HTTLPR and a flanking polymorphism (rs25531) and filled out the NEO Five Factor Inventory and the Temperament Character Inventory. As dependent variable the number of extreme responses across all items was calculated. Using the common genotype or the triallelic approach (including rs25531) the meta-analytic findings could not be replicated. However, there was a significant association between 5-HTTLPR and extreme response style. Carriers of the L-allele or the L'-allele, respectively, had a significantly higher number of extreme responses than homozygous SS carriers across all items of the NEO Five Factor Inventory. This finding could be replicated in an alternative personality questionnaire (Affective Neuroscience Personality Scales, ANPS). There is a long tradition in psychological assessment indicating that ERS is an implicit measure of personality. Given the positive findings of the present study, ERS qualifies as a promising endophenotype in future genetic association studies on personality and affective disorders.

A polymorphism in NFKB1 is associated with improved effect of interferon-alpha maintenance treatment of patients with multiple myeloma after high-dose treatment with stem cell support

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Vangsted, Annette J; Klausen, Tobias W; Gimsing, Peter

2009-01-01

and Methods: In a retrospective study of 296 patients with multiple myelom undergoing high-dose therapy between 1994 and 2004, 146 patients were treated with interferon- as maintenance therapy. We tested the polymorphisms IL1B T-31C, IL6 G-174C, NFKB1-94ins/delATTG, CD3EAP G-21A and PPP1R13L IVS1 A4364G...... homozygous for the wild type G allele of IL6 G-174C who survived longer (p= 0.0074) than variant allele carriers. There was no association between the polymorphisms IL1B T-31C, CD3EAP G-21A and PPP1R13L IVS1 A4364G and treatment outcome for interferon-. Conclusions: Patients who are homozygous carriers...

The impact of ACE gene polymorphism on the incidence and phenotype of sarcoidosis in rural and urban settings.

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Kieszko, Robert; Krawczyk, Paweł; Powrózek, Tomasz; Szudy-Szczyrek, Aneta; Szczyrek, Michał; Homa, Iwona; Daniluk, Jadwiga; Milanowski, Janusz

2016-12-01

Sarcoidosis is a multisystem granulomatous disease of unknown etiology. Current theory on the etiology of this disease involves participation of genetic factors and unknown antigens present in the patients' environment. The aim of the study was to evaluate the prevalence of different polymorphic forms of the ACE gene in healthy individuals and sarcoidosis patients, and to estimate the risk of sarcoidosis in carriers of different ACE genotypes living in rural and urban settings. The study group included 180 patients with pulmonary sarcoidosis. Assessment of the disease was based on clinical features, laboratory and imaging examinations, as well as bronchoscopy with bronchoalveolar lavage (BAL). ACE gene polymorphism was examined in DNA isolated from peripheral blood or BAL fluid (BALF) leukocytes. Incidence of sarcoidosis was not influenced by gender, age or place of residence of the patients. There were no differences in the frequency of particular genotypes in patients with sarcoidosis and in healthy individuals. The risk of disease did not depend on the ACE gene polymorphism. There were no differences in the frequencies of the different genotypes and alleles of the ACE gene in patients with sarcoidosis divided by gender, age and place of residence or by clinical manifestation of sarcoidosis. Our results do not support the previous concept which suggested a higher incidence of sarcoidosis in individuals living in rural areas and in carriers of selected ACE genotypes. It is possible that this is related to the changing environment of rural areas, increasing urbanization and pollution.

Brain-derived neurotrophic factor (BDNF) Val66Met polymorphism and post-stroke dementia: a hospital-based study from northern Iran.

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Rezaei, Sajjad; Asgari Mobarake, Karim; Saberi, Alia; Keshavarz, Parvaneh; Leili, Ehsan Kazemnejad

2016-06-01

Brain-derived neurotrophic factor (BDNF) Val66Met polymorphism is associated with functional and cognitive outcomes of stroke and plays a key role in preventing neuronal death. This study aimed to answer the following question: does BDNF Val66Met polymorphism prognosticate survival status and risk of post-stroke dementia (PSD)? In a retrospective cohort study, 206 patients with ischemic stroke (IS) entered the study. They were consecutively being admitted to the neurology clinic in Poursina Hospital (northern Iran) from 2012 to 2014. The diagnosis of PSD was based on DSM-5 criteria. The current and the premorbid cognitive statuses of the patients were respectively assessed through the third edition of Addenbrooke's Cognitive Examination and the Informant Questionnaire on Cognitive Decline in the Elderly. BDNF Val66Met gene polymorphism was determined by PCR-RFLP. On average, 48 patients (23.3 %) developed PSD 6 months after IS. Log-rank test showed that the survival rate of at least one Val-allele carriers was significantly lower than that of Met/Met homozygotes (P = 0.0005), and the former developed PSD sooner than the latter (375, 492 days, respectively). Cox model showed that heterozygous carriers of Val/Met were at greater risk of PSD over time (HR 2.280, 95 % CI 1.566-4.106, P = 0.006). However, the risk ratio of patients with PSD among different BDNF genotypes decreased after adjusting demographic, clinical, and vascular risk factors, and was no longer statistically significant (AHR 2.434, 95 % CI 0.597-9.926, P = 0.215). Val-allele carriers or Val/Met genotypes were more quickly diagnosed as having dementia after IS. However, this genetic vulnerability became more destructive when it was added to demographic, clinical, and vascular risk factors.

Eccentric muscle challenge shows osteopontin polymorphism modulation of muscle damage.

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Barfield, Whitney L; Uaesoontrachoon, Kitipong; Wu, Chung-Sheih; Lin, Stephen; Chen, Yue; Wang, Paul C; Kanaan, Yasmine; Bond, Vernon; Hoffman, Eric P

2014-08-01

A promoter polymorphism of the osteopontin (OPN) gene (rs28357094) has been associated with multiple inflammatory states, severity of Duchenne muscular dystrophy (DMD) and muscle size in healthy young adults. We sought to define the mechanism of action of the polymorphism, using allele-specific in vitro reporter assays in muscle cells, and a genotype-stratified intervention in healthy controls. In vitro reporter constructs showed the G allele to respond to estrogen treatment, whereas the T allele showed no transcriptional response. Young adult volunteers (n = 187) were enrolled into a baseline study, and subjects with specific rs28357094 genotypes enrolled into an eccentric muscle challenge intervention [n = 3 TT; n = 3 GG/GT (dominant inheritance model)]. Female volunteers carrying the G allele showed significantly greater inflammation and increased muscle volume change as determined by magnetic resonance imaging T1- and T2-weighted images after eccentric challenge, as well as greater decrement in biceps muscle force. Our data suggest a model where the G allele enables enhanced activities of upstream enhancer elements due to loss of Sp1 binding at the polymorphic site. This results in significantly greater expression of the pro-inflammatory OPN cytokine during tissue remodeling in response to challenge in G allele carriers, promoting muscle hypertrophy in normal females, but increased damage in DMD patients. © The Author 2014. Published by Oxford University Press.

4G/5G polymorphism of PAI-1 gene is associated with multiple organ dysfunction and septic shock in pneumonia induced severe sepsis: prospective, observational, genetic study

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2010-01-01

Introduction Activation of inflammation and coagulation are closely related and mutually interdependent in sepsis. The acute-phase protein, plasminogen activator inhibitor-1 (PAI-1) is a key element in the inhibition of fibrinolysis. Elevated levels of PAI-1 have been related to worse outcome in pneumonia. We aimed to evaluate the effect of functionally relevant 4G/5G polymorphism of PAI-1 gene in pneumonia induced sepsis. Methods We enrolled 208 Caucasian patients with severe sepsis due to pneumonia admitted to an intensive care unit (ICU). Patients were followed up until ICU discharge or death. Clinical data were collected prospectively and the PAI-1 4G/5G polymorphism was genotyped by polymerase chain reaction-restriction fragment length polymorphism technique. Patients were stratified according to the occurrence of multiple organ dysfunction syndrome, septic shock or death. Results We found that carriers of the PAI-1 4G/4G and 4G/5G genotypes have a 2.74-fold higher risk for multiple organ dysfunction syndrome (odds ratio [OR] 95% confidence interval [CI] = 1.335 - 5.604; p = 0.006) and a 2.57-fold higher risk for septic shock (OR 95%CI = 1.180 - 5.615; p = 0.018) than 5G/5G carriers. The multivariate logistic regression analysis adjusted for independent predictors, such as age, nosocomial pneumonia and positive microbiological culture also supported that carriers of the 4G allele have a higher prevalence of multiple organ dysfunction syndrome (adjusted odds ratio [aOR] = 2.957; 95%CI = 1.306 -6.698; p = 0.009) and septic shock (aOR = 2.603; 95%CI = 1.137 - 5.959; p = 0.024). However, genotype and allele analyses have not shown any significant difference regarding mortality in models non-adjusted or adjusted for acute physiology and chronic health evaluation (APACHE) II. Patients bearing the 4G allele had higher disseminated intravascular coagulation (DIC) score at admission (p = 0.007) than 5G/5G carriers. Moreover, in 4G allele carriers the length of ICU stay

4G/5G polymorphism of PAI-1 gene is associated with multiple organ dysfunction and septic shock in pneumonia induced severe sepsis: prospective, observational, genetic study.

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Madách, Krisztina; Aladzsity, István; Szilágyi, Agnes; Fust, George; Gál, János; Pénzes, István; Prohászka, Zoltán

2010-01-01

Activation of inflammation and coagulation are closely related and mutually interdependent in sepsis. The acute-phase protein, plasminogen activator inhibitor-1 (PAI-1) is a key element in the inhibition of fibrinolysis. Elevated levels of PAI-1 have been related to worse outcome in pneumonia. We aimed to evaluate the effect of functionally relevant 4G/5G polymorphism of PAI-1 gene in pneumonia induced sepsis. We enrolled 208 Caucasian patients with severe sepsis due to pneumonia admitted to an intensive care unit (ICU). Patients were followed up until ICU discharge or death. Clinical data were collected prospectively and the PAI-1 4G/5G polymorphism was genotyped by polymerase chain reaction-restriction fragment length polymorphism technique. Patients were stratified according to the occurrence of multiple organ dysfunction syndrome, septic shock or death. We found that carriers of the PAI-1 4G/4G and 4G/5G genotypes have a 2.74-fold higher risk for multiple organ dysfunction syndrome (odds ratio [OR] 95% confidence interval [CI] = 1.335 - 5.604; p = 0.006) and a 2.57-fold higher risk for septic shock (OR 95%CI = 1.180 - 5.615; p = 0.018) than 5G/5G carriers. The multivariate logistic regression analysis adjusted for independent predictors, such as age, nosocomial pneumonia and positive microbiological culture also supported that carriers of the 4G allele have a higher prevalence of multiple organ dysfunction syndrome (adjusted odds ratio [aOR] = 2.957; 95%CI = 1.306 -6.698; p = 0.009) and septic shock (aOR = 2.603; 95%CI = 1.137 - 5.959; p = 0.024). However, genotype and allele analyses have not shown any significant difference regarding mortality in models non-adjusted or adjusted for acute physiology and chronic health evaluation (APACHE) II. Patients bearing the 4G allele had higher disseminated intravascular coagulation (DIC) score at admission (p = 0.007) than 5G/5G carriers. Moreover, in 4G allele carriers the length of ICU stay of non-survivors was longer

Polymorphs and polymorphic cocrystals of temozolomide.

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Babu, N Jagadeesh; Reddy, L Sreenivas; Aitipamula, Srinivasulu; Nangia, Ashwini

2008-07-07

Crystal polymorphism in the antitumor drug temozolomide (TMZ), cocrystals of TMZ with 4,4'-bipyridine-N,N'-dioxide (BPNO), and solid-state stability were studied. Apart from a known X-ray crystal structure of TMZ (form 1), two new crystalline modifications, forms 2 and 3, were obtained during attempted cocrystallization with carbamazepine and 3-hydroxypyridine-N-oxide. Conformers A and B of the drug molecule are stabilized by intramolecular amide N--HN(imidazole) and N--HN(tetrazine) interactions. The stable conformer A is present in forms 1 and 2, whereas both conformers crystallized in form 3. Preparation of polymorphic cocrystals I and II (TMZBPNO 1:0.5 and 2:1) were optimized by using solution crystallization and grinding methods. The metastable nature of polymorph 2 and cocrystal II is ascribed to unused hydrogen-bond donors/acceptors in the crystal structure. The intramolecularly bonded amide N-H donor in the less stable structure makes additional intermolecular bonds with the tetrazine C==O group and the imidazole N atom in stable polymorph 1 and cocrystal I, respectively. All available hydrogen-bond donors and acceptors are used to make intermolecular hydrogen bonds in the stable crystalline form. Synthon polymorphism and crystal stability are discussed in terms of hydrogen-bond reorganization.

The influence of folate pathway polymorphisms on high-dose methotrexate-related toxicity and survival in children with non-Hodgkin malignant lymphoma

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Erculj, Nina; Kotnik, Barbara Faganel; Debeljak, Marusa; Jazbec, Janez; Dolzan, Vita

2014-01-01

Background We evaluated the influence of folate pathway polymorphisms on high-dose methotrexate (HD-MTX) related toxicity in paediatric patients with T-cell non-Hodgkin lymphoma (NHL). Patients and methods In total, 30 NHL patients were genotyped for selected folate pathway polymorphisms. Results Carriers of at least one MTHFR 677T allele had significantly higher MTX area under the time-concentration curve levels at third MTX cycle (P = 0.003). These patients were also at higher odds of leucopoenia (P = 0.006) or thrombocytopenia (P = 0.041) and had higher number of different HD-MTX-related toxicity (P = 0.035) compared to patients with wild-type genotype. Conclusions Our results suggest an important role of MTHFR 677C>T polymorphism in the development of HD-MTX-related toxicity in children with NHL. PMID:25177243

Genetic effect of interleukin-1 beta (C-511T) polymorphism on the structural covariance network and white matter integrity in Alzheimer's disease.

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Huang, Chi-Wei; Hsu, Shih-Wei; Tsai, Shih-Jen; Chen, Nai-Ching; Liu, Mu-En; Lee, Chen-Chang; Huang, Shu-Hua; Chang, Weng-Neng; Chang, Ya-Ting; Tsai, Wan-Chen; Chang, Chiung-Chih

2017-01-18

Inflammatory processes play a pivotal role in the degenerative process of Alzheimer's disease. In humans, a biallelic (C/T) polymorphism in the promoter region (position-511) (rs16944) of the interleukin-1 beta gene has been significantly associated with differences in the secretory capacity of interleukin-1 beta. In this study, we investigated whether this functional polymorphism mediates the brain networks in patients with Alzheimer's disease. We enrolled a total of 135 patients with Alzheimer's disease (65 males, 70 females), and investigated their gray matter structural covariance networks using 3D T1 magnetic resonance imaging and their white matter macro-structural integrities using fractional anisotropy. The patients were classified into two genotype groups: C-carriers (n = 108) and TT-carriers (n = 27), and the structural covariance networks were constructed using seed-based analysis focusing on the default mode network medial temporal or dorsal medial subsystem, salience network and executive control network. Neurobehavioral scores were used as the major outcome factors for clinical correlations. There were no differences between the two genotype groups in the cognitive test scores, seed, or peak cluster volumes and white matter fractional anisotropy. The covariance strength showing C-carriers > TT-carriers was the entorhinal-cingulum axis. There were two peak clusters (Brodmann 6 and 10) in the salience network and four peak clusters (superior prefrontal, precentral, fusiform, and temporal) in the executive control network that showed C-carriers covariance strength. The salience network and executive control network peak clusters in the TT group and the default mode network peak clusters in the C-carriers strongly predicted the cognitive test scores. Interleukin-1 beta C-511 T polymorphism modulates the structural covariance strength on the anterior brain network and entorhinal-interconnected network which were independent of the white

Cdx-2 polymorphism in Vitamin D Receptor gene was associated with serum 25-hydroxyvitamin D levels, bone mineral density and fracture in middle-aged and elderly Chinese women.

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Ling, Yan; Lin, Huandong; Aleteng, Qiqige; Ma, Hui; Pan, Baishen; Gao, Jian; Gao, Xin

2016-05-15

The aim of the current study was to examine the relationship between Cdx-2 polymorphism in the promoter region of the VDR gene and serum 25-hydroxyvitamin D (25(OH)D) levels, bone mineral density (BMD) and fracture in Chinese population. This was a cross-sectional study, which included 738 individuals (428 women and 310 men) aged 45 years or older. In women, the association of Cdx-2 polymorphism with serum 25(OH)D levels was significant adjusting for age, BMI, estimated glomerular filtration rate, menopausal status and season of blood collection (P = 0.002). Cdx-2 polymorphism was associated with lumbar spine BMD adjusted for age, BMI, menopausal status and serum 25(OH)D in women (P = 0.005). But it was not associated with femoral neck BMD or total hip BMD in women. In women, Cdx-2 polymorphism was also associated with fracture adjusted for age, BMI, menopausal status, serum 25(OH)D and total hip BMD (P = 0.03). Carriers of AA and AG genotypes was associated with a higher odds of fracture compared with the carriers of GG genotype (OR = 2.14, 95% CI 1.04-4.42 and OR = 1.90, 95% CI 1.03-3.51). In men, Cdx-2 polymorphism was not associated with serum 25(OH)D levels, BMD or fracture. Our results indicate that the association of Cdx-2 polymorphism in the VDR gene with serum 25(OH)D levels, BMD and fracture may have sex differences. Cdx-2 polymorphism in the VDR gene may affect the serum 25(OH)D concentrations and the risk of osteoporosis and fracture in middle-aged and elderly Chinese women. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

DNA Glycosylases Involved in Base Excision Repair May Be Associated with Cancer Risk in BRCA1 and BRCA2 Mutation Carriers

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Osorio, Ana; Milne, Roger L; Kuchenbaecker, Karoline

2014-01-01

Single Nucleotide Polymorphisms (SNPs) in genes involved in the DNA Base Excision Repair (BER) pathway could be associated with cancer risk in carriers of mutations in the high-penetrance susceptibility genes BRCA1 and BRCA2, given the relation of synthetic lethality that exists between one of th...

Effects of polymorphisms in ERCC1, ASE-1 and RAI on the risk of colorectal carcinomas and adenomas: a case control study

International Nuclear Information System (INIS)

Skjelbred, Camilla F; Sæbø, Mona; Nexø, Bjørn A; Wallin, Håkan; Hansteen, Inger-Lise; Vogel, Ulla; Kure, Elin H

2006-01-01

The risk of sporadic colorectal cancer is mainly associated with lifestyle factors and may be modulated by several genetic factors of low penetrance. Genetic variants represented by single nucleotide polymorphisms in genes encoding key players in the adenoma carcinoma sequence may contribute to variation in susceptibility to colorectal cancer. In this study, we aimed to evaluate whether the recently identified haplotype encompassing genes of DNA repair and apoptosis, is associated with increased risk of colorectal adenomas and carcinomas. We used a case-control study design (156 carcinomas, 981 adenomas and 399 controls) to test the association between polymorphisms in the chromosomal region 19q13.2-3, encompassing the genes ERCC1, ASE-1 and RAI, and risk of colorectal adenomas and carcinomas in a Norwegian cohort. Odds ratio (OR) and 95% confidence interval (CI) were estimated by binary logistic regression model adjusting for age and gender. The ASE-1 polymorphism was associated with an increased risk of adenomas, OR of 1.39 (95% CI 1.06–1.81), which upon stratification was apparent among women only, OR of 1.66 (95% CI 1.15–2.39). The RAI polymorphism showed a trend towards risk reduction for both adenomas (OR of 0.70, 95% CI 0.49–1.01) and carcinomas (OR of 0.49, 95% CI 0.21–1.13) among women, although not significant. Women who were homozygous carriers of the high risk haplotype had an increased risk of colorectal cancer, OR of 2.19 (95% CI 0.95–5.04) compared to all non-carriers although the estimate was not statistically significant. We found no evidence that the studied polymorphisms were associated with risk of adenomas or colorectal cancer among men, but we found weak indications that the chromosomal region may influence risk of colorectal cancer and adenoma development in women

Genetic Polymorphism of Secretoglobin SCGB1A1 and Development of Lung Pathology in Children

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N.K. Malaya

2014-02-01

Full Text Available The purpose of investigation — to study of A(38G genetic polymorphism of the first exon of secretoglobin SCGB1A1 in Crimean children and to identify the possible correlation between the degree of polymorphism and development of lung pathology (bronchial asthma and recurrent bronchitis. There were investigated DNA samples from children with bronchial asthma (75 persons, recurrent bronchitis (19 persons and healthy children (20 persons aged from 6 to 16 years. The genetic polymorphism was determined by polymerase chain reaction with method of allele discrimination with registration the results by electrophoresis. Frequency of allele combinations of genetic variants of studied polymorphism was different in patients with bronchial asthma, recurrent bronchitis and in control group. Thus, among patients with bronchial asthma the frequency of homozygous allele AA carriers is lower, and among patients with recurrent bronchitis it is higher then in control group. Contrary, the frequency of AG heterozygotes was higher among patients with bronchial asthma then in patients with recurrent bronchitis and in control group. Also the frequency of AG heterozygotes in patients with recurrent bronchitis is much lower than homozygotes. The obtained results can be used for prognostic purpose to evaluate the prospects of the obstructive syndrome development.

Macrophage Migration Inhibitory Factor Polymorphism Is Associated with Susceptibility to Inflammatory Coronary Heart Disease

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Kangting Ji

2015-01-01

Full Text Available Background. Macrophage migration inhibitory factor (MIF is a proinflammatory cytokine. This study explored the association of 173G/C polymorphism of the MIF gene with coronary heart disease (CHD. Methods. Sequencing was carried out after polymerase chain reaction with DNA specimens from 186 volunteers without CHD and 70 patients with CHD. Plasma MIF levels on admission were measured by ELISA. Patients were classified into either stable angina pectoris (SAP or unstable angina pectoris (UAP. Genotype distribution between cases and controls and the association of patients’ genotypes with MIF level and plaque stability were statistically evaluated (ethical approval number: 2012-01. Results. The frequency of the C genotype was higher in CHD patients than in the control (P=0.014. The frequency of the 173*CC genotype was higher in CHD patients than in the control (P=0.005. The plasma MIF level was higher in MIF173*C carriers than in MIF173*G carriers (P=0.033. CHD patients had higher plasma MIF levels than the control (P=0.000. Patients with UAP had higher plasma MIF levels than patients with SAP (P=0.014. Conclusions. These data suggest that MIF −173G/C polymorphism may be related to the development of CHD in a Chinese population. Plasma MIF level is a predictor of plaque stability. This trial is registered with NCT01750502 .

Behavioral and Neural Manifestations of Reward Memory in Carriers of Low-Expressing versus High-Expressing Genetic Variants of the Dopamine D2 Receptor

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Richter, Anni; Barman, Adriana; Wüstenberg, Torsten; Soch, Joram; Schanze, Denny; Deibele, Anna; Behnisch, Gusalija; Assmann, Anne; Klein, Marieke; Zenker, Martin; Seidenbecher, Constanze; Schott, Björn H.

2017-01-01

Dopamine is critically important in the neural manifestation of motivated behavior, and alterations in the human dopaminergic system have been implicated in the etiology of motivation-related psychiatric disorders, most prominently addiction. Patients with chronic addiction exhibit reduced dopamine D2 receptor (DRD2) availability in the striatum, and the DRD2 TaqIA (rs1800497) and C957T (rs6277) genetic polymorphisms have previously been linked to individual differences in striatal dopamine metabolism and clinical risk for alcohol and nicotine dependence. Here, we investigated the hypothesis that the variants of these polymorphisms would show increased reward-related memory formation, which has previously been shown to jointly engage the mesolimbic dopaminergic system and the hippocampus, as a potential intermediate phenotype for addiction memory. To this end, we performed functional magnetic resonance imaging (fMRI) in 62 young, healthy individuals genotyped for DRD2 TaqIA and C957T variants. Participants performed an incentive delay task, followed by a recognition memory task 24 h later. We observed effects of both genotypes on the overall recognition performance with carriers of low-expressing variants, namely TaqIA A1 carriers and C957T C homozygotes, showing better performance than the other genotype groups. In addition to the better memory performance, C957T C homozygotes also exhibited a response bias for cues predicting monetary reward. At the neural level, the C957T polymorphism was associated with a genotype-related modulation of right hippocampal and striatal fMRI responses predictive of subsequent recognition confidence for reward-predicting items. Our results indicate that genetic variations associated with DRD2 expression affect explicit memory, specifically for rewarded stimuli. We suggest that the relatively better memory for rewarded stimuli in carriers of low-expressing DRD2 variants may reflect an intermediate phenotype of addiction memory. PMID

Behavioral and Neural Manifestations of Reward Memory in Carriers of Low-Expressing versus High-Expressing Genetic Variants of the Dopamine D2 Receptor

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Anni Richter

2017-05-01

Full Text Available Dopamine is critically important in the neural manifestation of motivated behavior, and alterations in the human dopaminergic system have been implicated in the etiology of motivation-related psychiatric disorders, most prominently addiction. Patients with chronic addiction exhibit reduced dopamine D2 receptor (DRD2 availability in the striatum, and the DRD2 TaqIA (rs1800497 and C957T (rs6277 genetic polymorphisms have previously been linked to individual differences in striatal dopamine metabolism and clinical risk for alcohol and nicotine dependence. Here, we investigated the hypothesis that the variants of these polymorphisms would show increased reward-related memory formation, which has previously been shown to jointly engage the mesolimbic dopaminergic system and the hippocampus, as a potential intermediate phenotype for addiction memory. To this end, we performed functional magnetic resonance imaging (fMRI in 62 young, healthy individuals genotyped for DRD2 TaqIA and C957T variants. Participants performed an incentive delay task, followed by a recognition memory task 24 h later. We observed effects of both genotypes on the overall recognition performance with carriers of low-expressing variants, namely TaqIA A1 carriers and C957T C homozygotes, showing better performance than the other genotype groups. In addition to the better memory performance, C957T C homozygotes also exhibited a response bias for cues predicting monetary reward. At the neural level, the C957T polymorphism was associated with a genotype-related modulation of right hippocampal and striatal fMRI responses predictive of subsequent recognition confidence for reward-predicting items. Our results indicate that genetic variations associated with DRD2 expression affect explicit memory, specifically for rewarded stimuli. We suggest that the relatively better memory for rewarded stimuli in carriers of low-expressing DRD2 variants may reflect an intermediate phenotype of

Genetic Polymorphisms in Organic Cation Transporter 1 Attenuates Hepatic Metformin Exposure in Humans

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Sundelin, E. I.O.; Gormsen, Lars C; Jensen, J. B.

2017-01-01

the transporter protein OCT1, affect the hepatic distribution of metformin in humans. We performed noninvasive 11C-metformin positron emission tomography (PET)/computed tomography (CT) to determine hepatic exposure in 12 subjects genotyped for variants in SLC22A1. Hepatic distribution of metformin...... was significantly reduced after oral intake in carriers of M420del and R61C variants in SLC22A1 without being associated with changes in circulating levels of metformin. Our data show that genetic polymorphisms in transporter proteins cause variation in hepatic exposure to metformin, and it demonstrates......Metformin has been used successfully to treat type 2 diabetes for decades. However, the efficacy of the drug varies considerably from patient to patient and this may in part be due to its pharmacokinetic properties. The aim of this study was to examine if common polymorphisms in SLC22A1, encoding...

A new polymorphism in the GRP78 is not associated with HBV invasion

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Zhu, Xiao; Wang, Yi; Tao, Tao; Li, Dong-Pei; Lan, Fei-Fei; Zhu, Wei; Xie, Dan; Kung, Hsiang-Fu

2009-01-01

AIM: To examine the association between -86 bp (T > A) in the glucose-regulated protein 78 gene (GRP78) and hepatitis B virus (HBV) invasion. METHODS: DNA was genotyped for the single-nucleotide polymorphism by polymerase chain reaction followed by sequencing in a sample of 382 unrelated HBV carriers and a total of 350 sex- and age-matched healthy controls. Serological markers for HBV infection were determined by enzyme-linked immunosorbent assay kits or clinical chemistry testing. RESULTS: The distributions of allelotype and genotype in cases were not significantly different from those in controls. In addition, our findings suggested that neither alanine aminotransferase/hepatitis B e antigen nor HBV-DNA were associated with the allele/genotype variation in HBV infected individuals. CONCLUSION: -86 bp T > A polymorphism in GRP78 gene is not related to the clinical risk and acute exacerbation of HBV invasion. PMID:19842229

Association between XPF polymorphisms and cancer risk: a meta-analysis.

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Ting-Yan Shi

Full Text Available BACKGROUND: Xeroderma pigmentosum complementation group F (XPF or ERCC4 plays a key role in DNA repair that protects against genetic instability and carcinogenesis. A series of epidemiological studies have examined associations between XPF polymorphisms and cancer risk, but the findings remain inconclusive. METHODOLOGY/PRINCIPAL FINDINGS: In this meta-analysis of 47,639 cancer cases and 51,915 controls, by searching three electronic databases (i.e., MEDLINE, EMBASE and CNKI, we summarized 43 case-control studies from 29 publications on four commonly studied polymorphisms of XPF (i.e., rs1800067, rs1799801, rs2020955 and rs744154, and we did not find statistical evidence of any significant association with overall cancer risk. However, in stratification analyses, we found a significant association of XPF-rs1799801 with a reduced cancer risk in Caucasian populations (4,845 cases and 5,556 controls; recessive model: OR=0.87, 95% CI=0.76-1.00, P=0.049, P=0.723 for heterogeneity test, I(2 =0. Further genotype-phenotype correlation analysis showed that the homozygous variant CC genotype carriers had higher XPF expression levels than that of the TT genotype carriers (Student's t test for a recessive model: P=0.046. No publication bias was found by using the funnel plot and Egger's test. CONCLUSION: This meta-analysis suggests a lack of statistical evidence for the association between the four XPF SNPs and overall risk of cancers. However, XPF-rs1799801 may be associated with cancer risk in Caucasian populations, which needs to be further validated in single large, well-designed prospective studies.

Identification of citrullinaemia carrier and detection of a new silent mutation at 240bp position in ASS1 gene of normal Holstein cattle

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Kotikalapudi Rosaiah

2014-01-01

Full Text Available The autosomal recessive genetic disorders are regularly investigated especially in Indian Holstein and Holstein Crossbred bulls before they entered in semen collection so that a defective gene should not be transmitted to future generations. Bovine citrullinaemia first reported in Australia is a metabolic disorder as one of the enzymes, Argininosuccinate synthetase (ASS involved in urea cycle is impaired in function. The mutation responsible for citrullinemia has been characterized as a single-base substitution at 256bp (C>T in coding exon 3 of argininosuccinate synthetase 1 (ASS1 gene, which converts the CGA (arginine at 86 codon to TGA (stop codon. A Holstein bull during routine molecular screening was found to be carrier for Citrullinaemia that was confirmed by sequencing. This is a fresh case of Citrullinaemia carrier in addition to three cases reported earlier in India. Partial sequencing of coding exon 3 of a normal Holstein revealed a new silent polymorphism at 240bp position that does not change amino acid (Sarine AGC>AGT at 80 codon within exon 3 of ASS1 gene. The sequence of exon 3 of ASS1 gene in a normal Holstein exhibiting a new polymorphism was submitted to NCBI with accession No. KF933365. The presence of citrullinaemia carriers in Indian Holstein, though in very low frequency, emphasizing to continue the investigation of mutant gene in cattle population.

Linguistic grammar learning and DRD2-TAQ-IA polymorphism.

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Patrick C M Wong

Full Text Available As research into the neurobiology of language has focused primarily on the systems level, fewer studies have examined the link between molecular genetics and normal variations in language functions. Because the ability to learn a language varies in adults and our genetic codes also vary, research linking the two provides a unique window into the molecular neurobiology of language. We consider a candidate association between the dopamine receptor D2 gene (DRD2 and linguistic grammar learning. DRD2-TAQ-IA polymorphism (rs1800497 is associated with dopamine receptor D2 distribution and dopamine impact in the human striatum, such that A1 allele carriers show reduction in D2 receptor binding relative to carriers who are homozygous for the A2 allele. The individual differences in grammatical rule learning that are particularly prevalent in adulthood are also associated with striatal function and its role in domain-general procedural memory. Therefore, we reasoned that procedurally-based grammar learning could be associated with DRD2-TAQ-IA polymorphism. Here, English-speaking adults learned artificial concatenative and analogical grammars, which have been respectively associated with procedural and declarative memory. Language learning capabilities were tested while learners' neural hemodynamic responses were simultaneously measured by fMRI. Behavioral learning and brain activation data were subsequently compared with the learners' DRD2 (rs1800497 genotype. Learners who were homozygous for the A2 allele were better at concatenative (but not analogical grammar learning and had higher striatal responses relative to those who have at least one A1 allele. These results provide preliminary evidence for the neurogenetic basis of normal variations in linguistic grammar learning and its link to domain-general functions.

Impact of HSD11B1 polymorphisms on BMI and components of the metabolic syndrome in patients receiving psychotropic treatments

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Quteineh, Lina; Vandenberghe, Frederik; Saigi Morgui, Nuria; Delacré taz, Auré lie; Choong, Eva; Gholam-Rezaee, Mehdi; Magistretti, Pierre J.; Bondolfi, Guido; Von Gunten, Armin; Preisig, Martin A.; Castelao, Enrique; Vollenweider, Peter; Waeber, Gé rard; Bochud, Murielle; Kutalik, Zoltá n; Conus, Philippe O.; Eap, Chin Bin

2015-01-01

Background Metabolic syndrome (MetS) associated with psychiatric disorders and psychotropic treatments represents a major health issue. 11β-Hydroxysteroid dehydrogenase type 1 (11β-HSD1) is an enzyme that catalyzes tissue regeneration of active cortisol from cortisone. Elevated enzymatic activity of 11β-HSD1 may lead to the development of MetS. Methods We investigated the association between seven HSD11B1 gene (encoding 11β-HSD1) polymorphisms and BMI and MetS components in a psychiatric sample treated with potential weight gain-inducing psychotropic drugs (n=478). The polymorphisms that survived Bonferroni correction were analyzed in two independent psychiatric samples (n R1 =168, n R2 =188) and in several large population-based samples (n 1 =5338; n 2 =123 865; n 3 >100 000). Results HSD11B1 rs846910-A, rs375319-A, and rs4844488-G allele carriers were found to be associated with lower BMI, waist circumference, and diastolic blood pressure compared with the reference genotype (P corrected <0.05). These associations were exclusively detected in women (n=257) with more than 3.1 kg/m 2, 7.5 cm, and 4.2 mmHg lower BMI, waist circumference, and diastolic blood pressure, respectively, in rs846910-A, rs375319-A, and rs4844488-G allele carriers compared with noncarriers (P corrected <0.05). Conversely, carriers of the rs846906-T allele had significantly higher waist circumference and triglycerides and lower high-density lipoprotein-cholesterol exclusively in men (P corrected =0.028). The rs846906-T allele was also associated with a higher risk of MetS at 3 months of follow-up (odds ratio: 3.31, 95% confidence interval: 1.53-7.17, P corrected =0.014). No association was observed between HSD11B1 polymorphisms and BMI and MetS components in the population-based samples. Conclusions Our results indicate that HSD11B1 polymorphisms may contribute toward the development of MetS in psychiatric patients treated with potential weight gain-inducing psychotropic drugs, but do not

Analysis of the relationship between interleukin polymorphisms within miRNA-binding regions and alcoholic liver disease.

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Novo-Veleiro, I; Cieza-Borrella, C; Pastor, I; González-Sarmiento, R; Laso, F-J; Marcos, M

2018-05-01

Alcohol consumption promotes inflammation through the Toll-like receptor 4 (TLR4)/nuclear factor (NF)-?B pathway, leading to organic damage. Some micro-RNA (miRNA) molecules modulate this inflammatory response by downregulating TLR4/NF-?B pathway mediators, like interleukins (ILs). Thus, polymorphisms within IL genes located near miRNA binding sites could modify the risk of ethanol-induced damage. The present study analyzed potential relationships between alcoholism or alcoholic liver disease (ALD) and IL12B 2124 G>T (rs1368439), IL16 5000 C>T (rs1131445), IL1R1 3114 C>T (rs3917328), and NFKB1 3400 A>G (rs4648143) polymorphisms. The study included 301 male alcoholic patients and 156 male healthy volunteers. Polymorphisms were genotyped using TaqMan ® PCR assays for allelic discrimination. Allele and genotype frequencies were compared between groups. Logistic regression analysis was performed to analyze the inheritance model. Analysis of the IL1R1 (rs3917328) polymorphism showed that the proportion of alleleT carriers (CT and TT genotypes) was higher in healthy controls (9.7%) than in alcoholic patients (6.5%; P=.042). However, multivariable logistic regression analyses did not yield a significant result. No differences between groups were found for other analyzed polymorphisms. Our study describes, for the first time, the expected frequencies of certain polymorphisms within miRNA-binding sites in alcoholic patients with and without ALD. Further studies should be developed to clarify the potential relevance of these polymorphisms in alcoholism and ALD development. Copyright © 2018 Elsevier España, S.L.U. and Sociedad Española de Medicina Interna (SEMI). All rights reserved.

The CXCR2 Gene Polymorphism Is Associated with Stroke in Patients with Essential Hypertension

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Yanina R. Timasheva

2015-10-01

Full Text Available Hypertension is the major risk factor for stroke, and genetic factors contribute to its development. Inflammation has been hypothesized to be the key link between blood pressure elevation and stroke. We performed an analysis of the association between inflammatory mediator gene polymorphisms and the incidence of stroke in patients with essential hypertension (EH. The study group consisted of 625 individuals (296 patients with noncomplicated EH, 71 hypertensive patients with ischemic stroke, and 258 control subjects. Both patients and controls were ethnic Tatars originating from the Republic of Bashkortostan (Russian Federation. The analysis has shown that the risk of ischemic stroke was associated with the CXCR2 rs1126579 polymorphism. Our results indicate that among patients with EH, the heterozygous genotype carriers had a higher risk of stroke (OR = 1.72, 95% CI 1.01-2.92, whereas the CXCR2*C/C genotype was protective against stroke (OR = 0.32, 95% CI 0.12-0.83. As shown by the gene-gene interaction analysis, the CXCR2 rs1126579 polymorphism was also present in all genotype/allele combinations associated with the risk of stroke. Genetic patterns associated with stroke also included polymorphisms in the CCL2, CCL18, CX3CR1, CCR5, and CXCL8(IL8 genes, although no association between these loci and stroke was detected by individual analysis.

Crystal engineering of lactose using electrospray technology: carrier for pulmonary drug delivery.

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Patil, Sharvil; Mahadik, Abhijeet; Nalawade, Pradeep; More, Priyesh

2017-12-01

Dry powder inhalers (DPIs) consisting of a powder mixture containing coarse carrier particles (generally lactose) and micronized drug particles are used for lung drug delivery. The effective drug delivery to the lungs depends on size and shape of carrier particles. Thus, various methods have been proposed for engineering lactose particles to enhance drug delivery to lungs. The objective of current work was to assess suitability of electrospray technology toward crystal engineering of lactose. Further, utility of the prepared lactose particles as a carrier in DPI was evaluated. Saturated lactose solutions were electrosprayed to obtain electrosprayed lactose (EL) particles. The polymorphic form of EL was determined using Fourier transform infrared spectroscopy, powder X-ray diffractometry, and differential scanning calorimetry. In addition, morphological, surface textural, and flow properties of EL were determined using scanning electron microscopy and Carr's index, respectively. The aerosolization properties of EL were determined using twin-stage impinger and compared with commercial lactose particles [Respitose ® (SV003, Goch, Germany)] used in DPI formulations. EL was found to contain both isomers (α and β) of lactose having flow properties comparable to Respitose ® (SV003). In addition, the aerosolization properties of EL were found to be significantly improved when compared to Respitose ® (SV003) which could be attributed to morphological (high elongation ratio) and surface characteristic (smooth surface) alterations induced by electrospray technology. Electrospray technology can serve as an alternative technique for continuous manufacturing of engineered lactose particles which can be used as a carrier in DPI formulations.

Relation between radiotherapy-induced acute injury of mucosa of nasopharyngeal carcinoma and p53 polymorphisms

International Nuclear Information System (INIS)

Wang Changsheng; Xiao Shaowen; Zhang Shanwen

2007-01-01

Objective: To explore the relation between p53 genetic polymorphisms and radiotherapy-induced acute injury of mucosa of oral cavity mucosa. Methods: The total of 56 patients with NPC treated by radiotherapy alone or with chemoradiotherapy synchronically were genotyped for the p53 codon 72 pro-Arg SNP using PCR-RFLP assays, and were ranked according to the acute injury of oral cavity mucosa. Results: There was no difference in acute injury of oral cavity mucosa between the p53 Pro allele carriers and the other carriers (P>0.05); the high single dose (P<0.01) and concomitant chemoradiotherapy (P<0.05) resulted in increase in acute injury of oral cavity mucosa. Conclusion: Those results suggest that p53 SNP may not associate with radiotherapeutic acute injury of oral cavity mucosa. (authors)

Obesity risk prediction among women of Upper Egypt: The impact of serum vaspin and vaspin rs2236242 gene polymorphism.

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Abdel Ghany, Soad M; Sayed, Ayat A; El-Deek, Sahar E M; ElBadre, Hala M; Dahpy, Marwa A; Saleh, Medhat A; Sharaf El-Deen, Hanan; Mustafa, Mohamed H

2017-08-30

Vaspin is an adipokine that is potentially linking obesity, insulin resistance, metabolic syndrome and type-2 diabetes. The present study aimed to investigate the impact of vaspin rs2236242 gene polymorphism on the risk of obesity, diabetes, their metabolic traits, and serum vaspin levels in a sample of Upper Egyptian women. A total of 224 subjects, 112 obese (62 non diabetics, 50 diabetics) and 112 controls were included in this case control study. Vaspin gene rs2236242 polymorphism was performed using tetra-amplification refractory mutation system-polymerase chain reaction (T-ARMS-PCR) and serum vaspin levels were estimated by ELISA. The minor (A) allele of vaspin rs2236242 gene polymorphism was significantly lower in obese (30.8%) than controls (43.7%) (P=0.005). The protective effect was evident in dominant and recessive inheritance models (TT vs TA+AA, P=0.004 and TT+TA vs AA, P=0.036). After adjusting genotypes for diabetes there were no significant association between vaspin rs2236242 gene polymorphism and obesity but significant association was maintained in the obese diabetics. Vaspin serum levels were found to be lower in minor protective (AA) genotype carriers than the other two genotypes (Pobese diabetics and non-diabetics than controls (Pobesity and diabetes but this relation is largely ascribed to its effect on insulin resistance. The serum vaspin concentration was lower in minor protective allele carriers. To the best of our knowledge, this is the first study of vaspin SNP in Upper Egyptian women. The entire understanding of vaspin intimate mechanistic action might enable the development of novel etiology-based treatment strategies for obesity, the complex genetic trait. Copyright © 2017 Elsevier B.V. All rights reserved.

Association of functional polymorphisms from brain-derived neurotrophic factor and serotonin-related genes with depressive symptoms after a medical stressor in older adults.

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Kerri S Rawson

Full Text Available Depressive symptoms are common in older adults after a disabling medical event and interfere with rehabilitation and recovery from the disability. This prospective study examined the role of genetic polymorphisms implicated in synaptic integrity and stress-associated depression as predictors of depressive symptoms after hip fracture. We recruited healthy comparisons from the community and participants with hip fracture after surgical fixation from Saint Louis, Missouri hospitals. We examined the valine (Val to methionine (Met polymorphism in brain-derived neurotrophic factor (BDNF, serotonin 1A receptor (5HT1a-rs6295 polymorphism, and the serotonin transporter-linked polymorphic region (5HTTLPR interaction with the rs25531 A to G single nucleotide polymorphism (5HTTLPR-rs25531 as predictors of depressive symptoms. We also examined whether depressive symptoms mediate the influence of BDNF genotype on functional recovery. Among 429 participants with hip fracture, BDNF Met/Met carriers developed significantly more depressive symptoms than Val/Val carriers during a four-week period after the fracture (p=.012. BDNF genotype also predicted functional recovery over the ensuing year, mediated by its effects on depressive symptoms (CI: 0.07-3.37. Unlike prior studies of stressful life events, the S' 5HTTLPR-rs25531 variant did not predict higher levels of depressive symptoms; instead, we report an exploratory finding of an epistatic effect between BDNF and 5HTTLPR-rs25531 whereby the compounded effects of two LA alleles and BDNF Met/Met genotype elevate risk of depressive symptoms after hip fracture (p=.006. No differences between 5HT1a genotypes were found. Our findings suggest plasticity-related genetic factors contribute to the neural mechanisms of mental and functional well-being after a disabling medical stressor.

TS gene polymorphisms are not good markers of response to 5-FU therapy in stage III colon cancer patients.

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Fariña-Sarasqueta, A; Gosens, M J E M; Moerland, E; van Lijnschoten, I; Lemmens, V E P P; Slooter, G D; Rutten, H J T; van den Brule, Adriaan J C

2011-08-01

Although the predictive and prognostic value of thymidylate synthase (TS) expression and gene polymorphism in colon cancer has been widely studied, the results are inconclusive probably because of methodological differences. With this study, we aimed to elucidate the role of TS gene polymorphisms genotyping in therapy response in stage III colon carcinoma patients treated with 5-FU adjuvant chemotherapy. 251 patients diagnosed with stage III colon carcinoma treated with surgery followed by 5-FU based adjuvant therapy were selected. The variable number of tandem repeats (VNTR) and the single nucleotide polymorphism (SNP) in the 5'untranslated region of the TS gene were genotyped. There was a positive association between tumor T stage and the VNTR genotypes (p = 0.05). In both univariate and multivariate survival analysis no effects of the studied polymorphisms on survival were found. However, there was an association between both polymorphisms and age. Among patients younger than 60 years, the patients homozygous for 2R seemed to have a better overall survival, whereas among the patients older than 67 this longer survival was seen by the carriers of other genotypes. We conclude that the TS VNTR and SNP do not predict response to 5-FU therapy in patients with stage III colon carcinoma. However, age appears to modify the effects of TS polymorphisms on survival.

Polymorphisms in chemokine and receptor genes and gastric cancer risk and survival in a high risk Polish population.

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Gawron, Andrew J; Fought, Angela J; Lissowska, Jolanta; Ye, Weimin; Zhang, Xiao; Chow, Wong-Ho; Beane Freeman, Laura E; Hou, Lifang

2011-03-01

To examine if genetic variations in chemokine receptor and ligand genes are associated with gastric cancer risk and survival. The study included 298 cases and 417 controls from a population-based study of gastric cancer conducted in Warsaw, Poland in 1994-1996. We investigated seven single nucleotide polymorphisms in a chemokine ligand (CXCL12) and chemokine receptor (CCR2, CCR5, CX3CR1) genes and one frameshift deletion (CCR5) in blood leukocyte DNA in relation to gastric cancer risk and survival. Genotyping was conducted at the NCI Core Genotyping Facility. Odds ratios and 95% confidence intervals were computed using univariate and multivariate logistic regression models. Survival analysis was performed using Cox proportional hazards models. Gastric cancer risk was not associated with single chemokine polymorphisms. A CCR5 haplotype that contained the common alleles of IVS1+151 G>T (rs2734648), IVS2+80 C>T (rs1800024) and minor allele of IVS1+246 A>G (rs1799987) was associated with a borderline significantly increased risk (OR = 1.5, 95% CI: 1.0?2.2). For gastric cancer cases, there was a greater risk of death for carriers of the minor alleles of CCR2 Ex2+241 G>A (rs1799864) (HR = 1.5, 95% CI: 1.1-2.1) and CCR5 IVS2+80 C>T (rs1800024) (HR = 1.5, 95% CI: 1.1-2.1). Carriers of the CCR5 minor allele of IVS1+151 G>T (rs2734648) had a decreased risk of death compared to homozygote carriers of the common allele (HR = 0.8, 95% CI: 0.6-1.0). Our findings do not support an association between gastric cancer risk and single chemokine genetic variation. The observed associations between cancer risk and a CCR5 haplotype and between survival and polymorphisms in CCR2 and CCR5 need replication in future studies.

Influence of paraoxonase-1 Q192R and cytochrome P450 2C19 polymorphisms on clopidogrel response

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Li L

2012-02-01

Full Text Available Rolf P Kreutz1,2, Perry Nystrom2, Yvonne Kreutz2, Jia Miao2, Zeruesenay Desta2, Jeffrey A Breall1, Lang Li2, ChienWei Chiang2, Richard Kovacs1, David A Flockhart2, Yan Jin21Krannert Institute of Cardiology, 2Division of Clinical Pharmacology, Indiana University School of Medicine, Indianapolis, IN, USABackground: The metabolic activation of clopidogrel is a two-step process. It has been suggested that paraoxonase-1 (PON1 is a rate-limiting enzyme in the conversion of 2-oxo-clopidogrel to an active thiol metabolite. Conflicting results have been reported in regard to (1 the association of a common polymorphism of PON1 (Q192R with reduced rates of coronary stent thrombosis in patients taking clopidogrel and (2 its effects on platelet inhibition in patient populations of European descent. Methods: Blood samples from 151 subjects of mixed racial background with established coronary artery disease and who received clopidogrel were analyzed. Platelet aggregation was determined with light transmittance aggregometry and VerifyNow® P2Y12 assay. Genotyping for cytochrome P450 2C19 (CYP2C19*2 and *3 and PON1 (Q192R polymorphisms was performed.Results: Carriers of CYP2C19*2 alleles exhibited lower levels of platelet inhibition and higher on-treatment platelet aggregation than noncarriers. There was no significant difference in platelet aggregation among PON1 Q192R genotypes. Homozygous carriers of the wild-type variant of PON1 (QQ192 had similar on-treatment platelet reactivity to carriers of increased-function variant alleles during maintenance clopidogrel dosing, as well as after administration of a clopidogrel 600 mg loading dose.Conclusion: CYP2C19*2 allele is associated with impaired platelet inhibition by clopidogrel and high on-treatment platelet aggregation. PON1 (Q192R polymorphism does not appear to be a significant determinant of clopidogrel response.Keywords: PON1, platelet, aggregation, cytochrome P450 enzymes

Polymorphisms in CISH gene are associated with persistent hepatitis B virus infection in Han Chinese population.

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Hu, Zhangyong; Yang, Jinliang; Wu, Yangping; Xiong, Guolian; Wang, Yali; Yang, Jun; Deng, Lan

2014-01-01

Cytokine-inducible SRC homology 2 domain protein (CISH) is the first member of the suppressors of cytokine signaling (SOCS) protein family. An association between multiple CISH polymorphisms and susceptibility to infectious diseases has been reported. This study aimed to investigate the possible association of these single nucleotide polymorphisms (SNPs) in CISH gene with different outcomes of Hepatitis B virus (HBV) infection. 1019 unrelated Chinese Han subjects, including 240 persistent asymptomatic HBV carriers, 217 chronic hepatitis B patients, 137 HBV-related liver cirrhosis patients, and 425 cases of spontaneously recovered HBV as controls, were studied. Four SNPs (rs622502, rs2239751, rs414171 and rs6768300) in CISH gene were genotyped with the snapshot technique. Transcriptional activity of the CISH promoter was assayed in vitro using the dual-luciferase reporter assay system. At position rs414171, A allele and AA genotype frequencies were significantly higher in the HBV-resolved group as compared to the persistent HBV infection group. At position rs2239751, TT genotype was further observed in the HBV-resolved group. Using asymptomatic HBV carriers as controls, our results indicated that the rs414171 and rs2239751 polymorphisms were unrelated to HBV progression. The other two SNPs (rs622502 and rs6768300) showed no association with persistent HBV infection. Haplotype analysis revealed that the GGCA haplotype was associated with spontaneous clearance of HBV in this population. Moreover, luciferase activity was significantly higher in the PGL3-Basic-rs414171T construct as compared to the PGL3-Basic-rs414171A construct (pCISH gene were associated with persistent HBV infection in Han Chinese population, but not with HBV progression.

TP53 codon 72 polymorphism as a risk factor for cardiovascular disease in a Brazilian population

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M.A.C. Smith

2007-11-01

Full Text Available TP53, a tumor suppressor gene, has a critical role in cell cycle, apoptosis and cell senescence and participates in many crucial physiological and pathological processes. Identification of TP53 polymorphism in older people and age-related diseases may provide an understanding of its physiology and pathophysiological role as well as risk factors for complex diseases. TP53 codon 72 (TP53:72 polymorphism was investigated in 383 individuals aged 66 to 97 years in a cohort from a Brazilian Elderly Longitudinal Study. We investigated allele frequency, genotype distribution and allele association with morbidities such as cardiovascular disease, type II diabetes, obesity, neoplasia, low cognitive level (dementia, and depression. We also determined the association of this polymorphism with serum lipid fractions and urea, creatinine, albumin, fasting glucose, and glycated hemoglobin levels. DNA was isolated from blood cells, amplified by PCR using sense 5'-TTGCCGTCCCAAGCAATGGATGA-3' and antisense 5'-TCTGGGAAGGGACAGAAGATGAC-3' primers and digested with the BstUI enzyme. This polymorphism is within exon 4 at nucleotide residue 347. Descriptive statistics, logistic regression analysis and Student t-test using the multiple comparison test were used. Allele frequencies, R (Arg = 0.69 and P (Pro = 0.31, were similar to other populations. Genotype distributions were within Hardy-Weinberg equilibrium. This polymorphism did not show significant association with any age-related disease or serum variables. However, R allele carriers showed lower HDL levels and a higher frequency of cardiovascular disease than P allele subjects. These findings may help to elucidate the physiopathological role of TP53:72 polymorphism in Brazilian elderly people.

Interaction between interleukin-10 (IL-10) polymorphisms and dietary fibre in relation to risk of colorectal cancer in a Danish case-cohort study

DEFF Research Database (Denmark)

Andersen, Vibeke; Egeberg, Rikke; Tjonneland, Anne

2012-01-01

-inflammatory cytokine. We wanted to test if dietary factors and IL10 polymorphisms interact in relation to colorectal carcinogenesis. Methods: The functional IL10 polymorphism C-592A (rs1800872) and the marker rs3024505 were assessed in relation to diet and lifestyle in a nested case-cohort study of 378 CRC cases...... and 775 randomly selected participants from a prospective study of 57,053 persons. Genotyping data on the IL10 polymorphism C-592A, smoking and nonsteroidal anti-inflammatory drugs (NSAID) was retrieved from Vogel et al. (Mutat Res, 2007; 624: 88). Incidence rate ratios (IRR) and 95% Confidence Interval...... (95% CI) were calculated. Results: No associations were found between the IL10 rs3024505 polymorphism and risk of CRC. There was interaction between rs3024505 and dietary fibre (P-value for interaction = 0.01). IL10 rs3024505 homozygous wildtype carriers were at 27% reduced risk of CRC per 10 g fibre...

Evaluation of the Role of -137G/C Single Nucleotide Polymorphism (rs187238 and Gene Expression Levels of the IL-18 in Patients with Coronary Artery Disease

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Fatemeh Hoseini

2018-03-01

Full Text Available Objectives: Interleukin-18 (IL-18 is a proinflammatory and proatherogenic cytokine, and its genetic variations may contribute to the development of coronary artery disease (CAD. We sought to investigate the role of -137G/C polymorphism and gene expression levels of IL-18 in patients with CAD. Methods: The study population included 100 patients with angiographically proven CAD and 100 matched controls. Total RNA and DNA were extracted from leukocytes using appropriate kits. The genotype of -137G/C polymorphism and gene expression level of IL-18 was determined using allele-specific polymerase chain reaction (PCR and real-time (RT-PCR assay, respectively. Results: The genotypic and allelic distribution of IL-18 -137G/C polymorphism was not significantly different between the two groups (p > 0.050. Moreover, the -137G/C polymorphism did not increase the risk of CAD in dominant and recessive genetic models (p > 0.050. However, subgroup analysis of CAD patients revealed that the IL-18 -137G/C polymorphism was significantly associated with increased risk of CAD in hypertensive patients (odds ratio (OR = 7.51; 95% confidence interval (CI: 1.24–25.17; p = 0.019 and smokers (OR = 4.90; 95% CI: 1.21–19.70; p = 0.031 but not in the diabetic subpopulation (p = 0.261. The genotype distribution of IL-18 -137G/C genetic polymorphism was significantly different among patients with one, two, and three stenotic vessels (p < 0.050. The gene expression level of IL-18 was significantly higher in the CAD group than the control group (p < 0.001. Moreover, the carriers of CC genotype had significantly lower gene expression levels of IL-18 than carriers of GG genotype (p < 0.050.Conclusions: The -137G/C polymorphism of IL-18 may be associated with the CAD risk in hypertensive and smoker subgroup of CAD patients. The -137G/C polymorphism seems to play an important role in determining the severity of CAD. Increased IL-18 gene expression level is a significant risk

Association of a miRNA-137 Polymorphism with Schizophrenia in a Southern Chinese Han Population

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Guoda Ma

2014-01-01

Full Text Available Both genome wide association study (GWAS and biochemical studies of Caucasian populations indicate a robust association between the miR-137 genetic variant rs1625579 and schizophrenia, but inconsistent results have been reported. To assay the association between this variant and schizophrenia, we genotyped 611 schizophrenic patients from Southern Chinese Han population for the risk single nucleotide polymorphism (SNP rs1625579 using the SNaPshot technique and compared the clinical profiles of different genotypes. Additionally, a meta-analysis was performed using the combined sample groups from five case-control publications and the present study. Both the genotype and allele distributions of the rs1625579 SNP were significantly different between patients and controls (P=0.036 and 0.026, SNP. TT genotype carriers showed slightly lower Brief Assessment of Cognition in Schizophrenia- (BACS- derived working memory performance than G carriers (15.58 ± 9.56 versus 19.71 ± 8.18, P=0.045. In the meta-analysis, we observed a significant association between rs1625579 and schizophrenia under different genetic models (all P<0.05. The results of our study and meta-analysis provide convincing evidence that rs1625579 is significantly associated with schizophrenia. Furthermore, the miR-137 polymorphism influences the working memory performance of schizophrenic patients in a Chinese Han population.

Diversity of apolipoprotein E genetic polymorphism significance on cardiovascular risk is determined by the presence of metabolic syndrome among hypertensive patients.

Science.gov (United States)

Teixeira, Andrei Alkmim; Marrocos, Mauro Sergio; Quinto, Beata Marie Redublo; Dalboni, Maria Aparecida; Rodrigues, Cassio Jose de Oliveira; Carmona, Silmara de Melo; Kuniyoshi, Mariana; Batista, Marcelo Costa

2014-11-20

Hypertension has a significant relevance as a cardiovascular risk factor. A consistent increase on world's Metabolic Syndrome (MetS) incidence has been associated with an epidemic cardiovascular risk in different populations. Dislipidemia plays a major role determining the epidemic CV burden attributed to MetS. Apolipoprotein E (ApoE) is involved on cholesterol and triglycerides metabolism regulation. Once ApoE polymorphism may influence lipid metabolism, it is possible that it brings on individual susceptibility consequences for the development of MetS and cardiovascular risk. The objective of the study is to measure the discriminatory power of ApoE polymorphism in determining cardiovascular risk stratification based on the presence MetS in a cohort of hypertensive patients. It was enrolled 383 patients, divided in two groups, classified by MetS presence (IDF criteria): Group 1: 266 patients with MetS (MetS +) and Group 2: 117 patients without Mets (MetS -). Patient's data were collected by clinical evaluation, physical exam, file reviews and laboratory testing. Polymorphic ApoE analysis was performed by PCR amplification. Groups were compared on clinical and laboratory characteristics as well as allele and genotype distribution towards ApoE polymorphism. Mets CVD prevalence was analysed according to E4 allele prevalence. The results evidenced 184 men (48%), 63,7% whites, 45,1% diabetics and 11,7% of patients were smokers. Mean age was 64,0 ± 12,0 years. When genotypic distribution was analyzed, E3/3 genotype and E3 allele frequencies were more prevalent. Among patients with MetS, we observed an independent association between CVD prevalence and E4 allele frequency (OR 2.42 (1.17- 5.0, p < 0,05)). On the opposite direction, in those without MetS, there was lesser CVD burden in E4 allele carriers (OR 0,14 (0,02-0,75)). These associations remained significant even after confounding factor corrections. The results presented demonstrate that the association

VEGF 936C > T Polymorphism and Association of BI-RADS Score in Women with Suspected Breast Cancer

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M. Wehrschuetz

2009-01-01

Full Text Available Purpose Vascular endothelial growth factor (VEGF is a potent regulator of angiogenesis and thereby involved in the development and progression of solid tumors. A 936C> T polymorphism in the VEGF gene has been associated with reduced VEGF plasma levels. Purpose of the present study was to analyze the potential association between VEGF genotype and radiological appearance of breast lesions by mammography. Materials and Methods Fifty two women with 54 suspected breast lesions were analyzed by the use of mammography with the standard breast imaging reporting and data systems (BI-RADS. Germline VEGF genotype was determined in all subjects by allele-specific digestion of amplification products. An open biopsy was performed on all lesions. Results VEGF CC, CT and TT genotypes were found in 41 (79%, 9 (17% and 2 (4% patients. By mammography 26, 16 and 12 suspected breast lesions were classified as BI-RADS scores 3, 4 and 5, respectively. Both carriers of the TT genotype were classified as BI-RADS 5, whereas among CT or CC carriers, BI-RADS scores 3, 4 and 5 were found in 26, 16 and 10 subjects (P T polymorphism seems to be associated with a high BI-RADS score in women with suspicious breast lesions.

Polymorphism of the ACE gene and the risk of obstructive sleep apnoea.

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Chmielewska, Izabela; Mlak, Radosław; Krawczyk, Paweł; Czukiewska, Ewa; Milanowski, Janusz

2013-01-01

Obstructive sleep apnoea/hypopnea syndrome (OSA) is characterized by obstruction of the upper airway during sleep, resulting in repetitive breathing pauses accompanied by oxygen desaturation and arousal from sleep. Among the candidate genes affecting the risk of OSA, genes whose polymorphisms influence the development of diseases with similar pathogenesis such as OSA could be listed: APOE, genes for leptin and leptin receptor, TNFA1, ADRB2 and ACE (gene for angiotensin-converting enzyme). Until now there has been a confirmed relationship between ACE gene polymorphism and cardiovascular diseases, but its effect on the incidence of OSA is debatable. The aim of this study was to investigate the effect of ACE gene insertion/deletion (I/D) polymorphism on the risk of OSA. Fifty-five patients with confirmed diagnose of OSA and qualified to CPAP therapy entered the study. The control group included 50 subjects who did not complain of any sleep related symptoms. Diagnose of OSA was set on the basis of full overnight polysomnography together with Epworth Sleepiness Scale according to American Academy of Sleep Medicine guidelines. DNA was isolated from peripheral blood leukocytes with Qiagen DNA mini Kit. ACE gene polymorphism was determined in genomic DNA using allele specific polymerase chain reaction. Different sizes of PCR products were observed on agarose gel electrophoresis. There were non-significant differences in the frequency of ACE genotypes. However, allele D had significantly lower prevalence in the study group than in the control group. (χ(2) = 4.25 p = 0.04). Moreover, I allele carriers had a threefold greater risk of developing OSA (HR = 2.748, 95% CI = 1.029-7.340, p gene polymorphism might be useful to determine the risk of developing OSA in clinically predisposed patients.

The CYP1A2 -163C>A polymorphism does not alter the effects of caffeine on basketball performance

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Puente, Carlos; Abián-Vicén, Javier; Lara, Beatriz; Salinero, Juan José

2018-01-01

Purpose The aim of this investigation was to analyze the influence of the genetic variations of the -163C>A polymorphism of the CYP1A2 gene on the ergogenic effects of caffeine in elite basketball players. Methods Nineteen elite basketball players (10 men and 9 women) ingested 3 mg⋅kg-1 of caffeine or a placebo 60 min before performing 10 repetitions of the following series: the Abalakov jump test followed by the Change-of-Direction and Acceleration Test (CODAT). The players then competed in a 20-min simulated basketball game. Self-perceived performance and side effects were recorded by questionnaires after the trials. The effects of caffeine on basketball performance were established according to players’ CYP1A2 genotype (rs762551): AA homozygotes (n = 10) and C-allele carriers (n = 9). Results In the 10 repetitions, caffeine increased Abalakov jump height by a mean of 2.9±3.6% in AA homozygotes (p = 0.03) while this effect did not reach statistical significance for C-allele carriers (2.3 ± 6.8%; p = 0.33). Caffeine did not affect sprint time in the CODAT test in either genotype group but it increased the number of impacts performed during the simulated game in both AA homozygotes (4.1 ± 5.3%; p = 0.02) and C-allele carriers (3.3 ± 3.2%; p = 0.01). During the 24 h following the test, AA homozygotes tended to experience increased insomnia with caffeine while C-allele carriers did not present this effect. The remaining variables were unaffected by the genotype. Conclusion The CYP1A2 -163C>A polymorphism minimally altered the ergogenicity derived from the consumption of a moderate dose of caffeine in elite basketball players. PMID:29668752

The CYP1A2 -163C>A polymorphism does not alter the effects of caffeine on basketball performance.

Science.gov (United States)

Puente, Carlos; Abián-Vicén, Javier; Del Coso, Juan; Lara, Beatriz; Salinero, Juan José

2018-01-01

The aim of this investigation was to analyze the influence of the genetic variations of the -163C>A polymorphism of the CYP1A2 gene on the ergogenic effects of caffeine in elite basketball players. Nineteen elite basketball players (10 men and 9 women) ingested 3 mg⋅kg-1 of caffeine or a placebo 60 min before performing 10 repetitions of the following series: the Abalakov jump test followed by the Change-of-Direction and Acceleration Test (CODAT). The players then competed in a 20-min simulated basketball game. Self-perceived performance and side effects were recorded by questionnaires after the trials. The effects of caffeine on basketball performance were established according to players' CYP1A2 genotype (rs762551): AA homozygotes (n = 10) and C-allele carriers (n = 9). In the 10 repetitions, caffeine increased Abalakov jump height by a mean of 2.9±3.6% in AA homozygotes (p = 0.03) while this effect did not reach statistical significance for C-allele carriers (2.3 ± 6.8%; p = 0.33). Caffeine did not affect sprint time in the CODAT test in either genotype group but it increased the number of impacts performed during the simulated game in both AA homozygotes (4.1 ± 5.3%; p = 0.02) and C-allele carriers (3.3 ± 3.2%; p = 0.01). During the 24 h following the test, AA homozygotes tended to experience increased insomnia with caffeine while C-allele carriers did not present this effect. The remaining variables were unaffected by the genotype. The CYP1A2 -163C>A polymorphism minimally altered the ergogenicity derived from the consumption of a moderate dose of caffeine in elite basketball players.

Val103Ile polymorphism of the melanocortin-4 receptor gene (MC4R) in cancer cachexia

International Nuclear Information System (INIS)

Knoll, Susanne; Zimmer, Sabiene; Hinney, Anke; Scherag, André; Neubauer, Andreas; Hebebrand, Johannes

2008-01-01

At present pathogenic mechanisms of cancer cachexia are poorly understood. Previous evidence in animal models implicates the melanocortin-4 receptor gene (MC4R) in the development of cancer cachexia. In humans, MC4R mutations that lead to an impaired receptor function are associated with obesity; in contrast, the most frequent polymorphism (Val103Ile, rs2229616; heterozygote frequency approximately 2%) was shown to be negatively associated with obesity. We tested if cancer patients that are homo-/heterozygous for the Val103Ile polymorphism are more likely to develop cachexia and/or a loss of appetite than non-carriers of the 103Ile-allele. BMI (body mass index in kg/m 2 ) of 509 patients (295 males) with malignant neoplasms was determined; additionally patients were asked about premorbid/pretherapeutical changes of appetite and weight loss. Cachexia was defined as a weight loss of at least 5% prior to initiation of therapy; to fulfil this criterion this weight loss had to occur independently of other plausible reasons; in single cases weight loss was the initial reason for seeing a physician. The average age in years (± SD) was 59.0 ± 14.5 (males: 58.8 ± 14.0, females 59.2 ± 14.0). Blood samples were taken for genotyping of the Val103Ile by PCR- RFLP. Most of the patients suffered from lymphoma, leukaemia and gastrointestinal tumours. 107 of the patients (21%) fulfilled our criteria for cancer cachexia. We did not detect association between the Val103Ile polymorphism and cancer cachexia. However, if we exploratively excluded the patients with early leucaemic stages, we detected a trend towards the opposite effect (p < 0.05); heterozygotes for the 103Ile-allele developed cancer cachexia less frequently in comparison to the rest of the study group. Changes of appetite were not associated with the 103Ile-allele carrier status (p > 0.39). Heterozygotes for the 103Ile-allele are not more prone to develop cancer cachexia than patients without this allele; possibly

Val103Ile polymorphism of the melanocortin-4 receptor gene (MC4R) in cancer cachexia

Energy Technology Data Exchange (ETDEWEB)

Knoll, Susanne; Zimmer, Sabiene [Department of Child and Adolescent Psychiatry, University of Duisburg-Essen (Germany); Department of Hematology/Oncology/Immunology, University of Marburg (Germany); Hinney, Anke [Department of Child and Adolescent Psychiatry, University of Duisburg-Essen (Germany); Scherag, André [Zentrum for clinical studies food (ZKSE) c/o Institute for Medical Informatics, Biometry and Epidemiology, University Duisburg-Essen, Essen (Germany); Neubauer, Andreas [Department of Hematology/Oncology/Immunology, University of Marburg (Germany); Hebebrand, Johannes [Department of Child and Adolescent Psychiatry, University of Duisburg-Essen (Germany)

2008-03-31

At present pathogenic mechanisms of cancer cachexia are poorly understood. Previous evidence in animal models implicates the melanocortin-4 receptor gene (MC4R) in the development of cancer cachexia. In humans, MC4R mutations that lead to an impaired receptor function are associated with obesity; in contrast, the most frequent polymorphism (Val103Ile, rs2229616; heterozygote frequency approximately 2%) was shown to be negatively associated with obesity. We tested if cancer patients that are homo-/heterozygous for the Val103Ile polymorphism are more likely to develop cachexia and/or a loss of appetite than non-carriers of the 103Ile-allele. BMI (body mass index in kg/m{sup 2}) of 509 patients (295 males) with malignant neoplasms was determined; additionally patients were asked about premorbid/pretherapeutical changes of appetite and weight loss. Cachexia was defined as a weight loss of at least 5% prior to initiation of therapy; to fulfil this criterion this weight loss had to occur independently of other plausible reasons; in single cases weight loss was the initial reason for seeing a physician. The average age in years (± SD) was 59.0 ± 14.5 (males: 58.8 ± 14.0, females 59.2 ± 14.0). Blood samples were taken for genotyping of the Val103Ile by PCR- RFLP. Most of the patients suffered from lymphoma, leukaemia and gastrointestinal tumours. 107 of the patients (21%) fulfilled our criteria for cancer cachexia. We did not detect association between the Val103Ile polymorphism and cancer cachexia. However, if we exploratively excluded the patients with early leucaemic stages, we detected a trend towards the opposite effect (p < 0.05); heterozygotes for the 103Ile-allele developed cancer cachexia less frequently in comparison to the rest of the study group. Changes of appetite were not associated with the 103Ile-allele carrier status (p > 0.39). Heterozygotes for the 103Ile-allele are not more prone to develop cancer cachexia than patients without this allele

Specific Reaction Patterns to Distinct Positive Emotional Cues Related to Incentive Motivation in Dependence of the Taq1A-Polymorphism: Molecular Genetic Associations of Early and Late Event-Related Potentials.

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Munk, Aisha J L; Wielpuetz, Catrin; Osinsky, Roman; Müller, Erik M; Grant, Phillip; Hennig, Jürgen

2016-01-01

Early and late event-related potential (ERP) responses, representing early subconscious and late motivational processes, were recorded for positive emotional words related to 'wanting' and 'liking', in dependence of the dopamine-related Taq1A genotype (ANKK1/DRD2). Research suggests that 'wanting' as opposed to 'liking' is related to dopaminergic processes. Therefore, it was hypothesized that risk allele carriers of the Taq1A polymorphism exhibit late ERP changes in reaction to words representing incentive motivation, i.e. 'wanting' (word categories 'lust' and 'anticipation'), but not to words representing 'liking' ('closeness'). Seventy-two male participants performed an emotional-word Stroop task during EEG recording and were genotyped according to the Taq1A polymorphism of ANKK1/DRD2. Positive emotional words related to anticipation and lust revealed blunted responses in the late positive potential (LPP) in carriers of the A1 allele, an effect absent in response to 'liking'-related words. These differences were not evident in the earlier posterior negativity (EPN). As no differences in dependence of the Taq1A genotype were observed in reaction to 'wanting'- and 'liking'-related words in the EPN, but merely in the LPP, it can be assumed that incentive-motivational stimuli only modify motivation-related ERP responses in carriers of the A1 allele of the Taq1A polymorphism, indicating the role of dopamine in late ERP components. © 2016 S. Karger AG, Basel.

4G/5G polymorphism modulates PAI-1 circulating levels in obese women.

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Fernandes, Karla S; Sandrim, Valéria C

2012-05-01

The increase in plasminogen activator inhibitor type 1 (PAI-1) has been described as a risk factor to thrombosis-related diseases. In addition, it has been demonstrated that the variant 4G of polymorphism 4G/5G located in promoter region of PAI-1 gene is associated with higher PAI-1 levels. We investigate the role of this polymorphism on circulating PAI-1 concentration in a population of 57 obese women (23%, 4G/4G; 49%, 4G/5G and 28%, 5G/5G genotypes). Our results demonstrate a genotype-specific modulation on PAI-1 levels in obese women, thus 5G/5G genotype presented significantly lower levels of plasma PAI-1 when compared to 4G/4G group (46 ± 19 ng/mL vs. 63 ± 13 ng/mL, respectively). Our findings indicate that obese carriers of 4G/4G genotype may have increased risk to develop thrombotic diseases.

Polymorphism of the FABP2 gene: a population frequency analysis and an association study with cardiovascular risk markers in Argentina

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Mayorga Luis S

2007-06-01

Full Text Available Abstract Background The FABP2 gene encodes for the intestinal FABP (IFABP protein, which is expressed only in intestinal enterocytes. A polymorphism at codon 54 in exon 2 of the FABP2 gene exchanges an Alanine (Ala, in the small helical region of the protein, for Threonine (Thr. Given the potential physiological role of the Ala54Thr FABP2 polymorphism, we assess in this study the local population frequency and analyze possible associations with five selected markers, i.e. glycemia, total cholesterol, body mass index (BMI, hypertension, and high Cardiovascular Risk Index (CVR index. Methods We studied 86 men and 116 women. DNA was extracted from a blood drop for genotype analysis. Allele frequencies were calculated by direct counting. Hardy Weinberg Equilibrium was evaluated using a Chi-square goodness of fit test. For the polymorphism association analysis, five markers were selected, i.e. blood pressure, Framingham Risk Index, total cholesterol, BMI, and glycemia. For each marker, the Odds Ratio (OR was calculated by an online statistic tool. Results Our results reveal a similar population polymorphism frequency as in previous European studies, with q = 0.277 (95% confidence limits 0.234–0.323. No significant association was found with any of the tested markers in the context of our Argentine nutritional and cultural habits. We did, however, observe a tendency for increased Cholesterol and high BMI in Thr54 carriers. Conclusion This is the first study to look at the population frequency of the Thr54 allele in Argentina. The obtained result does not differ from previously reported frequencies in European populations. Moreover, we found no association between the Thr54 allele and any of the five selected markers. The observed tendency to increased total cholesterol and elevated BMI in Thr54 carriers, even though not significant for p

Brain-derived neurotrophic factor Val66Met polymorphism and hippocampal activation during episodic encoding and retrieval tasks

OpenAIRE

Dennis, Nancy A.; Cabeza, Roberto; Need, Anna C.; Waters-Metenier, Sheena; Goldstein, David B.; LaBar, Kevin S.

2010-01-01

Brain-derived neurotrophic factor (BDNF) is a neurotrophin which has been shown to regulate cell survival and proliferation, as well as synaptic growth and hippocampal long-term potentiation. A naturally occurring single nucleotide polymorphism in the human BDNF gene (val66met) has been associated with altered intercellular trafficking and regulated secretion of BDNF in met compared to val carriers. Additionally, previous studies have found a relationship between the BDNF val66met genotype an...

The relationship between XRCC1 and XRCC3 gene polymorphisms and lung cancer risk in northeastern Chinese.

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Shujie Guo

Full Text Available BACKGROUND: The prevalence of lung cancer in China will be the world's highest if allowed to proceed uncurbed. To unravel its genetic underpinnings, we sought to investigate the association of three well-characterized nonsynonymous polymorphisms in XRCC1 (Arg194Trp and Arg399Gln and XRCC3 (Thr241Met genes with lung cancer risk in northeastern Chinese. METHODOLOGY/PRINCIPAL FINDINGS: This study was hospital-based in design, encompassing 684 patients with lung cancer and 604 cancer-free controls. Genotyping was performed using the PCR-LDR (ligase detection reactions method. Data were analyzed by R language and multifactor dimensionality reduction (MDR software. Single-locus analysis identified significance in genotype distributions of polymorphism Arg194Trp (P = 0.002 and Arg399Gln (P = 0.017, and in allele distributions of Thr241Met (P = 0.005. Carriers of 399Gln/Gln genotype conferred a 147% increased risk relative to the non-carriers (odds ratio (OR: 2.47; 95% confidence interval (95% CI: 1.48-4.13; P<0.001. For Thr241Met, significance persisted under allelic (OR = 1.63; 95% CI: 1.14-2.33; P = 0.005, additive (OR = 1.64; 95% CI: 1.16-2.32; P = 0.005 and dominant (OR = 1.67; 95% CI: 1.17-2.38; P = 0.004 models. However, common allele combinations were comparable in frequency between patients and controls. In interaction analysis, the overall best MDR model included Arg399Gln and Thr241Met polymorphisms, with a maximal testing accuracy of 63.18% and a maximal cross-validation consistency of 10 out of 10 (P = 0.0175. CONCLUSIONS: Our study significantly demonstrated an independent and synergistic contribution of XRCC1 Arg399Gln and XRCC3 Thr241Met polymorphisms to lung cancer susceptibility in northeastern Chinese.

Association of XPC polymorphisms and lung cancer risk: a meta-analysis.

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Bo Jin

Full Text Available BACKGROUND: Xeroderma pigmentosum complementation group C gene (XPC is a key member of nucleotide excision repair pathway and plays an important role in human DNA repair system. It is reported that several common polymorphisms of XPC are associated with susceptibility to lung cancer. However, the conclusion is still elusive. METHOD: This meta-analysis was performed to determine the relationship between XPC polymorphisms (Lys939Gln, Ala499Val, and PAT and lung cancer risk. Published literatures were identified by searching online databases and reference lists of relevant studies. Odds ratios (ORs and 95% confidence intervals (CIs were calculated to estimate the association strength. Publication bias were detected by Egger's and Begg's test. RESULT: After strict screening, we identified 14 eligible studies in this meta-analysis, including 5647 lung cancer cases and 6908 controls. By pooling all eligible studies, we found that the homozygote Gln939Gln genotype was associated with a significantly increased risk of lung cancer in Asian population (GlnGln vs LysLys, OR=1.229, 95% CI: 1.000-1.510; GlnGln vs LysLys/LysGln, OR=1.257, 95% CI: 1.038-1.522. As for the PAT polymorphism, in Caucasian population, we found carriers of the -/- genotype were associated significantly reduced risk of lung cancer in homozygote comparison model (-/- vs +/+, OR=0.735, 95% CI: 0.567-0.952. CONCLUSION: In this meta-analysis we found that Gln939Gln genotype was associated with significantly increased risk of lung cancer in Asian population; the PAT -/- genotype significantly reduced susceptibility to lung cancer in Caucasian population; while the XPC Ala499Val polymorphism was not associated with lung cancer risk.

Severity of eating disorder symptoms related to oxytocin receptor polymorphisms in anorexia nervosa.

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Acevedo, Summer F; Valencia, Celeste; Lutter, Michael; McAdams, Carrie J

2015-08-30

Oxytocin is a peptide hormone important for social behavior and differences in psychological traits have been associated with variants of the oxytocin receptor gene in healthy people. We examined whether single nucleotide polymorphisms (SNPs) of the oxytocin receptor gene (OXTR) correlated with clinical symptoms in women with anorexia nervosa, bulimia nervosa, and healthy comparison (HC) women. Subjects completed clinical assessments and provided DNA for analysis. Subjects were divided into four groups: HC, subjects currently with anorexia nervosa (AN-C), subjects with a history of anorexia nervosa but in long-term weight recovery (AN-WR), and subjects with bulimia nervosa (BN). Five SNPs of the oxytocin receptor were examined. Minor allele carriers showed greater severity in most of the psychiatric symptoms. Importantly, the combination of having had anorexia and carrying either of the A alleles for two SNPS in the OXTR gene (rs53576, rs2254298) was associated with increased severity specifically for ED symptoms including cognitions and behaviors associated both with eating and appearance. A review of psychosocial data related to the OXTR polymorphisms examined is included in the discussion. OXTR polymorphisms may be a useful intermediate endophenotype to consider in the treatment of patients with anorexia nervosa. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

PTPN22 -1123G>C polymorphism and anti-cyclic citrullinated protein antibodies in rheumatoid arthritis.

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Muñoz-Valle, José Francisco; Padilla-Gutiérrez, Jorge Ramón; Hernández-Bello, Jorge; Ruiz-Noa, Yeniley; Valle, Yeminia; Palafox-Sánchez, Claudia Azucena; Parra-Rojas, Isela; Gutiérrez-Ureña, Sergio Ramón; Rangel-Villalobos, Hector

2017-08-10

The protein tyrosine phosphatase non-receptor type 22 (PTPN22) gene encodes an important negative regulator of T-cell activation, lymphoid-specific phosphatase -Lyp- and has been associated with different autoimmune disorders. The PTPN22 -1123G>C polymorphism appears to affect the transcriptional control of this gene, but to date, the biological significance of this polymorphisms on rheumatoid arthritis (RA) risk remains unknown. We evaluate the association of PTPN22 -1123G>C polymorphism with anti-cyclic citrullinated protein antibodies (anti-CCP) and risk for RA in population from Western Mexico. A transversal analytic study, which enrolled 300 RA patients classified according to ACR-EULAR criteria and 300 control subjects (CS) was conducted. The -1123 G>C polymorphism was genotyped by PCR-RFLP. The anti-CCP antibodies levels were quantified by ELISA kit. We found a higher prevalence of homozygous PTPN22 -1123CC genotype in CS than in RA patients (OR 0.41; 95% confidence interval 0.24-0.71; P=.001), suggesting a potential protective effect against RA. Concerning anti-CCP levels, the CC genotype carriers showed the lowest median levels in RA (P<.05). The PTPN22 -1123CC genotype is a protector factor to RA in a Mexican-mestizo population and is associated with low anti-CCP antibodies. Copyright © 2017 Elsevier España, S.L.U. All rights reserved.

Evaluation of the XRCC1 gene as a phenotypic modifier in BRCA1/2 mutation carriers. Results from the consortium of investigators of modifiers of BRCA1/BRCA2

NARCIS (Netherlands)

Osorio, A.; Milne, R. L.; Alonso, R.; Pita, G.; Peterlongo, P.; Teulé, A.; Nathanson, K. L.; Domchek, S. M.; Rebbeck, T.; Lasa, A.; Konstantopoulou, I.; Hogervorst, F. B.; Verhoef, S.; van Dooren, M. F.; Jager, A.; Ausems, M. G. E. M.; Aalfs, C. M.; van Asperen, C. J.; Vreeswijk, M.; Waisfisz, Q.; van Roozendaal, C. E.; Ligtenberg, M. J.; Easton, D. F.; Peock, S.; Cook, M.; Oliver, C. T.; Frost, D.; Curzon, B.; Evans, D. G.; Lalloo, F.; Eeles, R.; Izatt, L.; Davidson, R.; Adlard, J.; Eccles, D.; Ong, K.-r; Douglas, F.; Downing, S.; Brewer, C.; Walker, L.; Nevanlinna, H.; Aittomäki, K.; Couch, F. J.; Fredericksen, Z.; Lindor, N. M.; Godwin, A.; Isaacs, C.; Caligo, M. A.; Loman, N.; Jernström, H.; Barbany-Bustinza, G.; Liljegren, A.; Ehrencrona, H.; Stenmark-Askmalm, M.; Feliubadaló, L.; Manoukian, S.; Peissel, B.; Zaffaroni, D.; Bonanni, B.; Fortuzzi, S.; Johannsson, O. T.; Chenevix-Trench, G.; Chen, X.-C.; Beesley, J.; Spurdle, A. B.; Sinilnikova, O. M.; Healey, S.; McGuffog, L.; Antoniou, A. C.; Brunet, J.; Radice, P.; Benítez, J.; Hogervorst, F. B. L.; Verheus, M.; van 't Veer, L. J.; van Leeuwen, F. E.; Rookus, M. A.; Collée, M.; van den Ouweland, A. M. W.; Hooning, M. J.; Tilanus-Linthorst, M. M. A.; Seynaeve, C.; Wijnen, J. T.; Vreeswijk, M. P.; Tollenaar, R. A.; Devilee, P.; Hoogerbrugge, N.; Ausems, M. G.; van der Luijt, R. B.; van Os, T. A.; Gille, J. J. P.; Meijers-Heijboer, H. E. J.; Gomez-Garcia, E. B.; Blok, Marinus J.; Caanen, B.; Oosterwijk, J. C.; van der Hout, A. H.; Mourits, M. J.; Vasen, H. F.; Peock, Susan; Cook, Margaret; Oliver, Clare; Frost, Debra; Miedzybrodzka, Zosia; Gregory, Helen; Morrison, Patrick; Jeffers, Lisa; Cole, Trevor; McKeown, Carole; Ong, Kai-Ren; Hoffman, Jonathan; Donaldson, Alan; Paterson, Joan; Downing, Sarah; Taylor, Amy; Murray, Alexandra; Rogers, Mark T.; McCann, Emma; Kennedy, M. John; Barton, David; East, South; Porteous, Mary; Drummond, Sarah; Brewer, Carole; Kivuva, Emma; Searle, Anne; Goodman, Selina; Hill, Kathryn; Davidson, Rosemarie; Bradshaw, Nicola; Snadden, Lesley; Longmuir, Mark; Watt, Catherine; Gibson, Sarah; Izatt, Louise; Jacobs, Chris; Langman, Caroline; Whaite, Anna; Dorkins, Huw; Barwell, Julian; Adlard, Julian; Chu, Carol; Miller, Julie; Ellis, Ian; Evans, D. Gareth; Lalloo, Fiona; Taylor, Jane; Side, Lucy; Male, Alison; Berlin, Cheryl; Eason, Jacqueline; Collier, Rebecca; Douglas, Fiona; Claber, Oonagh; Walker, Lisa; McLeod, Diane; Halliday, Dorothy; Durell, Sarah; Stayner, Barbara; Eeles, Ros; Shanley, Susan; Rahman, Nazneen; Houlston, Richard; Bancroft, Elizabeth; D'Mello, Lucia; Page, Elizabeth; Ardern-Jones, Audrey; Kohut, Kelly; Wiggins, Jennifer; Castro, Elena; Mitra, Anitra; Robertson, Lisa; Cook, Jackie; Quarrell, Oliver; Bardsley, Cathryn; Hodgson, Shirley; Goff, Sheila; Brice, Glen; Winchester, Lizzie; Eddy, Charlotte; Tripathi, Vishakha; Attard, Virginia; Eccles, Diana; Lucassen, Anneke; Crawford, Gillian; McBride, Donna; Smalley, Sarah; Godwin, A. K.; Karlsson, Per; Nordling, Margareta; Bergman, Annika; Einbeigi, Zakaria; Stenmark- Askmalm, Marie; Liedgren, Sigrun; Borg, Ake; Loman, Niklas; Olsson, Håkan; Kristoffersson, Ulf; Jernström, Helena; Harbst, Katja; Henriksson, Karin; Lindblom, Annika; Arver, Brita; Wachenfeldt, Anna von; Liljegren, Annelie; Barbany-Bustinza, Gisela; Rantala, Johanna; Melin, Beatrice; Grönberg, Henrik; Stattin, Eva-Lena; Emanuelsson, Monica; Ehrencrona, Hans; Rosenquist Brandell, Richard; Dahl, Niklas

2011-01-01

Single-nucleotide polymorphisms (SNPs) in genes involved in DNA repair are good candidates to be tested as phenotypic modifiers for carriers of mutations in the high-risk susceptibility genes BRCA1 and BRCA2. The base excision repair (BER) pathway could be particularly interesting given the relation

Gender-specific association of ADA genetic polymorphism with human longevity.

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Napolioni, Valerio; Lucarini, Nazzareno

2010-08-01

Aim of this study was to investigate whether the polymorphic ADA (Adenosine Deaminase, EC 3.5.4.4) gene, which determines the cellular level of adenosine and plays a crucial role in the regulation of the immune system and in the control of metabolic rates, is involved in longevity. 884 unrelated healthy individuals (age range 10-106 years, 400 males and 484 females) from central Italy were studied. ADA genotyping was performed by RFLP-PCR. Frequency distributions were compared using the chi-square test and a three-way contingency table analysis by a log linear model was applied to test independence between the variables. We found that ADA influences human life-span in a sex and age specific way. An increased frequency of ADA*2 carriers was found in males aged 80-85, and a decreased frequency in males over 85 (chi(2) = 13.93; df = 3; P = 0.003); significant differences among the age groups was not found in females. A strong interaction among age groups, ADA genotype and sex (G = 15.086; df = 3; P = 0.0017) was found. Males aged 80-85 could be protected from ischemic stroke by higher levels of adenosine (determined by the ADA*2 allele). The decrease of ADA*2 carriers in males over 85 may depend essentially on immunological factors; reduced levels of adenosine protect from asthma and other pulmonary diseases and lead to a reduced activation of inflammatory cells and pro-inflammatory cytokines production. Moreover, the low level of adenosine may potentiate the activity of NK and other cellular effectors against tumor cells. The negligible effect of ADA genetic polymorphism in females suggest a marginal influence of genetic factors in determining longevity in this sex, confirming previous reports.

Inosine triphosphatase polymorphisms and ribavirin pharmacokinetics as determinants of ribavirin-associate anemia in patients receiving standard anti-HCV treatment.

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DʼAvolio, Antonio; Ciancio, Alessia; Siccardi, Marco; Smedile, Antonina; Baietto, Lorena; Simiele, Marco; Marucco, Diego Aguilar; Cariti, Giuseppe; Calcagno, Andrea; de Requena, Daniel Gonzalez; Sciandra, Mauro; Cusato, Jessica; Troshina, Giulia; Bonora, Stefano; Rizzetto, Mario; Di Perri, Giovanni

2012-04-01

Functional variants of inosine triphosphatase (ITPA) were recently found to protect against ribavirin (RBV)-induced hemolytic anemia. However, no definitive data are yet available on the role of plasma RBV concentrations on hemoglobin (Hb) decrement. Moreover, no data have been published on the possible interplay between these 2 factors. A retrospective analysis included 167 patients. The ITPA variants rs7270101 and rs1127354 were genotyped and tested using the χ test for association with Hb reduction at week 4. We also investigated, using multivariate logistic regression, the impact of RBV plasma exposure on Hb concentrations. Both single nucleotide polymorphisms were associated with Hb decrease. The carrier of at least 1 variant allele in the functional ITPA single nucleotide polymorphisms was associated with a lower decrement of Hb (-1.1 g/dL), as compared with patients without a variant allele (-2.75 g/dL; P = 4.09 × 10). RBV concentrations were not influenced by ITPA genotypes. A cut-off of 2.3 μg/mL of RBV was found to be associated with anemia (area-under-receiver operating characteristic = 0.630, sensitivity = 50.0%, and specificity = 69.5%, P = 0.008). In multivariate logistic regression analyses, the carrier of a variant allele (P = 0.005) and plasma RBV concentrations model based on ITPA genetic polymorphisms and RBV trough concentration was developed for predicting the risk of anemia. By relying upon these 2 variables, an individualized management of anemia seems to be feasible in recipients of pegylated interferon-RBV therapy.

Seasonal Changes in Brain Serotonin Transporter Binding in Short Serotonin Transporter Linked Polymorphic Region-Allele Carriers but Not in Long-Allele Homozygotes

DEFF Research Database (Denmark)

Kalbitzer, Jan; Erritzoe, David; Holst, Klaus K

2010-01-01

of the short 5-HTTLPR allele but not in homozygote carriers of the long allele. Conclusions: Our findings are in line with S-carriers having an increased response in neural circuits involved in emotional processing to stressful environmental stimuli but here demonstrated as a endophenotype with dynamic changes...

Modulation of trinucleotide repeat instability by DNA polymerase β polymorphic variant R137Q.

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Yaou Ren

Full Text Available Trinucleotide repeat (TNR instability is associated with human neurodegenerative diseases and cancer. Recent studies have pointed out that DNA base excision repair (BER mediated by DNA polymerase β (pol β plays a crucial role in governing somatic TNR instability in a damage-location dependent manner. It has been shown that the activities and function of BER enzymes and cofactors can be modulated by their polymorphic variations. This could alter the function of BER in regulating TNR instability. However, the roles of BER polymorphism in modulating TNR instability remain to be elucidated. A previous study has shown that a pol β polymorphic variant, polβR137Q is associated with cancer due to its impaired polymerase activity and its deficiency in interacting with a BER cofactor, proliferating cell nuclear antigen (PCNA. In this study, we have studied the effect of the pol βR137Q variant on TNR instability. We showed that pol βR137Q exhibited weak DNA synthesis activity to cause TNR deletion during BER. We demonstrated that similar to wild-type pol β, the weak DNA synthesis activity of pol βR137Q allowed it to skip over a small loop formed on the template strand, thereby facilitating TNR deletion during BER. Our results further suggest that carriers with pol βR137Q polymorphic variant may not exhibit an elevated risk of developing human diseases that are associated with TNR instability.

Polymorphisms in CISH gene are associated with persistent hepatitis B virus infection in Han Chinese population.

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Zhangyong Hu

Full Text Available BACKGROUND AND AIM: Cytokine-inducible SRC homology 2 domain protein (CISH is the first member of the suppressors of cytokine signaling (SOCS protein family. An association between multiple CISH polymorphisms and susceptibility to infectious diseases has been reported. This study aimed to investigate the possible association of these single nucleotide polymorphisms (SNPs in CISH gene with different outcomes of Hepatitis B virus (HBV infection. METHODS: 1019 unrelated Chinese Han subjects, including 240 persistent asymptomatic HBV carriers, 217 chronic hepatitis B patients, 137 HBV-related liver cirrhosis patients, and 425 cases of spontaneously recovered HBV as controls, were studied. Four SNPs (rs622502, rs2239751, rs414171 and rs6768300 in CISH gene were genotyped with the snapshot technique. Transcriptional activity of the CISH promoter was assayed in vitro using the dual-luciferase reporter assay system. RESULTS: At position rs414171, A allele and AA genotype frequencies were significantly higher in the HBV-resolved group as compared to the persistent HBV infection group. At position rs2239751, TT genotype was further observed in the HBV-resolved group. Using asymptomatic HBV carriers as controls, our results indicated that the rs414171 and rs2239751 polymorphisms were unrelated to HBV progression. The other two SNPs (rs622502 and rs6768300 showed no association with persistent HBV infection. Haplotype analysis revealed that the GGCA haplotype was associated with spontaneous clearance of HBV in this population. Moreover, luciferase activity was significantly higher in the PGL3-Basic-rs414171T construct as compared to the PGL3-Basic-rs414171A construct (p<0.001. CONCLUSION: Two SNPs (rs414171 and rs2239751 in the CISH gene were associated with persistent HBV infection in Han Chinese population, but not with HBV progression.

Family Polymorphism

DEFF Research Database (Denmark)

Ernst, Erik

2001-01-01

safety and flexibility at the level of multi-object systems. We are granted the flexibility of using different families of kinds of objects, and we are guaranteed the safety of the combination. This paper highlights the inability of traditional polymorphism to handle multiple objects, and presents family...... polymorphism as a way to overcome this problem. Family polymorphism has been implemented in the programming language gbeta, a generalized version of Beta, and the source code of this implementation is available under GPL....

Evaluation of Polygenic Risk Scores for Breast and Ovarian Cancer Risk Prediction in BRCA1 and BRCA2 Mutation Carriers

DEFF Research Database (Denmark)

Kuchenbaecker, Karoline B; McGuffog, Lesley; Barrowdale, Daniel

2017-01-01

Background: Genome-wide association studies (GWAS) have identified 94 common single-nucleotide polymorphisms (SNPs) associated with breast cancer (BC) risk and 18 associated with ovarian cancer (OC) risk. Several of these are also associated with risk of BC or OC for women who carry a pathogenic ...... risk in BRCA1 and BRCA2 carriers. Incorporation of the PRS into risk prediction models has promise to better inform decisions on cancer risk management....

Transient receptor potential melastatin 8 gene polymorphism is associated with cold-induced airway hyperresponsiveness in bronchial asthma.

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Naumov, Denis E; Perelman, Juliy M; Kolosov, Victor P; Potapova, Tatyana A; Maksimov, Vladimir N; Zhou, Xiangdong

2015-11-01

Cold-induced airway hyperresponsiveness (CAH) is common in bronchial asthma (BA) patients and represents a problem for those living in cold climate. Transient receptor potential melastatin 8 (TRPM8) channel is the main cold temperature sensor in humans that could mediate cold response in asthmatics with CAH. No associations between TRPM8 gene polymorphisms and CAH have been reported. The present study involved 123 BA patients. CAH was assessed by 3-min isocapnic (5% CO2 ) cold air (-20°C) hyperventilation challenge. The c.750G > C (rs11562975), c.1256G > A (rs7593557), c.3048C > T (rs11563208) and c.3174C > G (rs11563071) polymorphisms of TRPM8 gene were genotyped by allele-specific polymerase chain reaction (PCR) and PCR with subsequent restriction fragment length polymorphism analysis. GC genotype and C allele carriers of the c.750G > C (rs11562975) polymorphism were more frequently observed to exhibit CAH. The estimated odds ratio for the GC genotype was 3.73 95%CI (1.48; 9.37), P = 0.005. Furthermore, GC heterozygotes had a prominent decrease in forced expiratory volume in 1 s after the challenge as compared to GG homozygotes (-12% (-16; -8.1) vs -6.45% (-11; -2.1), P  C (rs11562975) polymorphism is associated with CAH in patients with BA, which suggests a potential role of TRPM8 in CAH development. © 2015 Asian Pacific Society of Respirology.

Polymorphous computing fabric

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Wolinski, Christophe Czeslaw [Los Alamos, NM; Gokhale, Maya B [Los Alamos, NM; McCabe, Kevin Peter [Los Alamos, NM

2011-01-18

Fabric-based computing systems and methods are disclosed. A fabric-based computing system can include a polymorphous computing fabric that can be customized on a per application basis and a host processor in communication with said polymorphous computing fabric. The polymorphous computing fabric includes a cellular architecture that can be highly parameterized to enable a customized synthesis of fabric instances for a variety of enhanced application performances thereof. A global memory concept can also be included that provides the host processor random access to all variables and instructions associated with the polymorphous computing fabric.

Effects of polymorphisms in ERCC1, ASE-1 and RAI on the risk of colorectal carcinomas and adenomas: a case control study

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Wallin Håkan

2006-07-01

Full Text Available Abstract Background The risk of sporadic colorectal cancer is mainly associated with lifestyle factors and may be modulated by several genetic factors of low penetrance. Genetic variants represented by single nucleotide polymorphisms in genes encoding key players in the adenoma carcinoma sequence may contribute to variation in susceptibility to colorectal cancer. In this study, we aimed to evaluate whether the recently identified haplotype encompassing genes of DNA repair and apoptosis, is associated with increased risk of colorectal adenomas and carcinomas. Methods We used a case-control study design (156 carcinomas, 981 adenomas and 399 controls to test the association between polymorphisms in the chromosomal region 19q13.2-3, encompassing the genes ERCC1, ASE-1 and RAI, and risk of colorectal adenomas and carcinomas in a Norwegian cohort. Odds ratio (OR and 95% confidence interval (CI were estimated by binary logistic regression model adjusting for age and gender. Results The ASE-1 polymorphism was associated with an increased risk of adenomas, OR of 1.39 (95% CI 1.06–1.81, which upon stratification was apparent among women only, OR of 1.66 (95% CI 1.15–2.39. The RAI polymorphism showed a trend towards risk reduction for both adenomas (OR of 0.70, 95% CI 0.49–1.01 and carcinomas (OR of 0.49, 95% CI 0.21–1.13 among women, although not significant. Women who were homozygous carriers of the high risk haplotype had an increased risk of colorectal cancer, OR of 2.19 (95% CI 0.95–5.04 compared to all non-carriers although the estimate was not statistically significant. Conclusion We found no evidence that the studied polymorphisms were associated with risk of adenomas or colorectal cancer among men, but we found weak indications that the chromosomal region may influence risk of colorectal cancer and adenoma development in women.

Revisited the relationship between vitamin D level and receptors of BsmI- gene polymorphism with the pathogenetic mechanisms of placental dysfunction development

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G. S. Manasova

2018-03-01

Full Text Available The role of the calcitriol / vitamin D receptor (VD endocrine system and the pleiotropic effects of this system in the pathogenetic mechanisms of various diseases development, in particular complications of pregnancy, has attracted researches’ increasing attention in recent years. The aim of the work: to compare the VD-status and frequency of occurrence of polymorphism of the VDR gene (BsmI (A> G, rs1544410 in patients with a physiological course of the gestation process and in patients with placental dysfunction (PD. Materials and methods. 56 pregnant women with PD (the main group and 40 patients with a physiological pregnancy (control group were examined. VD status was determined by ELISA at level 25 (OH D in serum, the frequency of BsmI polymorphism of the VDR gene (rs1544410 by polymerase chain reaction (PCR. Results. The average index of VD (31.40 ± 8.6 ng / ml in patients with PD is significantly lower than in patients with physiological pregnancy (43.54 ± 11.20 ng / ml, (p ≤ 0.05 . In patients with PD, homozygous carrier for the A-allele was found in 12% of cases, in healthy pregnant women - in 16.7%, (р ≥ 0.05, for the G-allele - in 20% and 47.20%, (р ≤ 0.01 cases, respectively to groups. Heterozygous combination of A / G alleles was noted in 68% of patients with PD and in 36.10% of the control group patients. In pregnant women with BsmI polymorphism of calcitriol gene (genotype A / G PD was 3.7 times more frequent (68% vs 36.10% : RR = 2.1, CI 1.0-6.6, OR = 3.7, CI 1.1-13.1. Conclusions. Vitamin D insufficiency or deficiency can be one of the reasons of PD formation. In carriers of BsmIgene’s polymorphism encoding VD receptor with genotype A / G, the course of pregnancy is complicated by placental dysfunction 3.7 times more often than in women without this polymorphism.

Distribution of genotypes C825T polymorphism G-protein β3-subunit gene in patients with hypertension depending on body mass index

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Prystupa L.N.

2015-09-01

Full Text Available The aim of the study was to investigate the frequency of genotypes of C825T polymorphism G-protein β3-subunit gene (GNB3 in patients with arterial hypertension (AH, depending on body mass index (BMI. The study involved 155 patients with verified diagnosis of AH (study group and 50 healthy individuals (control group. The patients of the main group were divided into 3 groups according to BMI: I - 35 patients with normal body weight, II - 38 patients with overweight, III - 82 patients with obesity. We used general clinical, anthropometric, instrumental, molecular-genetic and statistical methods. Probability of differences in the frequency of alleles and genotypes was determined using χ² criteria. Pairwise comparison of groups was made using nonparametric Mann-Whitney test. The difference was considered statistically significant at p <0,05. Investigation of the distribution of genotypes C825T polymorphism GNB3 in patients with AH according to BMI showed statistically significant increase in the frequency of genotypes C / T and T / T and T allele in patients with overweight and obesity as compared with patients with normal body weight (χ² = 26 8; p <0.001. The risk of weight increase in AH patients with T allele carriers is 2,2 times higher than in C allele carriers. Association of C825T polymorphism of GNB3 with a tendency to obesity and overweight in patients with AH was proved.

Polymorphisms of the Kappa Opioid Receptor and Prodynorphin Genes: HIV risk and HIV Natural History

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Proudnikov, Dmitri; Randesi, Matthew; Levran, Orna; Yuferov, Vadim; Crystal, Howard; Ho, Ann; Ott, Jurg; Kreek, Mary Jeanne

2013-01-01

Objective Studies indicate cross-desensitization between opioid receptors (e.g., kappa opioid receptor, OPRK1), and chemokine receptors (e.g., CXCR4) involved in HIV infection. We tested whether gene variants of OPRK1 and its ligand, prodynorphin (PDYN), influence the outcome of HIV therapy. Methods Three study points, admission to the Women’s Interagency HIV Study (WIHS), initiation of highly active antiretroviral therapy (HAART) and the most recent visit were chosen for analysis as crucial events in the clinical history of the HIV patients. Regression analyses of 17 variants of OPRK1, and 11 variants of PDYN with change of viral load (VL) and CD4 count between admission and initiation of HAART, and initiation of HAART to the most recent visit to WIHS were performed in 598 HIV+ subjects including African Americans, Hispanics and Caucasians. Association with HIV status was done in 1009 subjects. Results Before HAART, greater VL decline (improvement) in carriers of PDYN IVS3+189C>T, and greater increase of CD4 count (improvement) in carriers of OPRK1 −72C>T, were found in African Americans. Also, greater increase of CD4 count in carriers of OPRK1 IVS2+7886A>G, and greater decline of CD4 count (deterioration) in carriers of OPRK1 −1205G>A, were found in Caucasians. After HAART, greater decline of VL in carriers of OPRK1 IVS2+2225G>A, and greater increase of VL in carriers of OPRK1 IVS2+10658G>T and IVS2+10963A>G, were found in Caucasians. Also, a lesser increase of CD4 count was found in Hispanic carriers of OPRK1 IVS2+2225G>A. Conclusion OPRK1 and PDYN polymorphisms may alter severity of HIV infection and response to treatment. PMID:23392455

Social memory associated with estrogen receptor polymorphisms in women

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Karlsson, Sara; Henningsson, Susanne; Hovey, Daniel; Zettergren, Anna; Jonsson, Lina; Cortes, Diana S.; Melke, Jonas; Laukka, Petri; Fischer, Håkan

2016-01-01

The ability to recognize the identity of faces and voices is essential for social relationships. Although the heritability of social memory is high, knowledge about the contributing genes is sparse. Since sex differences and rodent studies support an influence of estrogens and androgens on social memory, polymorphisms in the estrogen and androgen receptor genes (ESR1, ESR2, AR) are candidates for this trait. Recognition of faces and vocal sounds, separately and combined, was investigated in 490 subjects, genotyped for 10 single nucleotide polymorphisms (SNPs) in ESR1, four in ESR2 and one in the AR. Four of the associations survived correction for multiple testing: women carrying rare alleles of the three ESR2 SNPs, rs928554, rs1271572 and rs1256030, in linkage disequilibrium with each other, displayed superior face recognition compared with non-carriers. Furthermore, the uncommon genotype of the ESR1 SNP rs2504063 was associated with better recognition of identity through vocal sounds, also specifically in women. This study demonstrates evidence for associations in women between face recognition and variation in ESR2, and recognition of identity through vocal sounds and variation in ESR1. These results suggest that estrogen receptors may regulate social memory function in humans, in line with what has previously been established in mice. PMID:26955855

Is PPARα intron 7 G/C polymorphism associated with muscle strength characteristics in nonathletic young men?

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Broos, S; Windelinckx, A; De Mars, G; Huygens, W; Peeters, M W; Aerssens, J; Vlietinck, R; Beunen, G P; Thomis, M A

2013-08-01

Peroxisome proliferator-activated receptor alpha (PPARα), a ligand-dependent transcription factor, regulates fatty acid metabolism in heart and skeletal muscle. The intron 7 G/C polymorphism (rs4253778) has been associated with athletic performance. The rare C-allele was predominant in power athletes, whereas the G-allele was more frequent in endurance athletes. In the present study, we investigated the association between this polymorphism and strength characteristics in nonathletic, healthy young adults (n = 500; age 24.2 ± 4.4 years). Knee torque was measured during concentric knee flexion and extension movements at 60°/s, 120°/s, and 240°/s during 3, 25, and 5 repetitions, respectively. Also, resistance to muscle fatigue (i.e. work last 20% repetitions/work first 20% repetitions *100) was calculated. Differences in knee strength phenotypes between GG homozygous individuals and C-allele carriers were analyzed. The polymorphism did not influence the ability to produce isometric or dynamic knee flexor or extensor peak torque during static or dynamic conditions in this population (0.23 < P < 0.95). Similar results were found for the endurance ratio, a measure for resistance to muscle fatigue. In conclusion, the PPARα intron 7 G/C polymorphism does not seem to influence strength characteristics in a nonathletic population. © 2011 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

PlA polymorphism and platelet reactivity following clopidogrel loading dose in patients undergoing coronary stent implantation.

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Angiolillo, Dominick J; Fernandez-Ortiz, Antonio; Bernardo, Esther; Alfonso, Fernando; Sabaté, Manel; Fernández, Cristina; Stranieri, Chiara; Trabetti, Elisabetta; Pignatti, Pier Franco; Macaya, Carlos

2004-01-01

The PlA polymorphism (Leu33Pro) of the platelet glycoprotein (GP) IIIa gene has been suggested to play an important role in coronary thrombosis. In vitro studies have shown differences for this polymorphism in platelet sensitivity towards antiplatelet drugs (aspirin and abciximab), suggesting a pharmacogenetic modulation. The aim of the study was to assess the modulatory effect of the PlA polymorphism on clopidogrel-induced antiplatelet effects in 38 patients undergoing coronary stent implantation receiving a 300 mg clopidogrel loading-dose. Platelet reactivity was assessed as GPIIb/IIIa activation and P-selectin expression in platelets stimulated with 2 micromol/l adenosine diphosphate using whole blood flow cytometry. The distribution of the homozygous PlA1/A1 and heterozygous PlA1/A2 genotypes were 74 and 26%, respectively. PlA2 carriers had a higher degree of GPIIb/IIIa activation (P = 0.05) and P-selectin expression (P = 0.02) during the overall study time course and a lower antiplatelet effect to a 300 mg clopidogrel loading-dose up to 24 h following intervention (P < 0.05). In conclusion, the Pl polymorphism of the GPIIIa gene modulates platelet reactivity towards clopidogrel front loading in patients undergoing coronary stenting. This suggests the need for individualized antithrombotic regimens to optimally inhibit platelet reactivity. Copyright 2004 Lippincott Williams and Wilkins

Polymorphisms in STAT4 and IRF5 increase the risk of systemic sclerosis: a meta-analysis.

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Xu, Yang; Wang, Wenling; Tian, Yanli; Liu, Jingyang; Yang, Rongya

2016-04-01

Systemic sclerosis (SSc) is the most severe connective tissue disorder. Recent studies have demonstrated that genetic factors may play a role in the development of SSc. The aim of this study was to investigate the association of signal transducer and activator of transcription 4 (STAT4) rs7574865 and interferon regulatory factor 5 (IRF5) rs2004640 polymorphisms with risk of SSc. Case-control studies were obtained from the electronic database of PubMed, Medline, Embase, and CNKI (China National Knowledge Infrastructure) up to December 2013. The association between STAT4 and IRF5 polymorphisms and SSc susceptibility was assessed by pooled odds ratios (ORs) and 95% confidence intervals (CI). Six related studies, including 4746 SSc cases and 7399 healthy controls, were pooled in this meta-analysis. For STAT4 polymorphism, we observed a statistically significant positive association between risk factor T allele carriers and SSc susceptibility (OR = 1.37, 95% CI = 1.27-1.48, P rs7574865 and IRF5 rs2004640G/T substitution are associated with a susceptibility to SSc, and they may serve as the SSc genetic susceptibility factor. These data confirmed that genetic polymorphisms may play a role in the development of SSc and have provided new insight into the pathogenesis of SSc. © 2015 The International Society of Dermatology.

Polymorphisms within the neuronal cadherin (CDH2) gene are associated with obsessive-compulsive disorder (OCD) in a South African cohort.

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McGregor, N W; Lochner, C; Stein, D J; Hemmings, S M J

2016-02-01

OCD is characterised by recurrent obsessions and compulsions that result in severe distress and increased risk for comorbidity. Recently published findings have indicated that the neuronal cadherin gene (CDH2) plays a role in the development of canine OCD, and led us to investigate the human ortholog, CDH2, in a human OCD cohort. Seven CDH2 polymorphisms were selected and genotyped in a South African Caucasian cohort of 234 OCD patients and 180 healthy controls using TaqMan assays. Polymorphisms were analysed in a single-locus and haplotypic context. Of the seven polymorphisms, two reached statistical significance for OCD under additive and codominant models of inheritance (rs1120154 and rs12605662). CDH2 SNP, rs1120154, C-allele carriers were found to be significantly associated with lower risk to develop OCD compared to TT-homozygotes (OR = 0.49; 95% CI: 0.32-0.75; p OCD compared to TT-homozygotes (OR = 0.46; 95% CI: 0.30-0.71; p OCD diagnosis (*rs8087457-rs1148374: A-T). Polymorphisms within the CDH2 gene are associated with susceptibility to OCD in a South African cohort.

The thrombospondin-1 N700S polymorphism is associated with early myocardial infarction without altering von Willebrand factor multimer size.

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Zwicker, Jeffrey I; Peyvandi, Flora; Palla, Roberta; Lombardi, Rossana; Canciani, Maria Teresa; Cairo, Andrea; Ardissino, Diego; Bernardinelli, Luisa; Bauer, Kenneth A; Lawler, Jack; Mannucci, Pier

2006-08-15

The N700S polymorphism of thrombospondin-1 (TSP-1) has been identified as a potential genetic risk factor for myocardial infarction (MI). In a large case-control study of 1425 individuals who survived a myocardial infarction prior to age 45, the N700S polymorphism was a significant risk factor for myocardial infarction in both homozygous (odds ratio [OR] 1.9, 95% confidence interval [CI] 1.1-3.3, P = .01) and heterozygous carriers of the S700 allele (OR 1.4, 95% CI 1.1-3.3, P = .01). TSP-1 has been shown to reduce von Willebrand factor (VWF) multimer size, and the domain responsible for VWF-reducing activity has been localized to the calcium-binding C-terminal sequence. As the N700S polymorphism was previously shown to alter the function of this domain, we investigated whether the altered VWF-reducing activity of TSP-1 underlies the observed prothrombotic phenotype. The TSP1 N700S polymorphism did not influence VWF multimer size in patients homozygous for either allele nor was there a significant reduction of VWF multimer size following incubation with recombinant N700S fragments or platelet-derived TSP-1.

Identification of Human T-lymphotropic Virus Type I (HTLV-I Subtypes Using Restrited Fragment Length Polymorphism in a Cohort of Asymptomatic Carriers and Patients with HTLV-I-associated Myelopathy/tropical Spastic Paraparesis from São Paulo, Brazil

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Segurado Aluisio AC

2002-01-01

Full Text Available Although human T-lymphotropic virus type I (HTLV-I exhibits high genetic stability, as compared to other RNA viruses and particularly to human immunodeficiency virus (HIV, genotypic subtypes of this human retrovirus have been characterized in isolates from diverse geographical areas. These are currently believed not to be associated with different pathogenetic outcomes of infection. The present study aimed at characterizing genotypic subtypes of viral isolates from 70 HTLV-I-infected individuals from São Paulo, Brazil, including 42 asymptomatic carriers and 28 patients with HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP, using restricted fragment length polymorphism (RFLP analysis of long terminal repeat (LTR HTLV-I proviral DNA sequences. Peripheral blood mononuclear cell lysates were amplified by nested polymerase chain reaction (PCR and amplicons submitted to enzymatic digestion using a panel of endonucleases. Among HTLV-I asymptomatic carriers, viral cosmopolitan subtypes A, B, C and E were identified in 73.8%, 7.1%, 7.1% and 12% of tested samples, respectively, whereas among HAM/TSP patients, cosmopolitan A (89.3%, cosmopolitan C (7.1% and cosmopolitan E (3.6% subtypes were detected. HTLV-I subtypes were not statistically significant associated with patients' clinical status. We also conclude that RFLP analysis is a suitable tool for descriptive studies on the molecular epidemiology of HTLV-I infections in our environment.

Low-complexity Joint Sub-carrier Phase Noise Compensation for Digital Multi-carrier Systems

DEFF Research Database (Denmark)

Yankov, Metodi Plamenov; Barletta, Luca; Zibar, Darko

2017-01-01

Joint sub-carrier phase noise processing is proposed which recovers the SNR penalty related to decreased sub-carrier baudrate w.r.t. single carrier systems. The method enables digital sub-banding to be safely employed for nonlinear mitigation for modulation formats of up to 256-QAM.......Joint sub-carrier phase noise processing is proposed which recovers the SNR penalty related to decreased sub-carrier baudrate w.r.t. single carrier systems. The method enables digital sub-banding to be safely employed for nonlinear mitigation for modulation formats of up to 256-QAM....

No association of the BDNF val66met polymorphism with implicit associative vocabulary and motor learning.

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Nils Freundlieb

Full Text Available Brain-derived neurotrophic factor (BDNF has been suggested to play a major role in plasticity, neurogenesis and learning in the adult brain. The BDNF gene contains a common val66met polymorphism associated with decreased activity-dependent excretion of BDNF and a potential influence on behaviour, more specifically, on motor learning. The objective of this study was to determine the influence of the BDNF val66met polymorphism on short-term implicit associative learning and whether its influence is cognitive domain-specific (motor vs. language. A sample of 38 young healthy participants was genotyped, screened for background and neuropsychological differences, and tested with two associative implicit learning paradigms in two different cognitive domains, i.e., motor and vocabulary learning. Subjects performed the serial reaction time task (SRTT to determine implicit motor learning and a recently established associative vocabulary learning task (AVL for implicit learning of action and object words. To determine the influence of the BDNF polymorphism on domain-specific implicit learning, behavioural improvements in the two tasks were compared between val/val (n = 22 and met carriers (val/met: n = 15 and met/met: n = 1. There was no evidence for an impact of the BDNF val66met polymorphism on the behavioural outcome in implicit short-term learning paradigms in young healthy subjects. Whether this polymorphism plays a relevant role in long-term training paradigms or in subjects with impaired neuronal plasticity or reduced learning capacity, such as aged individuals, demented patients or patients with brain lesions, has to be determined in future studies.

Carrier-interleaved orthogonal multi-electrode multi-carrier resistivity-measurement tool

International Nuclear Information System (INIS)

Cai, Yu; Sha, Shuang

2016-01-01

This paper proposes a new carrier-interleaved orthogonal multi-electrode multi-carrier resistivity-measurement tool used in a cylindrical borehole environment during oil-based mud drilling processes. The new tool is an orthogonal frequency division multiplexing access-based contactless multi-measurand detection tool. The tool can measure formation resistivity in different azimuthal angles and elevational depths. It can measure many more measurands simultaneously in a specified bandwidth than the legacy frequency division multiplexing multi-measurand tool without a channel-select filter while avoiding inter-carrier interference. The paper also shows that formation resistivity is not sensitive to frequency in certain frequency bands. The average resistivity collected from N subcarriers can increase the measurement of the signal-to-noise ratio (SNR) by N times given no amplitude clipping in the current-injection electrode. If the clipping limit is taken into account, with the phase rotation of each single carrier, the amplitude peak-to-average ratio can be reduced by 3 times, and the SNR can achieve a 9/ N times gain over the single-carrier system. The carrier-interleaving technique is also introduced to counter the carrier frequency offset (CFO) effect, where the CFO will cause inter-pad interference. A qualitative analysis and simulations demonstrate that block-interleaving performs better than tone-interleaving when coping with a large CFO. The theoretical analysis also suggests that increasing the subcarrier number can increase the measurement speed or enhance elevational resolution without sacrificing receiver performance. The complex orthogonal multi-pad multi-carrier resistivity logging tool, in which all subcarriers are complex signals, can provide a larger available subcarrier pool than other types of transceivers. (paper)

Association of CTLA-4 gene polymorphisms with sporadic breast cancer in Chinese Han population

International Nuclear Information System (INIS)

Wang, Lihong; Li, Dalin; Fu, Zhenkun; Li, Heng; Jiang, Wei; Li, Dianjun

2007-01-01

The host immunogenetic background plays an important role in the development of breast cancer. Cytotoxic T-lymphocyte antigen-4 (CTLA-4) is a molecule expressed predominantly on activated T cells and is important during the down-regulation of T-cell activation. To evaluate the potential influences of CTLA-4 gene polymorphisms on breast cancer risk, a case-control study was conducted in Han women of Northeast China. We genotyped CTLA-4 variants (-1661 G/A, -658 T/C, -318 T/C, +49 G/A and CT60 G/A) to tag all common haplotypes (≥ 1% frequency) in 117 Chinese breast cancer cases and 148 age/sex matched healthy individuals. Genotypes were determined by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Data was analyzed using the Chi-square test and Haploview software. The frequency of CTLA-4 -1661G allele, -318T allele and CT60G allele carriers was significantly higher in patients than in controls (P = 0.0057, OR 1.91, 95% CI 1.21–3.02; P = 0.0031, OR 2.39, 95% CI 1.34–4.27; P = 0.023, OR 1.52, 95% CI 1.06–2.17, respectively). The -658T allele carrier frequency was significantly lower than in controls (P = 0.0000082, OR 0.17, 95% CI 0.08–0.37), whereas the +49A allele was significantly associated with tumor size in patients (P = 0.0033). Two common CTLA-4 haplotypes, ATCGA and ATCAG, were higher in healthy controls than patients (P = 0.0026, OR 0.17, 95% CI 0.05–0.54; P = 0.034, OR 0.12, 95% CI 0.02–0.92, respectively). A strong association was observed between tumor size and the ACCAA, ACCAG and ACCGA haplotypes (P = 0.0032, P = 0.0000031 and P = 0.017). These results suggest that polymorphisms of the CTLA-4 gene may modify individual susceptibility to and progression of breast cancer in Chinese Han women

Association between polymorphisms in selected inflammatory response genes and the risk of prostate cancer

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Chen J

2016-01-01

Full Text Available Jun Chen,1,* Xue-Ming Ying,2,* Xue-Ming Huang,3 Peng Huang,4 Shao-Cong Yan1 1Department of Oncology, The First Affiliated Hospital of Nanchang University, Nanchang, 2Department of Oncology, Jingdezhen City People’s Hospital, Jingdezhen, 3Department of Urology, Research Institute, The First Affiliated Hospital of Nanchang University, 4The Medical School of Nanchang University, School of Public Health, Nanchang, People’s Republic of China*These authors contributed equally to this workAbstract: Inflammation represents an important event which facilitates prostate carcinogenesis. Genetic variations in inflammatory response genes could affect the level and function of the protein products, resulting in the differential prostate cancer risk among carriers of different variants. This study attempted to investigate the association of IL-4 rs2243250, IL-6 rs10499563, IL-8 rs4073, as well as NFKBIA rs2233406 and rs3138053 polymorphisms with prostate cancer risk in the Chinese population. Genotyping of the polymorphisms was performed by using polymerase chain reaction-restriction fragment length polymorphism technique on 439 prostate cancer patients and 524 controls, and the association of each polymorphic genotype with prostate cancer risk was evaluated by using logistic regression analysis based on allele, heterozygous, and homozygous comparison models, with adjustment to age and smoking status. We showed that the C allele of IL-4 rs2243250 polymorphism could increase prostate cancer risk (heterozygous comparison model: odds ratio [OR] =1.434, 95% confidence interval [CI] =1.092–1.881, P=0.009; homozygous comparison model: OR =2.301, 95% CI =1.402–3.775, P=0.001; allele comparison model: OR =1.509, 95% CI =1.228–1.853, P<0.001. On the other hand, the C allele of rs10499563 polymorphism could decrease prostate cancer risk (heterozygous comparison model: OR =0.694, 95% CI =0.525–0.918, P=0.010; homozygous comparison model: OR =0.499, 95% CI =0

Polymorphisms in metabolism and repair genes affects DNA damage caused by open-cast coal mining exposure.

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Espitia-Pérez, Lyda; Sosa, Milton Quintana; Salcedo-Arteaga, Shirley; León-Mejía, Grethel; Hoyos-Giraldo, Luz Stella; Brango, Hugo; Kvitko, Katia; da Silva, Juliana; Henriques, João A P

2016-09-15

Increasing evidence suggest that occupational exposure to open-cast coal mining residues like dust particles, heavy metals and Polycyclic Aromatic Hydrocarbons (PAHs) may cause a wide range of DNA damage and genomic instability that could be associated to initial steps in cancer development and other work-related diseases. The aim of our study was to evaluate if key polymorphisms in metabolism genes CYP1A1Msp1, GSTM1Null, GSTT1Null and DNA repair genes XRCC1Arg194Trp and hOGG1Ser326Cys could modify individual susceptibility to adverse coal exposure effects, considering the DNA damage (Comet assay) and micronucleus formation in lymphocytes (CBMN) and buccal mucosa cells (BMNCyt) as endpoints for genotoxicity. The study population is comprised of 200 healthy male subjects, 100 open-cast coal-mining workers from "El Cerrejón" (world's largest open-cast coal mine located in Guajira - Colombia) and 100 non-exposed referents from general population. The data revealed a significant increase of CBMN frequency in peripheral lymphocytes of occupationally exposed workers carrying the wild-type variant of GSTT1 (+) gene. Exposed subjects carrying GSTT1null polymorphism showed a lower micronucleus frequency compared with their positive counterparts (FR: 0.83; P=0.04), while BMNCyt, frequency and Comet assay parameters in lymphocytes: Damage Index (DI) and percentage of DNA in the tail (Tail % DNA) were significantly higher in exposed workers with the GSTM1Null polymorphism. Other exfoliated buccal mucosa abnormalities related to cell death (Karyorrhexis and Karyolysis) were increased in GSTT/M1Null carriers. Nuclear buds were significantly higher in workers carrying the CYP1A1Msp1 (m1/m2, m2/m2) allele. Moreover, BMNCyt frequency and Comet assay parameters were significantly lower in exposed carriers of XRCC1Arg194Trp (Arg/Trp, Trp/Trp) and hOGG1Ser326Cys (Ser/Cys, Cys/Cys), thereby providing new data to the increasing evidence about the protective role of these polymorphisms

Interaction between interleukin-10 (IL-10 polymorphisms and dietary fibre in relation to risk of colorectal cancer in a Danish case-cohort study

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Andersen Vibeke

2012-05-01

Full Text Available Abstract Background More than 50% of the colorectal cancer (CRC etiology has been attributed to diet. Established or suspected dietary factors modifying risk of CRC are red meat, cereals, fish, and fibre. Diet and lifestyle may be linked to cancer through inflammation. Interleukin-10 (IL-10 is an anti-inflammatory cytokine. We wanted to test if dietary factors and IL10 polymorphisms interact in relation to colorectal carcinogenesis. Methods The functional IL10 polymorphism C-592A (rs1800872 and the marker rs3024505 were assessed in relation to diet and lifestyle in a nested case-cohort study of 378 CRC cases and 775 randomly selected participants from a prospective study of 57,053 persons. Genotyping data on the IL10 polymorphism C-592A, smoking and non-steroidal anti-inflammatory drugs (NSAID was retrieved from Vogel et al. (Mutat Res, 2007; 624:88. Incidence rate ratios (IRR and 95% Confidence Interval (95% CI were calculated. Results No associations were found between the IL10 rs3024505 polymorphism and risk of CRC. There was interaction between rs3024505 and dietary fibre (P-value for interaction = 0.01. IL10 rs3024505 homozygous wildtype carriers were at 27% reduced risk of CRC per 10 g fibre per day (95% CI: 0.60-0.88 whereas variant carriers had no risk reduction by fibre intake. Also, interaction between IL10 C-592A and intake of fibre was found (P-value for interaction = 0.02. Among those eating IL10 polymorphisms and dietary meat, cereal, or fish intake, or between IL10 rs3024505 and smoking or NSAID use were found. Conclusions In this northern Caucasian cohort we found interaction between IL10 and dietary fibre in CRC carcinogenesis. High intake of fibre seems to protect against CRC among individuals with IL10 related genetic susceptibility to CRC. This finding should be evaluated in other prospective and population-based cohorts with different ethnic groups.

Polymorphisms in NFKB1 and TLR4 and interaction with dietary and life style factors in relation to colorectal cancer in a Danish prospective case-cohort study.

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Kopp, Tine Iskov; Andersen, Vibeke; Tjonneland, Anne; Vogel, Ulla

2015-01-01

Maintenance of a balance between commensal bacteria and the mucosal immune system is crucial and intestinal dysbiosis may be a key event in the pathogenesis of colorectal cancer (CRC). The toll-like receptor 4 (TLR4) is an important pattern-recognition receptor that regulates inflammation and barrier function in the gut by a mechanism that involves activation of the nuclear factor-κB (NF-κB) transcription factor. Dietary and life style factors may impact these functions. We therefore used a Danish prospective case-cohort study of 1010 CRC cases and 1829 randomly selected participants from the Danish Diet, Cancer and Health cohort to investigate three polymorphisms in NFKB1 and TLR4 and their possible interactions with diet and life style factors in relation to risk of CRC. Homozygous carriage of the variant allele of the TLR4/rs5030728 polymorphism was associated with increased risk of CRC (incidence rate ratio (IRR) = 1.30; 95% confidence interval (CI): 1.05-1.60; P = 0.02 (gene-dose model); IRR = 1.24; 95%CI: 1.01-1.51; P = 0.04 (recessive model)). Del-carriers of the NFKB1/rs28362491 polymorphism had a 17% (95%CI: 1.03-1.34; P = 0.02) increased risk of CRC compared to homozygous carriers of the ins-allele. However, none of these risk estimates withstood adjustment for multiple comparisons. We found no strong gene-environment interactions between the examined polymorphism and diet and life style factors in relation to CRC risk.

Polymorphisms in NFKB1 and TLR4 and interaction with dietary and life style factors in relation to colorectal cancer in a Danish prospective case-cohort study.

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Tine Iskov Kopp

Full Text Available Maintenance of a balance between commensal bacteria and the mucosal immune system is crucial and intestinal dysbiosis may be a key event in the pathogenesis of colorectal cancer (CRC. The toll-like receptor 4 (TLR4 is an important pattern-recognition receptor that regulates inflammation and barrier function in the gut by a mechanism that involves activation of the nuclear factor-κB (NF-κB transcription factor. Dietary and life style factors may impact these functions. We therefore used a Danish prospective case-cohort study of 1010 CRC cases and 1829 randomly selected participants from the Danish Diet, Cancer and Health cohort to investigate three polymorphisms in NFKB1 and TLR4 and their possible interactions with diet and life style factors in relation to risk of CRC. Homozygous carriage of the variant allele of the TLR4/rs5030728 polymorphism was associated with increased risk of CRC (incidence rate ratio (IRR = 1.30; 95% confidence interval (CI: 1.05-1.60; P = 0.02 (gene-dose model; IRR = 1.24; 95%CI: 1.01-1.51; P = 0.04 (recessive model. Del-carriers of the NFKB1/rs28362491 polymorphism had a 17% (95%CI: 1.03-1.34; P = 0.02 increased risk of CRC compared to homozygous carriers of the ins-allele. However, none of these risk estimates withstood adjustment for multiple comparisons. We found no strong gene-environment interactions between the examined polymorphism and diet and life style factors in relation to CRC risk.

Serum apolipoprotein E concentration and polymorphism influence serum lipid levels in Chinese Shandong Han population.

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Han, ShuYi; Xu, YiHui; Gao, MeiHua; Wang, YunShan; Wang, Jun; Liu, YanYan; Wang, Min; Zhang, XiaoQian

2016-12-01

Apolipoprotein E (ApoE), which has been shown to influence serum lipid parameters, can bind to multiple types of lipids and plays an important role in the metabolism and homeostasis of lipids and lipoproteins. A previous study showed that ApoE concentration significantly affects serum lipid levels independently of ApoE polymorphism. The serum lipid levels were also closely correlated with dietary habits, and Shandong cuisine is famous for its high salt and oil contents, which widely differ among the different areas in China. Therefore, studying the effect of ApoE polymorphism on ApoE concentration and serum lipid levels in Shandong province is very important.A total of 815 subjects including 285 men and 530 women were randomly selected and studied from Jinan, Shandong province. In order to evaluate the association of ApoE polymorphism and serum level on lipid profiles, the ApoE genotypes, as well as levels of fasting serum ApoE and other lipid parameters, were detected in all subjects.The frequency of the ApoE E3 allele was highest (83.1%), while those of E2 and E4 were 9.4% and 7.5%, respectively, which are similar to those in other Asian populations. ApoE2 allele carriers showed significantly increased ApoE levels but lower levels of serum total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and Apolipoprotein B (ApoB).We found that ApoE level is influenced by ApoE polymorphism in a gene-dependent manner. The ApoE polymorphism showed different influences on serum lipid parameters with increasing age and body mass index (BMI) in our Shandong Han population.

Do methicillin resistant staphylococcus (MRSA) carrier patients influence MRSA infection more than MRSA-carrier medical officers and MRSA-carrier family?

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Dilogo, Ismail H; Arya, Abikara; Phedy; Loho, Tony

2013-07-01

to determine the rate of MRSA-carrier among patients, family members and health care providers, and the association between MRSA-carrier family members and health care providers on MRSA infection patient after orthopaedic surgery. this is a cross-sectional analytical study. Samples were taken consecutively during December 2010 to December 2011, consisting of postoperative patients infected with MRSA, attending family members, and the medical officers with history of contact with the patient. Swab culture were taken from nasal and axilla of all subjects. The incidence of MRSA infection, and MRSA-carrier on the patient, family members and medical officers were presented descriptively, while their association with MRSA infection was statistically tested using Fischer exact test. during the study period, there were 759 surgeries, with 4 (0.5%) patients were identified to have MRSA infection. Of these four cases, 48 subjects were enrolled. The rate of MRSA-carrier among patients, family and health care providers were 50%, 25% and 0% respectively. There were no significant association between MRSA and the rates of MRSA-carrier on the family member or health care providers. the incidence of MRSA infection, MRSA-carrier patient, MRSA-carrier health care providers, and family member carrier were 0.5%, 50%, 0%, and 25% respectively. No significant association found between MRSA-carrier on the family member or health care providers and MRSA infection patient. There were no MRSA infection found on the health care provider.

Association of MTHFR gene polymorphisms with breast cancer survival

International Nuclear Information System (INIS)

Martin, Damali N; Boersma, Brenda J; Howe, Tiffany M; Goodman, Julie E; Mechanic, Leah E; Chanock, Stephen J; Ambs, Stefan

2006-01-01

Two functional single nucleotide polymorphisms (SNPs) in the 5,10-methylenetetrahydrofolate reductase (MTHFR) gene, C677T and A1298C, lead to decreased enzyme activity and affect chemosensitivity of tumor cells. We investigated whether these MTHFR SNPs were associated with breast cancer survival in African-American and Caucasian women. African-American (n = 143) and Caucasian (n = 105) women, who had incident breast cancer with surgery, were recruited between 1993 and 2003 from the greater Baltimore area, Maryland, USA. Kaplan-Meier survival and multivariate Cox proportional hazards regression analyses were used to examine the relationship between MTHFR SNPs and disease-specific survival. We observed opposite effects of the MTHFR polymorphisms A1298C and C677T on breast cancer survival. Carriers of the variant allele at codon 1298 (A/C or C/C) had reduced survival when compared to homozygous carriers of the common A allele [Hazard ratio (HR) = 2.05; 95% confidence interval (CI), 1.05–4.00]. In contrast, breast cancer patients with the variant allele at codon 677 (C/T or T/T) had improved survival, albeit not statistically significant, when compared to individuals with the common C/C genotype (HR = 0.65; 95% CI, 0.31–1.35). The effects were stronger in patients with estrogen receptor-negative tumors (HR = 2.70; 95% CI, 1.17–6.23 for A/C or C/C versus A/A at codon 1298; HR = 0.36; 95% CI, 0.12–1.04 for C/T or T/T versus C/C at codon 677). Interactions between the two MTHFR genotypes and race/ethnicity on breast cancer survival were also observed (A1298C, p interaction = 0.088; C677T, p interaction = 0.026). We found that the MTHFR SNPs, C677T and A1298C, were associated with breast cancer survival. The variant alleles had opposite effects on disease outcome in the study population. Race/ethnicity modified the association between the two SNPs and breast cancer survival

Glycophorin C (Gerbich Antigen Blood Group) and Band 3 Polymorphisms in Two Malaria Holoendemic Regions of Papua New Guinea

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Patel, Sheral S.; King, Christopher L.; Mgone, Charles S.; Kazura, James W.; Zimmerman, Peter A.

2013-01-01

The geographic overlap between the prevalence of erythrocyte polymorphisms and malaria endemicity is thought to be an example of natural selection on human populations. In Papua New Guinea (PNG), the Gerbich-negative phenotype is caused by an exon 3 deletion in the glycophorin C gene (GYPCΔex3) while heterozygosity for a 27-base pair deletion in the SLC4A1 gene (anion exchanger 1 or erythrocyte membrane protein, band 3), SLC4A1Δ27, results in Southeast Asian ovalocytosis. Two geographically and ethnically distinct malaria endemic regions of PNG (the Wosera [East Sepik Province] and Liksul [Madang Province]) were studied to illustrate the distribution of two prominent deletion polymorphisms (GYPCΔex3 and SLC4A1Δ27) and to determine if the genetic load associated with SLC4A1Δ27 would constrain independent assortment of GYPCΔex3 heterozygous and homozygous genotypes. The frequency of the GYPCΔex3 allele was higher in the Wosera (0.463) than Liksul (0.176) (χ2; P < 0.0001). Conversely, the frequency of the SLC4A1Δ27 allele was higher in Liksul (0.0740) than the Wosera (0.0005) (χ2; P < 0.0001). No individuals were homozygous for SLC4A1Δ27. In 355 Liksul residents, independent assortment of these two deletion polymorphisms resulted in 14 SLC4A1Δ27 carriers heterozygous for GYPCΔex3 and one SLC4A1Δ27 carrier homozygous for GYPCΔex3 (Fisher’s exact test; P = 0.8040). While homozygosity for SLC4A1Δ27 appears to be nonviable, the GYPCΔex3 allele is not lethal when combined with SLC4A1Δ27. Neither mutation was associated with altered susceptibility to asymptomatic Plasmodium falciparum or P. vivax infection. While these erythrocyte polymorphisms apparently have no effect on blood-stage malaria infection, their contribution to susceptibility to clinical malaria morbidity requires further study. PMID:14695625

CYP2D6 gene polymorphisms in Brazilian patients with breast cancer treated with adjuvant tamoxifen and its association with disease recurrence

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De Ameida Melo, Mariella; De Vasconcelos-Valença, Rodrigo José; Neto, Fidelis Manes; Borges, Rafael Soares; Costa-Silva, Danylo Rafhael; Da Conceição Barros-Oliveira, Maria; Borges, Umbelina Soares; Alencar, Airlane Pereira; Silva, Vladimir Costa; Da Silva, Benedito Borges

2016-01-01

At present, there is controversy regarding the efficacy of tamoxifen in breast cancer patients who are carriers of cytochrome P450 2D6 (CYP2D6) gene polymorphisms, in terms of recurrence and overall survival. Thus, the aim of the present study was to investigate the association of the CYP2D6 *4, *10 and *17 gene polymorphisms with breast cancer recurrence in a Brazilian population. The cohort comprised 40 receptor-positive breast cancer patients without recurrence and 40 with distant recurrence. A 3-ml sample of peripheral blood was collected from each patient to determine the presence of the *4, *10 and *17 single nucleotide polymorphisms of the CYP2D6 gene by quantitative polymerase chain reaction analysis. There was no statistically significant difference between the two groups regarding the polymorphism frequency (P=0.246). The results revealed that intermediate metabolizers occurred in 5% of patients without recurrence and in 15% of those with distant recurrence. Poor metabolizers occurred in only 1 patient (2.5%) per group, and there was no significant difference between the groups (P=0.789). The present study concluded that the CYP2D6 gene polymorphism in women with hormone-sensitive breast cancer treated with tamoxifen was not associated with disease recurrence. PMID:27882219

PPARγ Pro12Ala and ACE ID polymorphisms are associated with BMI and fat distribution, but not metabolic syndrome

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Passaro Angela

2011-12-01

Full Text Available Abstract Background Metabolic Syndrome (MetS results from the combined effect of environmental and genetic factors. We investigated the possible association of peroxisome proliferator-activated receptor-γ2 (PPARγ2 Pro12Ala and Angiotensin Converting Enzyme (ACE I/D polymorphisms with MetS and interaction between these genetic variants. Methods Three hundred sixty four unrelated Caucasian subjects were enrolled. Waist circumference, blood pressure, and body mass index (BMI were recorded. Body composition was estimated by impedance analysis; MetS was diagnosed by the NCEP-ATPIII criteria. A fasting blood sample was obtained for glucose, insulin, lipid profile determination, and DNA isolation for genotyping. Results The prevalence of MetS did not differ across PPARγ2 or ACE polymorphisms. Carriers of PPARγ2 Ala allele had higher BMI and fat-mass but lower systolic blood pressure compared with Pro/Pro homozygotes. A significant PPARγ2 gene-gender interaction was observed in the modulation of BMI, fat mass, and blood pressure, with significant associations found in women only. A PPARγ2-ACE risk genotype combination for BMI and fat mass was found, with ACE DD/PPARγ2 Ala subjects having a higher BMI (p = 0.002 and Fat Mass (p = 0.002. Pro12Ala was independently associated with waist circumference independent of BMI and gender. Conclusions Carriers of PPARγ2 Ala allele had higher BMI and fat-mass but not a worse metabolic profile, possibly because of a more favorable adipose tissue distribution. A gene interaction exists between Pro12Ala and ACE I/D on BMI and fat mass. Further studies are needed to assess the contribution of Pro12Ala polymorphism in adiposity distribution.

The assessment of micronucleus frequency in lymphocytes in the cohort of coal-miners characterized by different polymorphisms of double strand break reparation genes

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Maxim Yur'yevich Sinitsky

2015-12-01

Full Text Available Background: Coal-miners are exposed to a lot of number of harmful factors (chemical agents, ionizing radiation, heavy metals, coal dust etc.. Material and methods: Venous blood samples extracted from 129 coal-miners. Assessment of cytogenetic damage was performed using the cytokinesis-block micronucleus assay (CBMN on peripheral blood lymphocytes. PCR and gel electrophoresis were used to determine polymorphisms in the genes Lig4 (rs1805388 and XRCC4 (rs6869366. Results: We found a significant increase in the frequency of binucleated lymphocytes with micronuclei (MN and protrusions in carriers of the Ile/ Ile genotype of the Lig4 gene Thr9Ile polymorphism in comparison to Thr/Thr and Thr/Ile genotypes. Conclusions: Thr9Ile polymorphism within Lig4 gene can be used as potential molecular genetic markers of increased individual susceptibility to the complex of harmful factors in coal-mining conditions.

Polymorphisms in the xenobiotic transporter Multidrug Resistance 1 (MDR1) and interaction with meat intake in relation to risk of colorectal cancer in a Danish prospective case-cohort study

DEFF Research Database (Denmark)

Andersen, Vibeke; Østergaard, Mette; Christensen, Jane

2009-01-01

(rs5275) polymorphisms in the 3'-untranslated region. The polymorphisms were assessed together with lifestyle factors in a nested case-cohort study of 359 cases and a random cohort sample of 765 participants from the Danish prospective Diet, Cancer and Health study. Results Carriers of the variant......Background The xenobiotic transporters, Multidrug Resistance 1 (MDR1/ABCB1) and Breast Cancer Resistance Protein (BCRP/ABCG2) may restrict intestinal absorption of various carcinogens, including heterocyclic amines (HCA) and polycyclic aromatic hydrocarbons (PAH). Cyclooxygenase-2 (COX-2) derived...... prostaglandins promote gastrointestinal carcinogenesis, affecting angiogenesis, apoptosis, and invasiveness. The aim of this study was to investigate if polymorphisms in these genes were associated with risk of colorectal cancer (CRC), and to investigate possible interactions with lifestyle factors...

Association of aplastic anemia and FoxP3 gene polymorphisms in Koreans.

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In, Ji Won; Lee, Nuri; Roh, Eun Youn; Shin, Sue; Park, Kyoung Un; Song, Eun Young

2017-04-01

Aplastic anemia (AA) is characterized by pancytopenia and bone marrow failure, and most acquired AA is an immune-mediated disorder. Regulatory T cells (T regs ) suppressing autoreactive T cells were decreased in AA patients. FoxP3 is a major regulator for the development and function of T regs . Polymorphism in FoxP3 was shown to be associated with various autoimmune diseases, however, has not yet been studied in AA. In this study, we examined the association between FoxP3 polymorphisms and AA in Korean patients. The study population consisted of 94 patients diagnosed by bone marrow examination in Seoul National University Hospital (SNUH) during 1997-2012 and 195 healthy controls. FoxP3 polymorphisms (rs5902434 del/ATT, rs3761548 C/A, rs3761549 C/T, rs2232365 A/G) were analyzed by PCR-sequencing method. We analyzed differences of genotype and allele frequencies between patients and controls. We also compared differences of genotype and allele frequencies between responder and non-responder in patients treated with immunosuppressive therapy (IST). For the statistical analysis, the chi-square test and Fisher's exact test were used and P < 0.05 was regarded as statistically significant. There was no significant difference in the genotype frequencies of FoxP3 polymorphisms between patients and controls. With regards to the allele frequencies, rs3761548 C allele was significantly higher in AA patients than in controls (87.4% vs. 79.7%, P = 0.047). In patients treated with IST, rs3761549 C allele was significantly higher in non-responder patients than in responders (89.6% vs. 66.7%, P = 0.036) and female rs3761549 C/C genotype carriers were associated with greater risk for non-response to IST (84.2% vs. 16.7%, P = 0.006). Polymorphisms in rs3761548 and rs3761549 of FoxP3 in our population were associated with disease susceptibility and response for IST, respectively. This study suggests an association between FoxP3 polymorphisms and AA in Korean patients

Association of APC I1307K and E1317Q polymorphisms with colorectal cancer among Egyptian subjects.

Science.gov (United States)

Abdel-Malak, Camelia; Darwish, Hossam; Elsaid, Afaf; El-Tarapely, Fatma; Elshazli, Rami

2016-01-01

Colorectal cancer is a multifactorial disease that involves both environmental and genetic factors. The gene encoding adenomatous polyposis coli (APC) has been reported to be associated with colorectal cancer (CRC) risk in several ethnic populations. The aim of this work is to assess the association of the APC I1307K and E1317Q polymorphisms with CRC risk among Egyptian subjects. This study included 120 unrelated CRC Egyptian patients who were compared to 100 healthy controls from the same locality. For all subjects, DNA was genotyped for APC I1307K and E1317Q polymorphisms using the PCR-ARMS technique. The frequency of APC I1307K carrier (TA+AA genotypes) was noted to be significantly higher among cases with CRC compared to controls (18.3 vs. 9.0 %, OR 2.58, 95 % CI 1.09-6.09, p = 0.03). Also the frequency of the APC I1307K A allele was significantly higher among cases compared to controls (10.4 vs. 4.5 %, OR 2.47; 95 % CI 1.12-5.42, p = 0.03). On the contrast, the frequencies of APC E1317Q GC genotype and C allele showed no significant difference among CRC patients compared to controls (3.3 vs. 2.0 %, OR 1.69; 95 % CI 0.30-9.42, p = 0.69 and 2.1 vs. 1.0 %, OR 2.11; 95 % CI 0.40-10.97, p = 0.46, respectively). Cases of the APC I1307K and E1317Q carriers (TA+AA and GC) showed no significant difference compared to those with I1307K and E1317Q non-carriers (TT and GG) regarding their clinical and laboratory markers. APC I1307K variant was associated with an increased risk of CRC among Egyptian subjects.

Hypoxia Inducible Factor-2 Alpha and Prolinhydroxylase 2 Polymorphisms in Patients with Acute Respiratory Distress Syndrome (ARDS

Directory of Open Access Journals (Sweden)

Annika Dötsch

2017-06-01

Full Text Available Hypoxia-inducible-factor-2α (HIF-2α and HIF-2 degrading prolyl-hydroxylases (PHD are key regulators of adaptive hypoxic responses i.e., in acute respiratory distress syndrome (ARDS. Specifically, functionally active genetic variants of HIF-2α (single nucleotide polymorphism (SNP [ch2:46441523(hg18] and PHD2 (C/T; SNP rs516651 and T/C; SNP rs480902 are associated with improved adaptation to hypoxia i.e., in high-altitude residents. However, little is known about these SNPs’ prevalence in Caucasians and impact on ARDS-outcome. Thus, we tested the hypotheses that in Caucasian ARDS patients SNPs in HIF-2α or PHD2 genes are (1 common, and (2 independent risk factors for 30-day mortality. After ethics-committee approval, 272 ARDS patients were prospectively included, genotyped for PHD2 (Taqman SNP Genotyping Assay and HIF-2α-polymorphism (restriction digest + agarose-gel visualization, and genotype dependent 30-day mortality was analyzed using Kaplan-Meier-plots and multivariate Cox-regression analyses. Frequencies were 99.62% for homozygous HIF-2α CC-carriers (CG: 0.38%; GG: 0%, 2.3% for homozygous PHD2 SNP rs516651 TT-carriers (CT: 18.9%; CC: 78.8%, and 3.7% for homozygous PHD2 SNP rs480902 TT-carriers (CT: 43.9%; CC: 52.4%. PHD2 rs516651 TT-genotype in ARDS was independently associated with a 3.34 times greater mortality risk (OR 3.34, CI 1.09–10.22; p = 0.034 within 30-days, whereas the other SNPs had no significant impact (p = ns. The homozygous HIF-2α GG-genotype was not present in our Caucasian ARDS cohort; however PHD2 SNPs exist in Caucasians, and PHD2 rs516651 TT-genotype was associated with an increased 30-day mortality suggesting a relevance for adaptive responses in ARDS.

14 CFR 399.82 - Passing off of carrier identity by affiliation between carriers.

Science.gov (United States)

2010-01-01

... forth in paragraph (c) of this section. In such cases the Board may determine in an adjudicatory... carrier shall not engage in joint public relations activities at points served by both carriers which tend... either carrier are performed in common with the other carrier or as part of a single system. In cases...

Cerebral 5-HT2A receptor and serotonin transporter binding in humans are not affected by the val66met BDNF polymorphism status or blood BDNF levels

DEFF Research Database (Denmark)

Klein, Anders Bue; Trajkovska, Viktorija; Erritzoe, David

2010-01-01

Recent studies have proposed an interrelation between the brain-derived neurotrophic factor (BDNF) val66met polymorphism and the serotonin system. In this study, we investigated whether the BDNF val66met polymorphism or blood BDNF levels are associated with cerebral 5-hydroxytryptamine 2A (5-HT(2A......)) receptor or serotonin transporter (SERT) binding in healthy subjects. No statistically significant differences in 5-HT(2A) receptor or SERT binding were found between the val/val and met carriers, nor were blood BDNF values associated with SERT binding or 5-HT(2A) receptor binding. In conclusion, val66met...... BDNF polymorphism status is not associated with changes in the serotonergic system. Moreover, BDNF levels in blood do not correlate with either 5-HT(2A) or SERT binding....

Mink S38G Gene Polymorphism and Atrial Fibrillation in the Chinese Population: A Meta-Analysis of 1871 Participants

Directory of Open Access Journals (Sweden)

Yan-yan Li

2014-01-01

Full Text Available Mink gene S38G polymorphism in the β-subunit of slow activating component of the delayed rectifier potassium channel current potassium channel has been associated with increased atrial fibrillation (AF risk. However, the individual studies results were still controversial. To investigate the association of Mink S38G gene polymorphisms with AF, a meta-analysis including 1871 subjects from six individual studies was conducted. Mink S38G gene polymorphism was significantly related to AF under allelic (OR: 1.380, 95% CI: 1.200–1.600, P<0.00001, recessive (OR: 1.193, 95% CI: 1.033–1.377, P=0.017, dominant (OR: 1.057, 95% CI: 1.025–1.089, P<0.00001, additive (OR: 1.105, 95% CI: 1.036–1.178, P=0.002, homozygous (OR: 1.128, 95% CI: 1.068–1.191, P<0.00001, and heterozygous genetic models (OR: 1.078, 95% CI: 1.014–1.146, P=0.016. A significant association between Mink S38G gene polymorphism and AF risk was found. G allele carriers may predispose to AF.

Impact of functional germline variants and a deletion polymorphism in APOBEC3A and APOBEC3B on breast cancer risk and survival in a Swedish study population.

Science.gov (United States)

Göhler, Stella; Da Silva Filho, Miguel Inacio; Johansson, Robert; Enquist-Olsson, Kerstin; Henriksson, Roger; Hemminki, Kari; Lenner, Per; Försti, Asta

2016-01-01

The C → T mutation signature caused by APOBEC family members contributes to the development of breast cancer (BC). Also overexpression of APOBEC3B and a ~29.5-kb deletion polymorphism between APOBEC3A and APOBEC3B have been associated with increased BC risk. We investigated in a population-based study, with 782 Swedish BC cases and 1559 controls, associations between potentially functional germline variants in APOBEC3A or APOBEC3B gene and BC risk and survival. Additionally, we identified deletion polymorphism carriers and explored possible associations with BC. No evidence of association between any germline variant, including the deletion polymorphism, and BC risk or survival was observed. Only APOBEC3A promoter polymorphism rs5757402 was associated with low stage (OR = 0.69, 95 % CI 0.50-0.96, dominant model). The reported association between the deletion polymorphism and BC risk was not confirmed in the Swedish population, nor did any genotyped germline variant show any association with BC risk or survival.

A haplotype of polymorphisms in ASE-1, RAI and ERCC1 and the effects of tobacco smoking and alcohol consumption on risk of colorectal cancer: a danish prospective case-cohort study

International Nuclear Information System (INIS)

Hansen, Rikke D; Sørensen, Mette; Tjønneland, Anne; Overvad, Kim; Wallin, Håkan; Raaschou-Nielsen, Ole; Vogel, Ulla

2008-01-01

Single nucleotide polymorphisms (SNPs) are the most frequent type of genetic variation in the human genome, and are of interest for the study of susceptibility to and protection from diseases. The haplotype at chromosome 19q13.2-3 encompassing the three SNPs ASE-1 G-21A, RAI IVS1 A4364G and ERCC1 Asn118Asn have been associated with risk of breast cancer and lung cancer. Haplotype carriers are defined as the homozygous carriers of RAI IVS1 A4364G A , ERCC1 Asn118Asn T and ASE-1 G-21A G . We aimed to evaluate whether the three polymorphisms and the haplotype are associated to risk of colorectal cancer, and investigated gene-environment associations between the polymorphisms and the haplotype and smoking status at enrolment, smoking duration, average smoking intensity and alcohol consumption, respectively, in relation to risk of colorectal cancer. Associations between the three individual polymorphisms, the haplotype and risk of colorectal cancer were examined, as well as gene-environment interaction, in a Danish case-cohort study including 405 cases and a comparison group of 810 persons. Incidence rate ratio (IRR) were estimated by the Cox proportional hazards model stratified according to gender, and two-sided 95% confidence intervals (CI) and p-values were calculated based on robust estimates of the variance-covariance matrix and Wald's test of the Cox regression parameter. No consistent associations between the three individual polymorphisms, the haplotype and risk of colorectal cancer were found. No statistically significant interactions between the genotypes and the lifestyle exposures smoking or alcohol consumption were observed. Our results suggest that the ASE-1 G-21A, RAI IVS1 A4364G and ERCC1 Asn118Asn polymorphisms and the previously identified haplotype are not associated with risk of colorectal cancer. We found no evidence of gene-environment interaction between the three polymorphisms and the haplotype and smoking intensity and alcohol consumption

Preparation and evaluation of famotidine polymorphs.

Science.gov (United States)

Nagaraju, Ravouru; Prathusha, Ande Penchala; Subhash Chandra Bose, Penjury; Kaza, Rajesh; Bharathi, Koganti

2010-06-01

The main objective of this study was to compare the behaviour of drug release among the famotidine polymorphs prepared by using various additives and solvents, by solvent evaporation method. The famotidine polyvinyl pyrrolidone polymorphs with different concentrations (0.5, 1 and 1.5%) were prepared by using solvent evaporation method. In these polymorphs of different concentrations 1% w/v polymorphs showed better release. Similarly, famotidine polymorphs of Tween 80 with different concentrations, polyethylene glycol 1% w/v and methanol was prepared. Famotidine polymorphs prepared the PVP (1% w/v) showed better drug release and solubility. DSC, FTIR, SEM and XRD studies were carried out. DSC studies revealed that PVP polymorphs were found to stable compared to other polymorphs. FTIR studies of the polymorphs prepared indicated that there was an interaction found in all polymorphs except PVP polymorphs indicating the absence of drug-additive interaction. SEM studies of PVP and methanol polymorphs revealed that they are tabular and prismatic and columnar respectively. These changes in morphology were due to variations in face dimensions and also properties of additives and solvent used in the preparation. XRD studies revealed that there is an increase in crystallinity in methanol polymorphs when compared to PVP polymorphs and pure drug. The mechanism of drug release was determined using zero order, first order and Hixon-Crowel equations. From the drug release kinetics these polymorphs followed first order and Hixon-Crowel release kinetics, exhibited fair linearity in their dissolution data. Further, in vivo studies were carried out for the evaluation of antiulcer activity. Based upon the drug release pattern and its kinetics only two of the prepared polymorphs of famotidine i.e. famotidine PVP polymorphs and famotidine methanol polymorphs were selected for animal studies. Antiulcer studies were carried out using pylorus ligation model and estimation of antioxidant

Effects of aripiprazole and the Taq1A polymorphism in the dopamine D2 receptor gene on the clinical response and plasma monoamine metabolites level during the acute phase of schizophrenia.

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Miura, Itaru; Takeuchi, Satoshi; Katsumi, Akihiko; Mori, Azuma; Kanno, Keiko; Yang, Qiaohui; Mashiko, Hirobumi; Numata, Yoshihiko; Niwa, Shin-Ichi

2012-02-01

The Taq1A polymorphism in the dopamine D2 receptor (DRD2) gene could be related to the response to antipsychotics. We examined the effects of the Taq1A polymorphism on the plasma monoamine metabolites during the treatment of schizophrenia with aripiprazole, a DRD2 partial agonist. Thirty Japanese patients with schizophrenia were treated with aripiprazole for 6 weeks. We measured plasma levels of homovanillic acid (pHVA) and 3-methoxy-4hydroxyphenylglycol (pMHPG) before and after treatment. The Taq1A polymorphism was genotyped with polymerase chain reaction. Aripiprazole improved the acute symptoms of schizophrenia and decreased pHVA in responders (P = 0.023) but not in nonresponders (P = 0.28). Although A1 allele carriers showed a tendency to respond to aripiprazole (61.5%) compared to A1 allele noncarriers (29.4%) (P = 0.078), there was not statistically significant difference in the response between the 2 genotype groups. There were significant effect for response (P = 0.013) and genotype × response interaction (P = 0.043) on the change of pHVA. The changes of pHVA differ between responders and nonresponders in A1 allele carriers but not in A1 allele noncarriers. There were no genotype or response effects or genotype × response interaction on the changes of the plasma levels of 3-methoxy-4hydroxyphenylglycol. Our preliminary results suggest that Taq1A polymorphism may be partly associated with changes in pHVA during acute schizophrenia.

Polymorphisms in the CNTF and CNTF receptor genes are associated with muscle strength in men and women.

Science.gov (United States)

De Mars, Gunther; Windelinckx, An; Beunen, Gaston; Delecluse, Christophe; Lefevre, Johan; Thomis, Martine A I

2007-05-01

Genotypic associations between polymorphisms in the ciliary neurotrophic factor (CNTF) and CNTF receptor (CNTFR) genes and muscular strength phenotypes in 154 middle-aged men (45-49 yr) and 138 women (38-44 yr) and 99 older men (60-78 yr) and 102 older women (60-80 yr) were tested to validate earlier association studies. Allelic interaction effects were hypothesized between alleles of CNTF and CNTFR. We performed analysis of covariance with age, height, and fat-free mass (FFM) as covariates. FFM was anthropometrically estimated by the equation of Durnin-Womersley. Isometric, concentric, and eccentric torques for the knee flexors (KF) and extensors (KE) were measured using Biodex dynamometry. In the older male group, T-allele carriers of the C-1703T polymorphism in CNTFR performed significantly better on all noncorrected KF torques, whereas only noncorrected KE isometric torque at 120 degrees and concentric torque at 240 degrees/s were higher than the C/C homozygotes (P men, with inconclusive results for a limited number of phenotypes in women. No significant CNTF/CNTFR allele interaction effects were found. Results indicate that CNTFR C-1703T and T1069A polymorphisms are significantly associated with muscle strength in humans.

Orthorhombic Ti2O3: A Polymorph-Dependent Narrow-Bandgap Ferromagnetic Oxide

KAUST Repository

Li, Yangyang

2017-12-16

Magnetic semiconductors are highly sought in spintronics, which allow not only the control of charge carriers like in traditional electronics, but also the control of spin states. However, almost all known magnetic semiconductors are featured with bandgaps larger than 1 eV, which limits their applications in long-wavelength regimes. In this work, the discovery of orthorhombic-structured Ti2O3 films is reported as a unique narrow-bandgap (≈0.1 eV) ferromagnetic oxide semiconductor. In contrast, the well-known corundum-structured Ti2O3 polymorph has an antiferromagnetic ground state. This comprehensive study on epitaxial Ti2O3 thin films reveals strong correlations between structure, electrical, and magnetic properties. The new orthorhombic Ti2O3 polymorph is found to be n-type with a very high electron concentration, while the bulk-type trigonal-structured Ti2O3 is p-type. More interestingly, in contrast to the antiferromagnetic ground state of trigonal bulk Ti2O3, unexpected ferromagnetism with a transition temperature well above room temperature is observed in the orthorhombic Ti2O3, which is confirmed by X-ray magnetic circular dichroism measurements. Using first-principles calculations, the ferromagnetism is attributed to a particular type of oxygen vacancies in the orthorhombic Ti2O3. The room-temperature ferromagnetism observed in orthorhombic-structured Ti2O3, demonstrates a new route toward controlling magnetism in epitaxial oxide films through selective stabilization of polymorph phases.

Orthorhombic Ti2O3: A Polymorph-Dependent Narrow-Bandgap Ferromagnetic Oxide

KAUST Repository

Li, Yangyang; Weng, Yakui; Yin, Xinmao; Yu, Xiaojiang; Sarath Kumar, S. R.; Wehbe, Nimer; Wu, Haijun; Alshareef, Husam N.; Pennycook, Stephen J.; Breese, Mark B. H.; Chen, Jingsheng; Dong, Shuai; Wu, Tao

2017-01-01

Magnetic semiconductors are highly sought in spintronics, which allow not only the control of charge carriers like in traditional electronics, but also the control of spin states. However, almost all known magnetic semiconductors are featured with bandgaps larger than 1 eV, which limits their applications in long-wavelength regimes. In this work, the discovery of orthorhombic-structured Ti2O3 films is reported as a unique narrow-bandgap (≈0.1 eV) ferromagnetic oxide semiconductor. In contrast, the well-known corundum-structured Ti2O3 polymorph has an antiferromagnetic ground state. This comprehensive study on epitaxial Ti2O3 thin films reveals strong correlations between structure, electrical, and magnetic properties. The new orthorhombic Ti2O3 polymorph is found to be n-type with a very high electron concentration, while the bulk-type trigonal-structured Ti2O3 is p-type. More interestingly, in contrast to the antiferromagnetic ground state of trigonal bulk Ti2O3, unexpected ferromagnetism with a transition temperature well above room temperature is observed in the orthorhombic Ti2O3, which is confirmed by X-ray magnetic circular dichroism measurements. Using first-principles calculations, the ferromagnetism is attributed to a particular type of oxygen vacancies in the orthorhombic Ti2O3. The room-temperature ferromagnetism observed in orthorhombic-structured Ti2O3, demonstrates a new route toward controlling magnetism in epitaxial oxide films through selective stabilization of polymorph phases.

Polymorphic Embedding of DSLs

DEFF Research Database (Denmark)

Hofer, Christian; Ostermann, Klaus; Rendel, Tillmann

2008-01-01

propose polymorphic embedding of DSLs, where many different interpretations of a DSL can be provided as reusable components, and show how polymorphic embedding can be realized in the programming language Scala. With polymorphic embedding, the static type-safety, modularity, composability and rapid...

Polymorphism rs3123554 in the cannabinoid receptor gene type 2 (CNR2) reveals effects on body weight and insulin resistance in obese subjects.

Science.gov (United States)

de Luis, Daniel Antonio; Izaola, Olatz; Primo, David; de la Fuente, Beatriz; Aller, Rocio

2017-10-01

Few studies assessing the relationship between single nucleotide polymorphisms in CNR2 and obesity or its related metabolic parameters are available. To investigate the influence of polymorphism rs3123554 in the CNR2 receptor gene on obesity anthropometric parameters, insulin resistance, and adipokines in subjects with obesity. The study population consisted of 1027 obese subjects, who were performed bioelectrical impedance analyses, blood pressure measurements, serial assessments of dietary intake during three days, and biochemical tests. Genotypes GG, GA, and AA were found in 339 (33.0%), 467 (45.5%), and 221 (21.5%) respectively. Body mass index, weight, fat mass, waist circumference, insulin, HOMA-IR, and triglyceride and leptin levels were higher in A-allele carriers as compared to non A-allele carriers. No differences were seen in these parameters between the GA and AA genotypes. There were no statistical differences in dietary intake. The main study finding was the association of the minor allele of the SNP rs3123554 in the CNR2 gene with body weight and triglyceride, HOMA-IR, insulin, and leptin levels. Copyright © 2017 SEEN y SED. Publicado por Elsevier España, S.L.U. All rights reserved.

The BDNF Val66Met polymorphism has opposite effects on memory circuits of multiple sclerosis patients and controls.

Directory of Open Access Journals (Sweden)

Francesco Fera

Full Text Available Episodic memory deficits are frequent symptoms in Multiple Sclerosis and have been associated with dysfunctions of the hippocampus, a key region for learning. However, it is unclear whether genetic factors that influence neural plasticity modulate episodic memory in MS. We thus studied how the Brain Derived Neurotrophic Factor Val(66Met genotype, a common polymorphism influencing the hippocampal function in healthy controls, impacted on brain networks underlying episodic memory in patients with Multiple Sclerosis. Functional magnetic resonance imaging was used to assess how the Brain Derived Neurotrophic Factor Val(66Met polymorphism modulated brain regional activity and functional connectivity in 26 cognitively unimpaired Multiple Sclerosis patients and 25 age- and education-matched healthy controls while performing an episodic memory task that included encoding and retrieving visual scenes. We found a highly significant group by genotype interaction in the left posterior hippocampus, bilateral parahippocampus, and left posterior cingulate cortex. In particular, Multiple Sclerosis patients homozygous for the Val(66 allele, relative to Met(66 carriers, showed greater brain responses during both encoding and retrieval while the opposite was true for healthy controls. Furthermore, a robust group by genotype by task interaction was detected for the functional connectivity between the left posterior hippocampus and the ipsilateral posterior cingulate cortex. Here, greater hippocampus-posterior cingulate cortex connectivity was observed in Multiple Sclerosis Met(66 carriers relative to Val(66 homozygous during retrieval (but not encoding while, again, the reverse was true for healthy controls. The Val(66Met polymorphism has opposite effects on hippocampal circuitry underlying episodic memory in Multiple Sclerosis patients and healthy controls. Enhancing the knowledge of how genetic factors influence cognitive functions may improve the clinical

Both Hemophilia Health Care Providers and Hemophilia A Carriers Report that Carriers have Excessive Bleeding

Science.gov (United States)

Paroskie, Allison; Oso, Olatunde; DeBaun, Michael R.; Sidonio, Robert F

2014-01-01

Introduction Hemophilia A, the result of reduced factor VIII (FVIII) activity, is an X-linked recessive bleeding disorder. Previous reports of Hemophilia A carriers suggest an increased bleeding tendency. Our objective was to determine the attitudes and understanding of the Hemophilia A carrier bleeding phenotype, and opinions regarding timing of carrier testing from the perspective of both medical providers and affected patients. Data from this survey was used as preliminary data for an ongoing prospective study. Material and Methods An electronic survey was distributed to physicians and nurses employed at Hemophilia Treatment Centers (HTC), and Hemophilia A carriers who were members of Hemophilia Federation of America. Questions focused on the clinical understanding of bleeding symptoms and management of Hemophilia A carriers, and the timing and intensity of carrier testing. Results Our survey indicates that 51% (36/51) of providers compared to 78% (36/46) of carriers believe that Hemophilia A carriers with normal FVIII activity have an increased bleeding tendency (pHemophilia A carriers report a high frequency of bleeding symptoms. Regarding carrier testing, 72% (50/69) of medical providers recommend testing after 14 years of age, conversely 65% (29/45) of Hemophilia A carriers prefer testing to be done prior to this age (pHemophilia A carriers self-report a higher frequency of bleeding than previously acknowledged, and have a preference for earlier testing to confirm carrier status. PMID:24309601

Association of ITPA polymorphisms rs6051702/rs1127354 instead of rs7270101/rs1127354 as predictor of ribavirin-associated anemia in chronic hepatitis C treated patients.

Science.gov (United States)

D'Avolio, Antonio; De Nicolò, Amedeo; Cusato, Jessica; Ciancio, Alessia; Boglione, Lucio; Strona, Silvia; Cariti, Giuseppe; Troshina, Giulia; Caviglia, Gian Paolo; Smedile, Antonina; Rizzetto, Mario; Di Perri, Giovanni

2013-10-01

Functional variants rs7270101 and rs1127354 of inosine triphosphatase (ITPA) were recently found to protect against ribavirin (RBV)-induced hemolytic anemia. However, no definitive data are yet available on the role of no functional rs6051702 polymorphism. Since a simultaneous evaluation of the three ITPA SNPs for hemolytic anemia has not yet been investigated, we aimed to understand the contribution of each SNPs and its potential clinical use to predict anemia in HCV treated patients. A retrospective analysis included 379 HCV treated patients. The ITPA variants rs6051702, rs7270101 and rs1127354 were genotyped and tested for association with achieving anemia at week 4. We also investigated, using multivariate logistic regression, the impact of each single and paired associated polymorphism on anemia onset. All SNPs were associated with Hb decrease. The carrier of at least one variant allele in the functional ITPA SNPs was associated with a lower decrement of Hb, as compared to patients without a variant allele. In multivariate logistic regression analyses the carrier of a variant allele in the rs6051702/rs1127354 association (OR=0.11, p=1.75×10(-5)) and Hb at baseline (OR=1.51, p=1.21×10(-4)) were independently associated with protection against clinically significant anemia at week 4. All ITPA polymorphisms considered were shown to be significantly associated with anemia onset. A multivariate regression model based on ITPA genetic polymorphisms was developed for predicting the risk of anemia. Considering the characterization of pre-therapy anemia predictors, rs6051702 SNP in association to rs1127354 is more informative in order to avoid this relevant adverse event. Copyright © 2013 Elsevier B.V. All rights reserved.

A non-synonymous polymorphism in IRS1 modifies risk of developing breast and ovarian cancers in BRCA1 and ovarian cancer in BRCA2 mutation carriers

Science.gov (United States)

Ding, Yuan C.; McGuffog, Lesley; Healey, Sue; Friedman, Eitan; Laitman, Yael; Shani-Shimon–Paluch; Kaufman, Bella; Liljegren, Annelie; Lindblom, Annika; Olsson, Håkan; Kristoffersson, Ulf; Stenmark-Askmalm, Marie; Melin, Beatrice; Domchek, Susan M.; Nathanson, Katherine L.; Rebbeck, Timothy R.; Jakubowska, Anna; Lubinski, Jan; Jaworska, Katarzyna; Durda, Katarzyna; Gronwald, Jacek; Huzarski, Tomasz; Cybulski, Cezary; Byrski, Tomasz; Osorio, Ana; Cajal, Teresa Ramóny; Stavropoulou, Alexandra V; Benítez, Javier; Hamann, Ute; Rookus, Matti; Aalfs, Cora M.; de Lange, Judith L.; Meijers-Heijboer, Hanne E.J.; Oosterwijk, Jan C.; van Asperen, Christi J.; García, Encarna B. Gómez; Hoogerbrugge, Nicoline; Jager, Agnes; van der Luijt, Rob B.; Easton, Douglas F.; Peock, Susan; Frost, Debra; Ellis, Steve D.; Platte, Radka; Fineberg, Elena; Evans, D. Gareth; Lalloo, Fiona; Izatt, Louise; Eeles, Ros; Adlard, Julian; Davidson, Rosemarie; Eccles, Diana; Cole, Trevor; Cook, Jackie; Brewer, Carole; Tischkowitz, Marc; Godwin, Andrew K.; Pathak, Harsh; Stoppa-Lyonnet, Dominique; Sinilnikova, Olga M.; Mazoyer, Sylvie; Barjhoux, Laure; Léoné, Mélanie; Gauthier-Villars, Marion; Caux-Moncoutier, Virginie; de Pauw, Antoine; Hardouin, Agnès; Berthet, Pascaline; Dreyfus, Hélène; Ferrer, Sandra Fert; Collonge-Rame, Marie-Agnès; Sokolowska, Johanna; Buys, Saundra; Daly, Mary; Miron, Alex; Terry, Mary Beth; Chung, Wendy; John, Esther M; Southey, Melissa; Goldgar, David; Singer, Christian F; Maria, Muy-Kheng Tea; Gschwantler-Kaulich, Daphne; Fink-Retter, Anneliese; Hansen, Thomas v. O.; Ejlertsen, Bent; Johannsson, Oskar Th.; Offit, Kenneth; Sarrel, Kara; Gaudet, Mia M.; Vijai, Joseph; Robson, Mark; Piedmonte, Marion R; Andrews, Lesley; Cohn, David; DeMars, Leslie R.; DiSilvestro, Paul; Rodriguez, Gustavo; Toland, Amanda Ewart; Montagna, Marco; Agata, Simona; Imyanitov, Evgeny; Isaacs, Claudine; Janavicius, Ramunas; Lazaro, Conxi; Blanco, Ignacio; Ramus, Susan J; Sucheston, Lara; Karlan, Beth Y.; Gross, Jenny; Ganz, Patricia A.; Beattie, Mary S.; Schmutzler, Rita K.; Wappenschmidt, Barbara; Meindl, Alfons; Arnold, Norbert; Niederacher, Dieter; Preisler-Adams, Sabine; Gadzicki, Dorotehea; Varon-Mateeva, Raymonda; Deissler, Helmut; Gehrig, Andrea; Sutter, Christian; Kast, Karin; Nevanlinna, Heli; Aittomäki, Kristiina; Simard, Jacques; Spurdle, Amanda B.; Beesley, Jonathan; Chen, Xiaoqing; Tomlinson, Gail E.; Weitzel, Jeffrey; Garber, Judy E.; Olopade, Olufunmilayo I.; Rubinstein, Wendy S.; Tung, Nadine; Blum, Joanne L.; Narod, Steven A.; Brummel, Sean; Gillen, Daniel L.; Lindor, Noralane; Fredericksen, Zachary; Pankratz, Vernon S.; Couch, Fergus J.; Radice, Paolo; Peterlongo, Paolo; Greene, Mark H.; Loud, Jennifer T.; Mai, Phuong L.; Andrulis, Irene L.; Glendon, Gord; Ozcelik, Hilmi; Gerdes, Anne-Marie; Thomassen, Mads; Jensen, Uffe Birk; Skytte, Anne-Bine; Caligo, Maria A.; Lee, Andrew; Chenevix-Trench, Georgia; Antoniou, Antonis C; Neuhausen, Susan L.

2012-01-01

Background We previously reported significant associations between genetic variants in insulin receptor substrate 1 (IRS1) and breast cancer risk in women carrying BRCA1 mutations. The objectives of this study were to investigate whether the IRS1 variants modified ovarian cancer risk and were associated with breast cancer risk in a larger cohort of BRCA1 and BRCA2 mutation carriers. Methods IRS1 rs1801123, rs1330645, and rs1801278 were genotyped in samples from 36 centers in the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA). Data were analyzed by a retrospective cohort approach modeling the associations with breast and ovarian cancer risks simultaneously. Analyses were stratified by BRCA1 and BRCA2 status and mutation class in BRCA1 carriers. Results Rs1801278 (Gly972Arg) was associated with ovarian cancer risk for both BRCA1 [Hazard ratio (HR) = 1.43; 95% CI: 1.06–1.92; p = 0.019] and BRCA2 mutation carriers (HR=2.21; 95% CI: 1.39–3.52, p=0.0008). For BRCA1 mutation carriers, the breast cancer risk was higher in carriers with class 2 mutations than class 1 (mutations (class 2 HR=1.86, 95% CI: 1.28–2.70; class 1 HR=0.86, 95%CI:0.69–1.09; p-for difference=0.0006). Rs13306465 was associated with ovarian cancer risk in BRCA1 class 2 mutation carriers (HR = 2.42; p = 0.03). Conclusion The IRS1 Gly972Arg SNP, which affects insulin-like growth factor and insulin signaling, modifies ovarian cancer risk in BRCA1 and BRCA2 mutation carriers and breast cancer risk in BRCA1 class 2 mutation carriers. Impact These findings may prove useful for risk prediction for breast and ovarian cancers in BRCA1 and BRCA2 mutation carriers. PMID:22729394

Effects of MCF2L2, ADIPOQ and SOX2 genetic polymorphisms on the development of nephropathy in type 1 Diabetes Mellitus

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Gu Harvest F

2010-07-01

Full Text Available Abstract Background MCF2L2, ADIPOQ and SOX2 genes are located in chromosome 3q26-27, which is linked to diabetic nephropathy (DN. ADIPOQ and SOX2 genetic polymorphisms are found to be associated with DN. In the present study, we first investigated the association between MCF2L2 and DN, and then evaluated effects of these three genes on the development of DN. Methods A total of 1177 type 1 diabetes patients with and without DN from the GoKinD study were genotyped with TaqMan allelic discrimination. All subjects were of European descent. Results Leu359Ile T/G variant in the MCF2L2 gene was found to be associated with DN in female subjects (P = 0.017, OR = 0.701, 95%CI 0.524-0.938 but not in males. The GG genotype carriers among female patients with DN had tendency decreased creatinine and cystatin levels compared to the carriers with either TT or TG genotypes. This polymorphism MCF2L2-rs7639705 together with SNPs of ADIPOQ-rs266729 and SOX2-rs11915160 had combined effects on decreased risk of DN in females (P = 0.001. Conclusion The present study provides evidence that MCF2L2, ADIPOQ and SOX2 genetic polymorphisms have effects on the resistance of DN in female T1D patients, and suggests that the linkage with DN in chromosome 3q may be explained by the cumulated genetic effects.

CYP2E1 Rsa Ι/Pst Ι polymorphism and lung cancer susceptibility: a meta-analysis involving 10,947 subjects.

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Shen, Ze-Tian; Wu, Xin-Hu; Li, Bing; Shen, Jun-shu; Wang, Zhen; Li, Jing; Zhu, Xi-Xu

2015-09-01

Many studies have examined the association between the CYP2E1 Rsa Ι/Pst Ι (rs3813867) polymorphism gene polymorphisms and lung cancer risk in various populations, but their results have been inconsistent. The PubMed and CNKI database was searched for case-control studies published up to October 2013. Data were extracted and pooled odds ratios (OR) with 95% confidence intervals (CI) were calculated. In this meta-analysis, we assessed 23 published studies involving comprising 4727 lung cancer cases and 6220 controls of the association between CYP2E1 Rsa Ι/Pst Ι polymorphism and lung cancer risk. For the homozygote c2/c2 and c2 allele carriers (c1/c2 + c2/c2), the pooled ORs for all studies were 0.73(95% CI = 0.62-0.84; P = 0.005 for heterogeneity) and 0.84 (95% CI = 0.77-0.92; P = 0.001 for heterogeneity) when compared with the homozygous wild-type genotype (c1/c1). In the stratified analysis by ethnicity, the same significantly risks were found among Asians and mixed population for both the c2 allele carriers and homozygote c2/c2. However, no significant associations were found in Caucasian population all genetic models. This updated meta-analysis suggests that CYP2E1 Rsa Ι/Pst Ι c2 allele is a decreased risk factor for the developing lung cancer among Asians and mixed population. © 2015 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

Association of the CC genotype of the regulatory BCL2 promoter polymorphism (-938C>A) with better 2-year survival in patients with glioblastoma multiforme.

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El Hindy, Nicolai; Bachmann, Hagen S; Lambertz, Nicole; Adamzik, Michael; Nückel, Holger; Worm, Karl; Zhu, Yuan; Sure, Ulrich; Siffert, Winfried; Sandalcioglu, I Erol

2011-06-01

Bcl-2 plays a key role in the downregulation of apoptosis and proliferation and leads to increased chemoresistance in glioblastoma multiforme (GBM). The authors investigated the role of a common regulatory single-nucleotide polymorphism (-938C>A), which is located in the inhibitory P2 promoter of BCL2. Data from 160 patients suffering from GBM were retrospectively evaluated. Study inclusion criteria consisted of available DNA and, in patients still alive, a follow-up of at least 24 months. Results were analyzed with respect to the basic clinical data, type of surgical intervention (gross-total resection [GTR] versus stereotactic biopsy [SB]), adjuvant therapy, MGMT promoter methylation, and survival at the 2-year follow-up. At the 2-year follow-up, 127 (79.4%) of the 160 patients had died. Kaplan-Meier curves revealed a significantly higher rate of survival for homo- and heterozygous C-allele carriers (p = 0.031). In the GTR group, the survival rate was 47.1% for homozygous C-allele carriers, 32.0% for heterozygous C-allele carriers, and only 21.4% for homozygous A-allele carriers (p = 0.024). The SB group showed no genotype-dependent differences. Multivariable Cox regression revealed that the BCL2 (-938AA) genotype was an independent negative prognostic factor for 2-year survival in the GTR group according to the BCL2 (-938CC) genotype reference group (hazard ratio 2.50, 95% CI 1.14-5.48, p = 0.022). These results suggested that the (-938C>A) polymorphism is a survival prognosticator as well as a marker for a high-risk group among patients with GBM who underwent GTR.

A Genetic Polymorphism in RBP4 Is Associated with Coronary Artery Disease

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Ke Wan

2014-12-01

Full Text Available Insulin resistance and obesity is influenced by the retinol binding protein 4 (RBP4 adipokine. This study aims to determine if genetic polymorphisms in RBP4 are associated with the risk of coronary artery disease (CAD in Chinese patients. RBP4 polymorphisms were analyzed by high resolution melting (HRM analysis in a case-control study of 392 unrelated CAD patients and 368 controls from China. The Gensini score was used to determine the severity of CAD. The genotypic and allelic frequencies of RBP4 single-nucleotide polymorphisms were evaluated for associations with CAD and severity of disease. The A allele frequency was significantly higher in CAD case groups compared to control groups (16.7% vs. 8.8% at the RBP4 rs7094671 locus. Compared to the G allele, this allele was associated with a higher risk of CAD (OR = 2.07 (1.50–2.84. Polymorphisms at rs7094671 were found to associate with CAD using either a dominant or recessive model (OR, 95% CI: 1.97, 1.38–2.81; 3.81, 1.53–9.51, respectively. Adjusting for sex, history of smoking, serum TC, TG, LDL-c, and HDL-c, the risk of CAD for carriers remained significantly higher in both dominant and recessive models (OR, 95% CI: 1.68, 1.12–2.51; 2.74, 1.00–7.52, respectively. However, this SNP was not significantly associated with severity of CAD using angiographic scores in multivariable linear regression models (p = 0.373. The RBP4 rs7094671 SNP is associated with CAD; however, our results do not indicate that this locus is associated with clinical severity of CAD or the extent of coronary lesions.

Psychiatric and cognitive symptoms in Huntington's disease are modified by polymorphisms in catecholamine regulating enzyme genes

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Vinther-Jensen, T; Nielsen, Troels Tolstrup; Budtz-Jørgensen, E

2016-01-01

Huntington's disease (HD) is an autosomal dominantly inherited neurodegenerative disorder characterized by motor, psychiatric, and cognitive manifestations. HD is caused by a CAG repeat expansion in the Huntingtin (HTT) gene but the exact pathogenesis remains unknown. Dopamine imbalance has......-described cohort of Danish HD gene-expansion carriers. We show that cognitive impairment and psychiatric symptoms in HD are modified by polymorphisms in the monoamine oxidase A (MAOA) and catechol-O-methyltransferase (COMT) genes and by the 4p16.3 B haplotype. These results support the theory of dopamine imbalance...

Impacts of CA9 gene polymorphisms on urothelial cell carcinoma susceptibility and clinicopathologic characteristics in Taiwan.

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Shian-Shiang Wang

Full Text Available Carbonic anhydrase 9 (CA9 is reportedly overexpressed in several types of carcinomas and is generally considered a marker of malignancy. The current study explored the effect of CA9 gene polymorphisms on the susceptibility of developing urothelial cell carcinoma (UCC and the clinicopathological status.A total of 442 participants, including 221 healthy people and 221 patients with UCC, were recruited for this study. Four single-nucleotide polymorphisms (SNPs of the CA9 gene were assessed by a real-time PCR with the TaqMan assay. After adjusting for other co-variants, the individuals carrying at least one A allele at CA9 rs1048638 had a 2.303-fold risk of developing UCC than did wild-type (CC carriers. Furthermore, UCC patients who carried at least one A allele at rs1048638 had a higher invasive stage risk (p< 0.05 than did patients carrying the wild-type allele. Moreover, among the UCC patients with smoker, people with at least one A allele of CA9 polymorphisms (rs1048638 had a 4.75-fold (95% CI = 1.204-18.746 increased risk of invasive cancer.The rs1048638 polymorphic genotypes of CA9 might contribute to the prediction of susceptibility to and pathological development of UCC. This is the first study to provide insight into risk factors associated with CA9 variants in carcinogenesis of UCC in Taiwan.

Genetic polymorphisms potentially associated with response to metformin in postmenopausal diabetics suffering and not suffering with cancer.

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Berstein, Lev M; Iyevleva, Aglaya G; Vasilyev, Dmitry; Poroshina, Tatyana E; Imyanitov, Evgeny N

2013-12-01

Metformin is a well-known antidiabetic medication, which, besides diabetes, may be involved into modulation of other age-related pathologies, including cancer. The study concerns 12 gene polymorphisms divided into 2 groups consisting of 6 genes each. The first group was composed from so-called "standard" (S) polymorphisms, for which the connection with metabolic response to metformin is already established. The second group included polymorphisms of genes encoding proteins possibly connected with diabetes mellitus type 2 (DM2), impaired glucose tolerance or cancer and entitled here as "associated" (A). A total of 156 postmenopausal women (average age 60.7 ± 0.7) were included, 37 of them healthy, 64 with type DM2 and concurrent treatment-naïve cancer (mostly breast, endometrial or colorectal cancer), 32 with DM2 without cancer, and 23 with treatment-naïve cancer and normal glucose tolerance. The leading metformin response S-marker in combined group of DM2 patients was the CC variant of OCT1-R61C polymorphism of organic cation transporter protein 1 gene. In cancer patients without DM2, this position belonged to AC and AA genotypes of OCT1_rs622342 polymorphism. Among the A-polymorphisms, GA variant of sex hormone-binding globulin gene SHBG_D356N was less frequently observed in DM2 patients with or without cancer. Besides, in diabetics, the same polymorphic variant of SHBG as well as GC genotype of oxidized lipoprotein receptor OLR1_G501C and GG genotype of locus rs11065987 near BRAP gene were carried rather often in combination with "metformin-positive" variant of OCT1_R61C. In addition, carriers of OCT1_R61C and OCT1_rs622342 polymorphisms with potentially positive reaction to metformin had higher insulin resistance score (HOMA-IR) values. Received data lead to the conclusion that postmenopausal diabetics, both with and without cancer, differ in genetic stigmata of potential response to metformin less than they differ from cancer patients without DM2. As genetic

GLUTATHIONE PEROXIDASE-1 PRO200LEU POLYMORPHISM (RS1050450) IS ASSOCIATED WITH MORBID OBESITY INDEPENDENTLY OF THE PRESENCE OF PREDIABETES OR DIABETES IN WOMEN FROM CENTRAL MEXICO.

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Hernández Guerrero, César; Hernández Chávez, Paulina; Martínez Castro, Noemí; Parra Carriedo, Alicia; García Del Rio, Sandra; Pérez Lizaur, Ana

2015-10-01

obesity affects more than a third of Mexican population. Oxidative stress participates actively in the etiology of this phenomenon. Glutathione peroxidase-1 (GPX-1) plays a protective role against oxidative stress. The SNP Pro200Leu (rs10504050) has been reported to affect the activity of the enzyme. to determine the frequency of rs10504050 polymorphism in women with obesity and normal weight control, asses the concentration of peripheral TBARS and evaluate the consumption of pro and antioxidants. 104 women with obesity and 70 healthy controls (CG) were included in the study. Anthropometric, biochemical, clinical and dietary features were evaluated. GPx-1 rs10504050 was determined by PCR/RFLP method. TBARS was assayed spectrophotometrically in plasma. The subjects were stratified and compared by obesity grades and by subgroups of prediabetes and diabetes condition. Statistical analysis included ANOVA of Kruskal Wallis, Xi squared and Pearson correlation. for rs10504050 polymorphism there were differences (Xi2 = 6; p = 0.01) between frequency (0.61) of obese carriers (Pro/Leu plus Leu/Leu) and CG carriers (0.42), and between (Xi2 = 8; p = 0.004) morbid (IMC > 40) obesity (0.74) and CG carriers. The obese group (OB) showed a prevalence of 66% of prediabetes plus diabetes. There were no differences in frequencies of rs10504050 in OB with pre or diabetes versus CG, or versus obese participants without diabetes. TBARS concentration was greater in all the degrees of OB versus CG. GPx-1 Pro200Leu polymorphism was associated with obesity especially with morbid obesity, but not with obese participants with prediabetes or diabetes. Oxidative stress is present in all grades of obesity significantly. Copyright AULA MEDICA EDICIONES 2014. Published by AULA MEDICA. All rights reserved.

THE INFLUENCE OF POLYMORPHISM IN THE INFLAMMATORY GENES IL-1, ß IL-6, IL-10, PPAR?2 AND COX-2 IN PATIENTS WITH MULTIPLE MYELOMA UNDERGOING AUTOLOGOUS BONE MARROW TRANSPLANTATION

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Vangsted, Annette; Klausen, Tobias W.; Gimsing, Peter

2007-01-01

in genes involved in the inflammatory response in 348 patients undergoing high dose treatment followed by autologous tem cell transplantation. We found that the polymorphism in IL-1ß T-31C significantly influence overall survival (p=0.02). Homozygous carriers of the variant C-allele had a significantly...

Single Nucleotide Polymorphisms in the FADS Gene Cluster but not the ELOVL2 Gene are Associated with Serum Polyunsaturated Fatty Acid Composition and Development of Allergy (in a Swedish Birth Cohort

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Malin Barman

2015-12-01

Full Text Available Exposure to polyunsaturated fatty acids (PUFA influences immune function and may affect the risk of allergy development. Long chain PUFAs are produced from dietary precursors catalyzed by desaturases and elongases encoded by FADS and ELOVL genes. In 211 subjects, we investigated whether polymorphisms in the FADS gene cluster and the ELOVL2 gene were associated with allergy or PUFA composition in serum phospholipids in a Swedish birth-cohort sampled at birth and at 13 years of age; allergy was diagnosed at 13 years of age. Minor allele carriers of rs102275 and rs174448 (FADS gene cluster had decreased proportions of 20:4 n-6 in cord and adolescent serum and increased proportions of 20:3 n-6 in cord serum as well as a nominally reduced risk of developing atopic eczema, but not respiratory allergy, at 13 years of age. Minor allele carriers of rs17606561 in the ELOVL2 gene had nominally decreased proportions of 20:4 n-6 in cord serum but ELOVL polymorphisms (rs2236212 and rs17606561 were not associated with allergy development. Thus, reduced capacity to desaturase n-6 PUFAs due to FADS polymorphisms was nominally associated with reduced risk for eczema development, which could indicate a pathogenic role for long-chain PUFAs in allergy development.

An IGF-I promoter polymorphism modifies the relationships between birth weight and risk factors for cardiovascular disease and diabetes at age 36

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Stehouwer Coen DA

2005-06-01

Full Text Available Abstract Objective To investigate whether IGF-I promoter polymorphism was associated with birth weight and risk factors for cardiovascular disease (CVD and type 2 diabetes (T2DM, and whether the birth weight – risk factor relationship was the same for each genotype. Design and participants 264 subjects (mean age 36 years had data available on birth weight, IGF-I promoter polymorphism genotype, CVD and T2DM risk factors. Student's t-test and regression analyses were applied to analyse differences in birth weight and differences in the birth weight – risk factors relationship between the genotypes. Results Male variant carriers (VCs of the IGF-I promoter polymorphism had a 0.2 kg lower birth weight than men with the wild type allele (p = 0.009. Of the risk factors for CVD and T2DM, solely LDL concentration was associated with the genotype for the polymorphism. Most birth weight – risk factor relationships were stronger in the VC subjects; among others the birth weight – systolic blood pressure relationship: 1 kg lower birth weight was related to an 8.0 mmHg higher systolic blood pressure Conclusion The polymorphism in the promoter region of the IGF-I gene is related to birth weight in men only, and to LDL concentration only. Furthermore, the genotype for this polymorphism modified the relationships between birth weight and the risk factors, especially for systolic and diastolic blood pressure.

The moderating role of an oxytocin receptor gene polymorphism in the relation between unsupportive social interactions and coping profiles: Implications for depression

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Opal Arilla Mcinnis

2015-08-01

Full Text Available Oxytocin is a hormone that is thought to influence prosocial behaviors and may be important in modulating responses to both positive and negative social interactions. Indeed, a single nucleotide polymorphism (SNP of the oxytocin receptor gene (OXTR has been associated with decreased trust, empathy, optimism and social support seeking, which are important components of coping with stressors. In the current study, conducted among undergraduate students (N=225, it was shown that parental and peer social support was related to fewer depressive symptoms through elevated problem-focused coping and lower emotion-focused coping, and these effects were independent of the OXTR polymorphism. Unsupportive social interactions from parents were associated with more severe depressive symptoms through the greater use of emotion-focused coping, and this relation was moderated by the OXTR genotype. Specifically, individuals who carried the polymorphism on one or both of their alleles demonstrated increased emotion-focused coping following unsupportive responses compared to those without the polymorphism. Likewise, lower problem-focused coping mediated the relation between parental and peer unsupportive responses to depressive symptoms, but this mediated relation was only evident among carriers of the polymorphism. These findings suggest that carrying this OXTR polymorphism might favor disadvantageous coping styles in the face of negative social interactions, which in turn are linked to poor mood. Regardless of genotype, parental and peer social support are fundamental in determining stress-related coping and well-being.

APOBEC3A is an oral cancer prognostic biomarker in Taiwanese carriers of an APOBEC deletion polymorphism.

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Chen, Ting-Wen; Lee, Chi-Ching; Liu, Hsuan; Wu, Chi-Sheng; Pickering, Curtis R; Huang, Po-Jung; Wang, Jing; Chang, Ian Yi-Feng; Yeh, Yuan-Ming; Chen, Chih-De; Li, Hsin-Pai; Luo, Ji-Dung; Tan, Bertrand Chin-Ming; Chan, Timothy En Haw; Hsueh, Chuen; Chu, Lichieh Julie; Chen, Yi-Ting; Zhang, Bing; Yang, Chia-Yu; Wu, Chih-Ching; Hsu, Chia-Wei; See, Lai-Chu; Tang, Petrus; Yu, Jau-Song; Liao, Wei-Chao; Chiang, Wei-Fan; Rodriguez, Henry; Myers, Jeffrey N; Chang, Kai-Ping; Chang, Yu-Sun

2017-09-06

Oral squamous cell carcinoma is a prominent cancer worldwide, particularly in Taiwan. By integrating omics analyses in 50 matched samples, we uncover in Taiwanese patients a predominant mutation signature associated with cytidine deaminase APOBEC, which correlates with the upregulation of APOBEC3A expression in the APOBEC3 gene cluster at 22q13. APOBEC3A expression is significantly higher in tumors carrying APOBEC3B-deletion allele(s). High-level APOBEC3A expression is associated with better overall survival, especially among patients carrying APOBEC3B-deletion alleles, as examined in a second cohort (n = 188; p = 0.004). The frequency of APOBEC3B-deletion alleles is ~50% in 143 genotyped oral squamous cell carcinoma -Taiwan samples (27A3B -/- :89A3B +/- :27A3B +/+ ), compared to the 5.8% found in 314 OSCC-TCGA samples. We thus report a frequent APOBEC mutational profile, which relates to a APOBEC3B-deletion germline polymorphism in Taiwanese oral squamous cell carcinoma that impacts expression of APOBEC3A, and is shown to be of clinical prognostic relevance. Our finding might be recapitulated by genomic studies in other cancer types.Oral squamous cell carcinoma is a prevalent malignancy in Taiwan. Here, the authors show that OSCC in Taiwanese show a frequent deletion polymorphism in the cytidine deaminases gene cluster APOBEC3 resulting in increased expression of A3A, which is shown to be of clinical prognostic relevance.

Relationship between glycemic control and OPG gene polymorphisms with lower bone mineral density in patients with type 1 Diabetes mellitus

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Melina Bezerra Loureiro

2018-04-01

Full Text Available ABSTRACT The aim of the present study was to investigate the bone mineral density (BMD of patients with type 1 Diabetes mellitus (T1DM. We also assessed the association between osteoprotegerin (OPG genetic polymorphisms and BMD. Genotyping was performed for 1181G>C and 163A>G OPG polymorphisms by allelic discrimination in 119 patients with T1DM and 161 normoglycemic (NG individuals, aged 6 to 20 years old. Glycemic control, serum parameters of bone metabolism and BMD were evaluated. T1DM patients showed low BMD, poor glycemic control and decreased total calcium values when compared to controls (p < 0.05. For all the polymorphisms studied, the genotype and allele frequencies in patients with T1DM were not significantly different from the controls. In patients with T1DM, carriers of OPG 1181CC showed higher concentrations of ionized calcium compared to patients with GG+GC genotypes. These results suggest that low BMD is associated with poor glycemic control in T1DM. Despite the lack of a detected association between OPG polymorphisms and BMD in these patients, the increased ionized calcium in those carrying OPG 1181CC suggests a possible increase in osteoclastogenesis, a conclusion that may be supported by the lower BMD observed in these subjects.

[Interaction between HLA-DRB1 gene polymorphism and environmental risk factors in the development of gestational diabetes mellitus].

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Wang, Ming; Zhang, Li; Liu, Xinghui

2014-04-01

To explore the interactions between human leukocyte antigen (HLA) -DRB1 gene polymorphism and environmental risk factors in gestational diabetes mellitus (GDM) pathogenesis. Pregnant women who had prenatal cares in Obstetric Department, West China Second Hospital of Sichuan University were recruited from January 1(st) to December 31(st) in 2011. A prospective cohort study was conducted in the women who had a glucose challenge test (GCT) or 75 g oral glucose tolerance test (OGTT) during 24-28 gestational weeks. A total of 104 women diagnosed with GDM were randomly included in GDM group while another 103 normal women fell into the control group. The HLA-DRB1 polymorphism was detected by Polymerase Chain Reaction - Sequence Specific Primers (PCR-SSP) method in both groups. The interactions between HLA-DRB1 polymorphism and environmental risk factors were analyzed based on the simple-case-study method. (1) There were 712 pregnant women with complete perinatal information during January 1(st) to December 31(st) , 2011, among whom 175 (24.6%) women were diagnosed with GDM. A logistic regression analysis showed that advanced maternal age (OR = 1.081, 95%CI: 1.027- 1.138), imbalanced diet (OR = 3.329, 95%CI: 2.167-5.116), high body mass index (BMI ≥ 24.0 kg/m(2)) before pregnancy (OR = 1.095, 95%CI:1.008-1.190), HBsAg carrier status (OR = 3.173, 95%CI: 1.387-7.260) and family history of diabetes mellitus (DM) (OR = 1.798, 95%CI: 1.063-3.041) were risk factors of GDM. (2) There were 49 HLA-DRB1 genotypes and 51 HLA-DRB1 genotypes in GDM group and the control group, respectively. We further compared the genotypes that occurred in over 3 cases in either group and found that HLA-DRB1*12, 16 was only detected in 5 cases (5/103, 4.9%) in control group, and the difference was significant between the two groups (P = 0.029). HLA-DRB1*11, 16 and HLA-DRB1*09,09 were only detected in 4 cases (3.8%, 4/104) and 5 cases (4.8%, 5/104) in GDM group respectively, but without significant

STAT3 polymorphism and Helicobacter pylori CagA strains with higher number of EPIYA-C segments independently increase the risk of gastric cancer

International Nuclear Information System (INIS)

Rocha, Gifone A; Rocha, Andreia MC; Gomes, Adriana D; Faria, César LL Jr; Melo, Fabrício F; Batista, Sérgio A; Fernandes, Viviane C; Almeida, Nathálie BF; Teixeira, Kádima N; Brito, Kátia S; Queiroz, Dulciene Maria Magalhães

2015-01-01

Because to date there is no available study on STAT3 polymorphism and gastric cancer in Western populations and taking into account that Helicobacter pylori CagA EPIYA-C segment deregulates SHP-2/ERK-JAK/STAT3 pathways, we evaluated whether the two variables are independently associated with gastric cancer. We included 1048 subjects: H. pylori-positive patients with gastric carcinoma (n = 232) and with gastritis (n = 275) and 541 blood donors. Data were analyzed using logistic regression model. The rs744166 polymorphic G allele (p = 0.01; OR = 1.76; 95 % CI = 1.44-2.70), and CagA-positive (OR = 12.80; 95 % CI = 5.58-19.86) status were independently associated with gastric cancer in comparison with blood donors. The rs744166 polymorphism (p = 0.001; OR = 1.64; 95 % CI = 1.16-2.31) and infection with H. pylori CagA-positive strains possessing higher number of EPIYA-C segments (p = 0.001; OR = 2.28; 95 % CI = 1.41-3.68) were independently associated with gastric cancer in comparison with gastritis. The association was stronger when host and bacterium genotypes were combined (p < 0.001; OR = 3.01; 95 % CI = 2.29-3.98). When stimulated with LPS (lipopolysaccharide) or Pam3Cys, peripheral mononuclear cells of healthy carriers of the rs744166 GG and AG genotypes expressed higher levels of STAT3 mRNA than those carrying AA genotype (p = 0.04 for both). The nuclear expression of phosphorylated p-STAT3 protein was significantly higher in the antral gastric tissue of carriers of rs744166 GG genotype than in carriers of AG and AA genotypes. Our study provides evidence that STAT3 rs744166 G allele and infection with CagA-positive H. pylori with higher number of EPIYA-C segments are independent risk factors for gastric cancer. The odds ratio of having gastric cancer was greater when bacterium and host high risk genotypes were combined

The functional polymorphism rs73598374:G>A (p.Asp8Asn) of the ADA gene is associated with telomerase activity and leukocyte telomere length.

Science.gov (United States)

Concetti, Fabio; Carpi, Francesco M; Nabissi, Massimo; Picciolini, Matteo; Santoni, Giorgio; Napolioni, Valerio

2015-02-01

Recent evidence demonstrated a relevant role of adenosine deaminase (ADA) in replicative senescence of T cells through its capacity to modulate telomerase activity (TA). Herein, we tested the impact of the functional polymorphism ADA rs73598374:G>A (c.22G>A, p.Asp8Asn) on telomere biology, by measuring TA and leukocyte telomere length (LTL) in healthy subjects selected according to rs73598374 genotype. rs73598374-A carriers showed lower TA (P=0.019) and shorter LTL (P=0.003), respectively, compared to G/G carriers. rs73598374-A carriers showed a stronger cross-sectional age reduction of LTL (r=-0.314, P=0.005) compared to G/G carriers (r=-0.243, P=0.022). The reduced ADA activity associated to rs73598374-A variant predisposes those carriers to display higher levels of adenosine compared to G/G carriers. Consequently, it may lead to an accelerated process of replicative senescence, causing a stronger reduction of TA and in turn shorter LTL. In conclusion, the crucial role played by replicative senescence of the immune system in several human diseases and in the aging process underscores the relevance of the present findings and also spurs interest into the possible involvement of rs73598374 in shaping the susceptibility to several age-related diseases.

Trp64Arg polymorphism of the ADRB3 gene associated with maximal fat oxidation and LDL-C levels in non-obese adolescents.

Science.gov (United States)

Jesus, Íncare Correa de; Alle, Lupe Furtado; Munhoz, Eva Cantalejo; Silva, Larissa Rosa da; Lopes, Wendell Arthur; Tureck, Luciane Viater; Purim, Katia Sheylla Malta; Titski, Ana Claudia Kapp; Leite, Neiva

2017-09-21

To analyze the association between the Trp64Arg polymorphism of the ADRB3 gene, maximal fat oxidation rates and the lipid profile levels in non-obese adolescents. 72 schoolchildren, of both genders, aged between 11 and 17 years, participated in the study. The anthropometric and body composition variables, in addition to total cholesterol, HDL-c, LDL-c, triglycerides, insulin, and basal glycemia, were evaluated. The sample was divided into two groups according to the presence or absence of the polymorphism: non-carriers of the Arg64 allele, i.e., homozygous (Trp64Trp: n=54), and carriers of the Arg64 allele (Trp64Arg+Arg64Arg: n=18), in which the frequency of the Arg64 allele was 15.2%. The maximal oxygen uptake and peak of oxygen uptake during exercise were obtained through the symptom-limited, submaximal treadmill test. Maximal fat oxidation was determined according to the ventilatory ratio proposed in Lusk's table. Adolescents carrying the less frequent allele (Trp64Arg and Arg64Arg) had higher LDL-c levels (p=0.031) and lower maximal fat oxidation rates (p=0.038) when compared with non-carriers (Trp64Trp). Although the physiological processes related to lipolysis and lipid metabolism are complex, the presence of the Arg 64 allele was associated with lower rates of FATMAX during aerobic exercise, as well as with higher levels of LDL-c in adolescents. Copyright © 2017 Sociedade Brasileira de Pediatria. Published by Elsevier Editora Ltda. All rights reserved.

Brain-derived neurotrophic factor Val66Met polymorphism and dexamethasone/CRH test results in depressed patients.

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Schüle, Cornelius; Zill, Peter; Baghai, Thomas C; Eser, Daniela; Zwanzger, Peter; Wenig, Nadine; Rupprecht, Rainer; Bondy, Brigitta

2006-09-01

Data suggest that both neurotrophic and hypothalamic-pituitary-adrenocortical (HPA) systems are involved in the pathophysiology of depression. The aim of the present study was to investigate whether the non-conservative brain-derived neurotrophic factor (BDNF) Val66Met polymorphism has an impact on HPA axis activity in depressed patients. At admission, the dexamethasone/CRH (DEX/CRH) test was performed in 187 drug-free in-patients suffering from major depression or depressed state of bipolar disorder (DSM-IV criteria). Moreover, genotyping of BDNF Val66Met polymorphism was carried out using the fluorescence resonance energy transfer method (FRET). Homozygous carriers of the Met/Met genotype showed a significantly higher HPA axis activity during the DEX/CRH test than patients carrying the Val/Val or Val/Met genotype (ACTH, cortisol). Our results further contribute to the hypothesized association between HPA axis dysregulation and reduced neuroplasticity in depression and are consistent with the assumption that BDNF is a stress-responsive intercellular messenger modifying HPA axis activity.

Glucose tolerance, insulin sensitivity and insulin release in European non-diabetic carriers of a polymorphism upstream of CDKN2A and CDKN2B

DEFF Research Database (Denmark)

Hribal, M L; Presta, I; Procopio, T

2011-01-01

The aim of this study was to investigate the association of the rs10811661 polymorphism near the CDKN2B/CDKN2A genes with glucose tolerance, insulin sensitivity and insulin release in three samples of white people with European ancestry.......The aim of this study was to investigate the association of the rs10811661 polymorphism near the CDKN2B/CDKN2A genes with glucose tolerance, insulin sensitivity and insulin release in three samples of white people with European ancestry....

A Pilot Study Evaluating the Contribution of SLC19A1 (RFC-1 80G>A Polymorphism to Alzheimer’s Disease in Italian Caucasians

Directory of Open Access Journals (Sweden)

Fabio Coppedè

2014-01-01

Full Text Available Alzheimer’s disease (AD is the most common neurodegenerative disorder and the primary form of dementia in the elderly. Polymorphisms of genes involved in folate metabolism have been frequently suggested as risk factors for sporadic AD. A common c.80G>A polymorphism (rs1051266 in the gene coding for the reduced folate carrier (SLC19A1 gene, commonly known as RFC-1 gene was investigated as AD risk factor in Asian populations, yielding conflicting results. We screened a Caucasian population of Italian origin composed of 192 sporadic AD patients and 186 healthy matched controls, for the presence of the RFC-1 c.80G>A polymorphism, and searched for correlation with circulating levels of folate, homocysteine, and vitamin B12. No difference in the distribution of allele and genotype frequencies was observed between AD patients and controls. No correlation was observed among the genotypes generated by the RFC-1 c.80G>A polymorphism and circulating levels of folate, homocysteine, and vitamin B12 either in the whole cohort of subjects or after stratification into clinical subtypes. Present results do not support a role for the RFC-1 c.80G>A polymorphism as independent risk factor for sporadic AD in Italian Caucasians.

Association between -308 G/A TNF-α polymorphism and appendicular skeletal muscle mass index as a marker of sarcopenia in normal weight obese syndrome.

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Di Renzo, L; Sarlo, F; Petramala, L; Iacopino, L; Monteleone, G; Colica, C; De Lorenzo, A

2013-01-01

Normal weight obese (NWO) syndrome is characterized by normal body mass index (BMI), but high amount of fat mass and reduced lean mass. We evaluated allelic frequency of the G/A -308 TNF-α polymorphism and prevalence of sarcopenia in NWO. We enrolled 120 Italian healthy women, distinguished into 3 groups: normal weight (NW); NWO, and preobese-obese (PreOB/OB) and evaluated anthropometric parameters, body composition by dual X-ray absorptiometry, blood tests, and genotyping of G/A -308 TNF-α polymorphism. We found a positive association between sarcopenic obesity and -308 TNF-α polymorphism. All obese women were sarcopenic and were no carrier of mutation (G/G). Among all G/G, NWO showed significant differences in lean mass and total body lean mass (TBLean) with respect to NW and PreOB/OB (P skeletal muscle mass index values, 4.21% of NW were sarcopenic (50% G/G and 50% G/A); the same percentage was observed in NWO subjects (100% G/G). Moreover, 2.10% of PreOB/OB were sarcopenic and all were G/G. Our study suggests that TNF-α polymorphism contributes to sarcopenic obesity susceptibility, in association with body composition. This is the first study that shows the importance of TNF-α polymorphism to determine TBLean variation in NWO syndrome.

Effects of the BDNF Val66Met polymorphism and met allele load on declarative memory related neural networks.

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Dodds, Chris M; Henson, Richard N; Suckling, John; Miskowiak, Kamilla W; Ooi, Cinly; Tait, Roger; Soltesz, Fruzsina; Lawrence, Phil; Bentley, Graham; Maltby, Kay; Skeggs, Andrew; Miller, Sam R; McHugh, Simon; Bullmore, Edward T; Nathan, Pradeep J

2013-01-01

It has been suggested that the BDNF Val66Met polymorphism modulates episodic memory performance via effects on hippocampal neural circuitry. However, fMRI studies have yielded inconsistent results in this respect. Moreover, very few studies have examined the effect of met allele load on activation of memory circuitry. In the present study, we carried out a comprehensive analysis of the effects of the BDNF polymorphism on brain responses during episodic memory encoding and retrieval, including an investigation of the effect of met allele load on memory related activation in the medial temporal lobe. In contrast to previous studies, we found no evidence for an effect of BDNF genotype or met load during episodic memory encoding. Met allele carriers showed increased activation during successful retrieval in right hippocampus but this was contrast-specific and unaffected by met allele load. These results suggest that the BDNF Val66Met polymorphism does not, as previously claimed, exert an observable effect on neural systems underlying encoding of new information into episodic memory but may exert a subtle effect on the efficiency with which such information can be retrieved.

Effects of the BDNF Val66Met polymorphism and met allele load on declarative memory related neural networks.

Directory of Open Access Journals (Sweden)

Chris M Dodds

Full Text Available It has been suggested that the BDNF Val66Met polymorphism modulates episodic memory performance via effects on hippocampal neural circuitry. However, fMRI studies have yielded inconsistent results in this respect. Moreover, very few studies have examined the effect of met allele load on activation of memory circuitry. In the present study, we carried out a comprehensive analysis of the effects of the BDNF polymorphism on brain responses during episodic memory encoding and retrieval, including an investigation of the effect of met allele load on memory related activation in the medial temporal lobe. In contrast to previous studies, we found no evidence for an effect of BDNF genotype or met load during episodic memory encoding. Met allele carriers showed increased activation during successful retrieval in right hippocampus but this was contrast-specific and unaffected by met allele load. These results suggest that the BDNF Val66Met polymorphism does not, as previously claimed, exert an observable effect on neural systems underlying encoding of new information into episodic memory but may exert a subtle effect on the efficiency with which such information can be retrieved.

Associations of recurrent miscarriages with chromosomal abnormalities, thrombophilia allelic polymorphisms and/or consanguinity in Saudi Arabia.

Science.gov (United States)

Turki, Rola F; Assidi, Mourad; Banni, Huda A; Zahed, Hanan A; Karim, Sajjad; Schulten, Hans-Juergen; Abu-Elmagd, Muhammad; Rouzi, Abdulrahim A; Bajouh, Osama; Jamal, Hassan S; Al-Qahtani, Mohammed H; Abuzenadah, Adel M

2016-10-10

Recurrent pregnancy loss (RPL) or recurrent spontaneous abortion is an obstetric complication that affects couples at reproductive age. Previous reports documented a clear relationship between parents with chromosomal abnormalities and both recurrent miscarriages and infertility. However, limited data is available from the Arabian Peninsula which is known by higher rates of consanguineous marriages. The main goal of this study was to determine the prevalence of chromosomal abnormalities and thrombophilic polymorphisms, and to correlate them with RPL and consanguinity in Saudi Arabia. Cytogenetic analysis of 171 consent patients with RPL was performed by the standard method of 72-h lymphocyte culture and GTG banding. Allelic polymorphisms of three thrombophilic genes (Factor V Leiden, Prothrombin A20210G, MTHFR C677T) were performed using PCR-RFLP (restriction fragment length polymorphism) and gel electrophoresis. Data analysis revealed that 7.6 % of patients were carrier of numerical or structural chromosomal abnormalities. A high rate of translocations (46 %) was associated to increased incidence of RPL. A significant correlation between consanguineous RPL patients and chromosomal abnormalities (P consanguineous marriages in the Saudi population, these results underline the importance of systematic cytogenetic investigation and genetic counseling preferably at the premarital stage or at least during early pregnancy phase through preimplantation genetic diagnosis (PGD).

Malaria severity: Possible influence of the E670G PCSK9 polymorphism: A preliminary case-control study in Malian children.

Science.gov (United States)

Arama, Charles; Diarra, Issa; Kouriba, Bourèma; Sirois, Francine; Fedoryak, Olesya; Thera, Mahamadou A; Coulibaly, Drissa; Lyke, Kirsten E; Plowe, Christopher V; Chrétien, Michel; Doumbo, Ogobara K; Mbikay, Majambu

2018-01-01

Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) is a hepatic secretory protein which promotes the degradation of low-density lipoprotein receptors leading to reduced hepatic uptake of plasma cholesterol. Non-synonymous single-nucleotide polymorphisms in its gene have been linked to hypo- or hyper- cholesterolemia, depending on whether they decrease or increase PCSK9 activity, respectively. Since the proliferation and the infectivity of Plasmodium spp. partially depend on cholesterol from the host, we hypothesize that these PCSK9 genetic polymorphisms could influence the course of malaria infection in individuals who carry them. Here we examined the frequency distribution of one dominant (C679X) and two recessive (A443T, I474V) hypocholesterolemic polymorphisms as well as that of one recessive hypercholesterolemic polymorphism (E670G) among healthy and malaria-infected Malian children. Dried blood spots were collected in Bandiagara, Mali, from 752 age, residence and ethnicity-matched children: 253 healthy controls, 246 uncomplicated malaria patients and 253 severe malaria patients. Their genomic DNA was extracted and genotyped for the above PCSK9 polymorphisms using Taqman assays. Associations of genotype distributions and allele frequencies with malaria were evaluated. The minor allele frequency of the A443T, I474V, E670G, and C679X polymorphisms in the study population sample was 0.12, 0.20, 0.26, and 0.02, respectively. For each polymorphism, the genotype distribution among the three health conditions was statistically insignificant, but for the hypercholesterolemic E670G polymorphism, a trend towards association of the minor allele with malaria severity was observed (P = 0.035). The association proved to be stronger when allele frequencies between healthy controls and severe malaria cases were compared (Odd Ratio: 1.34; 95% Confidence Intervals: 1.04-1.83); P = 0.031). Carriers of the minor allele of the E670G PCSK9 polymorphism might be more susceptible

Associations of the interleukin-1 gene locus polymorphisms with risk to hip and knee osteoarthritis: gender and subpopulation differences.

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Kaarvatn, M H; Jotanovic, Z; Mihelic, R; Etokebe, G E; Mulac-Jericevic, B; Tijanic, T; Balen, S; Sestan, B; Dembic, Z

2013-02-01

Genetic predisposition to the complex hereditary disease like osteoarthritis (OA) of the large joints (hip and knee) includes the interleukin-1 gene (IL-1) cluster on chromosome 2. Using a case-control study with 500 OA patients (240 knee and 260 hip OA patients, all with joint replacement), we analysed frequencies of IL-1 gene cluster polymorphisms in Croatian Caucasian population. The control samples came from 531 healthy individuals including blood donors. We genotyped two single nucleotide polymorphisms in the IL-1 gene locus at IL-1A (-889, C>T, rs1800587) and IL-1B (+3594, C>T, rs1143634) and compared their frequencies between patients and controls. We predicted haplotypes by combining current data with our previous results on gene polymorphisms (IL-1B, rs16944 and the IL-1 receptor antagonist gene [IL-1RN] variable number tandem repeat [VNTR]) for the same population. Haplotype analyses revealed gender disparities and showed that women carriers of the 1-2-1-1 haplotype [IL-1A(rs1800587) - IL-1B(rs1143634) - IL-1B(rs16944) - IL-1RN(VNTR)] had sixfold lower risk to develop knee OA. However, carriers of the 1-1-1-2 haplotype of both sexes had over twofold higher predisposition to hip OA. Our results differ from some earlier studies in Caucasian subpopulations, which may be due to the fact that this is the first study to separate genders in assessing the IL-1-locus genetic risk of OA. The results suggest that inflammatory mediators like IL-1 might be implicated in the pathogenesis of primary OA in large joints and that as yet unidentified gender-specific factors exist in a Croatian Caucasian population. © 2012 The Authors. Scandinavian Journal of Immunology © 2012 Blackwell Publishing Ltd.

[A protective effect of GLY272SER polymorphism of GNB3 gene in development of essential hypertension and its relations with environmental hypertension risk factors].

Science.gov (United States)

Polonikov, A V; Solodilova, M A; Ivanov, V P; Shestakov, A M; Ushachev, D V; Vialykh, E K; Vasil'eva, O V; Poliakova, N V; Antsupov, V V; Kabanina, V A; Kupriianova, Ia S; Bulgakova, I V; Kozhukhov, M A; Tevs, D S

2011-01-01

To study associations of C825T (rs5443) and G272S (rs16932941) polymorphisms of GNB3 gene in Russian population of the Central Chernozem region with essential hypertension (EH) risk; to elicit the role of environmental risk factors in realization of EH predisposition in this gene genotypes carriers. We studied DNA samples obtained from 205 EH patients and 207 healthy individuals. EH patients were treated in Kursk hospitals. Genotyping of GNB3 gene polymorphisms was conducted by polymerase chain reaction and restriction analysis. Prevalence of 82ST allele of GNB3 gene in EH patients and healthy individual was 0.334 and 0.295, respectively, of 272S allele--0.037 and 0.058, respectively. We found no significant differences by prevalence of genotypes of gene GNB3 polymorphisms C825T and G272S in EH patients and healthy individuals. Non-smoking carriers of 272GS genotype had a low risk of EH (OR 0.42 in 95% CI from 0.18 to 0.97; p = 0.04). Smokers had no protective effect of this genotype. The protective effect of 272GS genotype was also found in individuals with low or moderate alcohol drinking habits (OR 0.29 in 95% CI from 0.11 to 0.77, p = 0.02) and in individuals without chronic exposure to stress (OR 0.29 in 95% CI from 0.09 to 0.91, p = 0.04). In contrast, hard drinkers and patients exposed to chronic stress had no protective effect of heterozygous genotype 272GS of gene GNB3. G272S polymorphism of GNB3 gene can be considered as a new genetic marker of predisposition to EH. The protective effect depends of environmental factors associated with high risk to develop EH.

Association between paraoxonase-1 gene Q192R and L55M polymorphisms in systemic lupus erythematosus (SLE) and anti-phospholipid syndrome (APS) in a population from Cairo of Egypt.

Science.gov (United States)

Ibrahim, Alshaymaa Ahmed; El-Lebedy, Dalia; Ashmawy, Ingy; Hady, Maha Abdel

2017-06-01

Paraoxonase-1 (PON1) is involved in the oxidative stress process that cause tissue damage observed in systemic lupus erythematosus (SLE) and anti-phospholipid syndrome (APS). The aim of the present study was to investigate the association of PON1 Q192R and L55M polymorphisms with risk of SLE and associated APS among Egyptian sample. The study included 120 SLE patients (45 without APS and 75 with APS) and 120 healthy subjects. PON1 Q192R and L55M polymorphisms were genotyped by real-time PCR. No significant differences in Q192R genotypes or allele frequencies were found between patients and controls (p = 0.5 and 0.1, respectively). The frequency of the 55M allele was significantly higher in SLE patients than in controls (66.6 vs. 43.3%), while the 55L allele was more frequent in controls (56.6%) than in patients (33.3%) (p = 0.03). The LL genotype was more frequent in controls (21.6%) than in patients (10%) while M allele carrier genotypes (LM + MM) were more frequent among patients (90%) than controls (78.3%), p = 0.04. Also, the 55M allele was more frequent in APS patients (73.3%) than in patients without APS (55.6%), p = 0.004. M allele carrier genotypes (LM + MM) was significantly higher among APS patients (95.4%) than in non-APS patients (80%), p = 0.008. Our results indicated that the PON1 L55M polymorphism associated with SLE and associated APS in a population from Cairo of Egypt, while the Q192R polymorphism plays no role in disease susceptibility. A large scale study to assess PON1 polymorphisms, PON1 activity, and markers of oxidative stress interaction is needed to clarify the role of PON-1 polymorphisms in the pathogenesis of SLE and associated APS.

Effect of tryptophan hydroxylase gene polymorphism on aggression in major depressive disorder and undifferentiated somatoform disorder.

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Koh, Kyung Bong; Kim, Chan Hyung; Choi, Eun Hee; Lee, Young-joon; Seo, Won Youl

2012-05-01

Aggression and anger have been linked with depression, and anger suppression has been linked with somatic symptoms of somatoform disorders. However, the relationship between aggression or anger and genes in patients with depression and somatoform disorders has not been clearly elucidated. The objective of this study was to examine the effect of serotonin-related gene polymorphism on aggression in depressive disorders and somatoform disorders. A serotonin-related polymorphic marker was assessed by using single nucleotide polymorphism (SNP) genotyping. 106 outpatients with major depressive disorder (MDD), 102 outpatients with undifferentiated somatoform disorder, and 133 healthy subjects were enrolled between October 2005 and May 2008. Diagnoses were made according to the Korean version of the Structured Clinical Interview Schedule for DSM-IV. The allele and genotype frequencies of tryptophan hydroxylase-1 (TPH1) A218C were compared between groups. The Hamilton Depression Rating Scale and the Aggression Questionnaire were used for psychological assessment. Each of the 2 disorder groups scored significantly higher on all the Aggression Questionnaire subscales and on the total Aggression Questionnaire score than the healthy subjects (P sex and age. However, no significant differences were found in TPH1 C allele and CC homozygote frequencies between the undifferentiated somatoform disorder patients and the healthy subjects. TPH1 CC homozygote in the MDD group scored significantly higher in terms of verbal aggression (P = .03) and total Aggression Questionnaire score (P = .04) than A-carrier genotypes, regardless of sex and age. However, no significant differences were found in the scores of all the Aggression Questionnaire subscales and the total Aggression Questionnaire score between TPH1 CC homozygote and A-carrier genotypes in the undifferentiated somatoform disorder group and the control group, respectively. Aggression in MDD patients is more susceptible to an

Gene polymorphisms and the risk of warfarin-induced bleeding complications at therapeutic international normalized ratio (INR)

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Pourgholi, Leyla [Department of Pathology and Laboratory Medicine, Tehran Heart Center, Tehran University of Medical Sciences, P.O. Box 1411713138, Tehran (Iran, Islamic Republic of); Department of Pharmacology & Toxicology, School of Pharmacy, Kerman University of Medical Sciences, P.O. Box 7616911319, Kerman (Iran, Islamic Republic of); Goodarzynejad, Hamidreza [Department of Cardiac Research, Tehran Heart Center, Tehran University of Medical Sciences, P.O. Box 1411713138, Tehran (Iran, Islamic Republic of); Mandegary, Ali [Department of Pharmacology & Toxicology, School of Pharmacy, Kerman University of Medical Sciences, P.O. Box 7616911319, Kerman (Iran, Islamic Republic of); Gastroenterology and Hepatology Research Center, Afzalipour' s Hospital, Imam Highway, P.O. Box 7616913911, Kerman (Iran, Islamic Republic of); Ziaee, Shayan [Department of Pathology and Laboratory Medicine, Tehran Heart Center, Tehran University of Medical Sciences, P.O. Box 1411713138, Tehran (Iran, Islamic Republic of); Talasaz, Azita Hajhosseini [Department of Cardiac Research, Tehran Heart Center, Tehran University of Medical Sciences, P.O. Box 1411713138, Tehran (Iran, Islamic Republic of); Department of Clinical Pharmacy, School of Pharmacy, Tehran University of Medical Sciences (Iran, Islamic Republic of); Jalali, Arash [Department of Cardiac Research, Tehran Heart Center, Tehran University of Medical Sciences, P.O. Box 1411713138, Tehran (Iran, Islamic Republic of); Boroumand, Mohammadali, E-mail: maboroumand@yahoo.com [Department of Pathology and Laboratory Medicine, Tehran Heart Center, Tehran University of Medical Sciences, P.O. Box 1411713138, Tehran (Iran, Islamic Republic of)

2016-10-15

Background: Bleeding episodes commonly occur in patients on warfarin treatment even in those within therapeutic range of international normalized ratio (INR). The objective of this study was to investigate the effects of the 8 examined polymorphisms on the risk of bleeding complications in a sample of Iranian patients. Methods: A total of 552 warfarin treated patients who maintained on a target INR level of 2.0–3.5 for at least three consecutive intervals were enrolled from those attended our anticoagulation clinics. Ninety-two bleeding events were observed in 87 patients. The presences of the examined polymorphisms were analyzed using polymerase chain reaction-based restriction fragment length polymorphism (PCR-RFLP). Results: Patients with the T allele in NQO1*2 (CT or TT genotypes) had a higher risk of bleeding than patients with the CC genotype (adjusted OR: 2.25, 95% CI: 1.37 to 3.70, P = 0.001). Those who were carriers of CYP2C9 one-variant haplotypes (*1/*2 or *1/*3) were also found to be associated with the higher risk of bleeding events. Compared to reference group (*1/*1), the odds of bleeding increased for carriers of one variant allele (*1/*2 or *1/*3) (adjusted OR: 1.75, 95% CI: 1.03 to 2.97, P = 0.039). Variant VKORC1, Factor VII, and EPHX1 genotypes were not significantly associated with the risk of bleeding events. Conclusion: The SNP C609T within NQO1 and haplotypes of CYP2C9 (1*2 or 1*3) are independently associated to bleeding complications of warfarin at normal INR. Further studies are required to confirm such associations in diverse racial and ethnic populations. - Highlights: • NQO1 C609T variant is associated with warfarin induced bleeding at therapeutic INR. • Haplotypes of CYP2C9 (1*2 or 1*3) are also associated with bleeding events. • VKORC1, Factor VII, and EPHX1 genotypes were not associated with bleeding risk.

Gene polymorphisms and the risk of warfarin-induced bleeding complications at therapeutic international normalized ratio (INR)

International Nuclear Information System (INIS)

Pourgholi, Leyla; Goodarzynejad, Hamidreza; Mandegary, Ali; Ziaee, Shayan; Talasaz, Azita Hajhosseini; Jalali, Arash; Boroumand, Mohammadali

2016-01-01

Background: Bleeding episodes commonly occur in patients on warfarin treatment even in those within therapeutic range of international normalized ratio (INR). The objective of this study was to investigate the effects of the 8 examined polymorphisms on the risk of bleeding complications in a sample of Iranian patients. Methods: A total of 552 warfarin treated patients who maintained on a target INR level of 2.0–3.5 for at least three consecutive intervals were enrolled from those attended our anticoagulation clinics. Ninety-two bleeding events were observed in 87 patients. The presences of the examined polymorphisms were analyzed using polymerase chain reaction-based restriction fragment length polymorphism (PCR-RFLP). Results: Patients with the T allele in NQO1*2 (CT or TT genotypes) had a higher risk of bleeding than patients with the CC genotype (adjusted OR: 2.25, 95% CI: 1.37 to 3.70, P = 0.001). Those who were carriers of CYP2C9 one-variant haplotypes (*1/*2 or *1/*3) were also found to be associated with the higher risk of bleeding events. Compared to reference group (*1/*1), the odds of bleeding increased for carriers of one variant allele (*1/*2 or *1/*3) (adjusted OR: 1.75, 95% CI: 1.03 to 2.97, P = 0.039). Variant VKORC1, Factor VII, and EPHX1 genotypes were not significantly associated with the risk of bleeding events. Conclusion: The SNP C609T within NQO1 and haplotypes of CYP2C9 (1*2 or 1*3) are independently associated to bleeding complications of warfarin at normal INR. Further studies are required to confirm such associations in diverse racial and ethnic populations. - Highlights: • NQO1 C609T variant is associated with warfarin induced bleeding at therapeutic INR. • Haplotypes of CYP2C9 (1*2 or 1*3) are also associated with bleeding events. • VKORC1, Factor VII, and EPHX1 genotypes were not associated with bleeding risk.

Sealed substrate carrier for electroplating

Science.gov (United States)

Ganti, Kalyana Bhargava [Fremont, CA

2012-07-17

One embodiment relates to a substrate carrier for use in electroplating a plurality of substrates. The substrate carrier includes a non-conductive carrier body on which the substrates are held, and conductive lines are embedded within the carrier body. A conductive bus bar is embedded into a top side of the carrier body and is conductively coupled to the conductive lines. A thermoplastic overmold covers a portion of the bus bar, and there is a plastic-to-plastic bond between the thermoplastic overmold and the non-conductive carrier body. Other embodiments, aspects and features are also disclosed.

Study of the Bulk Charge Carrier Dynamics in Anatase and Rutile TiO2 Single Crystals by Femtosecond Time Resolved Spectroscopy

KAUST Repository

Maity, Partha

2018-04-02

Understanding of the fundamentals behind charge carriers of photo-catalytic materials are still illusive hindering progress in our quest for renewable energy. TiO2 anatase and rutile are the most understood phases in photo-catalysis and serve as the best model for fundamental studies. Their ultrafast charge carrier dynamics especially on TiO2 anatase single crystal (the most active phase) are unresolved. Here femtosecond time resolved spectroscopy (TRS) was carried out to explore the dynamics of photo-excited charge carriers’ recombination in anatase single crystal, for the first time using pump fluence effects, and compares it to that of the rutile single crystal. A significant difference in charge carrier recombination rates between both crystals is observed. We found that the time constants for carrier recombination are two orders of magnitude slower for anatase (101) when compared to those of rutile (110). Moreover, bulk defects introduced by reduction of the samples via annealing in ultra-high vacuum resulted in faster recombination rates for both polymorphs. Both states (fresh and reduced) probed by pump fluence dependence measurements revealed that the major recombination channel in fresh and reduced anatase and reduced rutile is the first-order Shockley–Reed mediated. However, for fresh rutile, third-body Auger recombination was observed, attributed to the presence of higher density of intrinsic charge carriers. At all excitation wavelengths and fluence investigated, anatase (101) single crystal show longer charge carrier lifetime when compared to rutile (110) single. This may explain the superiority of the anatase phase for the electron transfer H+ reduction to molecular hydrogen.

[Influence of interleukin-1 beta gene polymorphism and childhood maltreatment on antidepressant treatment].

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Chen, Ying; Zhang, Zhijun; Xu, Zhi; Pu, Mengjia; Geng, Leiyu

2015-12-01

To explore the influence of interleukin-1 beta (IL1B) gene polymorphism and childhood maltreatment on antidepressant treatment. Two hundred and four patients with major depressive disorder (MDD) have received treatment with single antidepressant drugs and were followed up for 8 weeks. Hamilton depression scale-17 (HAMD-17) was used to evaluate the severity of depressive symptoms and therapeutic effect. Childhood maltreatment was assessed using Childhood Trauma Questionnaire, a 28-item Short Form (CTQ-SF). Single nucleotide polymorphism (SNP) of the IL1B gene was determined using a SNaPshot method. Correlation of rs16944 gene polymorphism with response to treatment was analyzed using Unphased 3.0.13 software. The main and interactive effects of SNP and childhood maltreatment on the antidepressant treatment were analyzed using Logistic regression analysis. No significant difference of gender, age, year of education, family history, episode time, and antidepressant agents was detected between the remitters and non-remitters. Association analysis has found that the SNP rs16944 in the IL1B AA genotype carriers antidepressant response was poorer (χ2=3.931, P=0.047). No significant difference was detected in the CTQ scores between the two groups. Genetic and environmental interaction analysis has demonstrated a significant correlation between rs16944 AA genotype and childhood maltreatment and poorer response to antidepressant treatment. The SNP rs16944 in the IL1B gene and its interaction with childhood maltreatment may influence the effect of antidepressant treatment for patients with MDD.

Association between Gene Polymorphisms and Pain Sensitivity Assessed in a Multi-Modal Multi-Tissue Human Experimental Model - An Explorative Study

DEFF Research Database (Denmark)

Nielsen, Lecia Møller; Olesen, Anne Estrup; Sato, Hiroe

2016-01-01

The genetic influence on sensitivity to noxious stimuli (pain sensitivity) remains controversial and needs further investigation. In the present study, the possible influence of polymorphisms in three opioid receptor (OPRM, OPRD and OPRK) genes and the catechol-O-methyltransferase (COMT) gene...... on pain sensitivity in healthy participants was investigated. Catechol-O-methyltransferase has an indirect effect on the mu opioid receptor by changing its activity through an altered endogenous ligand effect. Blood samples for genetic analysis were withdrawn in a multi-modal and multi-tissue experimental......, electrical and thermal visceral stimulations. A cold pressor test was also conducted. DNA was available from 38 of 40 participants. Compared to non-carriers of the COMT rs4680A allele, carriers reported higher bone pressure pain tolerance threshold (i.e. less pain) by up to 23.8% (p

Association Between ACE Gene Polymorphism and QT Dispersion in Patients with Acute Myocardial Infarction.

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Karahan, Zulkuf; Ugurlu, Murat; Ucaman, Berzal; Veysel Ulug, Ali; Kaya, Ilyas; Cevik, Kemal; Sahin Adiyaman, Mehmet; Oztürk, Onder; Iyem, Hikmet; Ozdemir, Ferit

2016-01-01

Angiotensin converting enzyme (ACE) gene polymorphism is associated with high renin-angiotensin system causing myocardial fibrosis and ventricular repolarization abnormality. Based on these findings, this study was designed to determine the association between ACE gene insertion/deletion (I/D) polymorphism and QT dispersion after acute myocardial infarction (MI). The study included 108 patients with acute MI. Blood samples were obtained from all the patients for genomic DNA analysis. ECGs were recorded at baseline and at the end of a 6-month follow up. The OT dispersion was manually calculated. The mean age of the patients was 57.5 ±9.9 years (ranging from 36 to 70). The patients with DD genotype showed longer QT dispersion than patients with II or DI genotype at the baseline, while at the end of the six-month follow up the patients with DI genotype showed longer QT dispersion than patients with DD or II genotypes. However, the magnitude of the QT dispersion prolongation was higher in patients carrying the ACE D allele than patients who were not carrying it, at baseline and at the end of six-month follow up (52.5 ±2.6 msn vs. 47.5±2.1 msn at baseline, 57±3.2 msn vs. 53±2.6 msn in months, P: 0.428 and P: 0.613, respectively). Carriers of the D allele of ACE gene I/D polymorphism may be associated with QT dispersion prolongation in patients with MI.An interaction of QT dispersion and ACE gene polymorphism may be associated with an elevation of serum type I-C terminal pro-collagen concentration, possibly leading to myocardial fibrosis, and increased action potential duration.

Carrier-carrier relaxation kinetics in quantum well semiconductor structures with nonparabolic energy bands

DEFF Research Database (Denmark)

Dery, H.; Tromborg, Bjarne; Eisenstein, G.

2003-01-01

We describe carrier-carrier scattering dynamics in an inverted quantum well structure including the nonparabolic nature of the valance band. A solution of the semiconductor Bloch equations yields strong evidence to a large change in the temporal evolution of the carrier distributions compared to ...

G16R single nucleotide polymorphism but not haplotypes of the ß2-adrenergic receptor gene alters cardiac output in humans

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Rokamp, Kim Z; Staalsø, Jonatan M; Gartmann, Martin

2013-01-01

Variation in genes encoding the ß2-adrenergic receptor (ADRB2) and angiotensin-converting enzyme (ACE) may influence Q¿ (cardiac output). The 46G>A (G16R) SNP (single nucleotide polymorphism) has been associated with ß2-mediated vasodilation, but the effect of ADRB2 haplotypes on Q¿ has not been...... studied. Five SNPs within ADRB2 (46G>A, 79C>G, 491C>T, 523C>A and 1053G>C by a pairwise tagging principle) and the I/D (insertion/deletion) polymorphism in ACE were genotyped in 143 subjects. Cardiovascular variables were evaluated by the Model flow method at rest and during incremental cycling exercise...... V¿O2 (oxygen uptake) in G16G subjects, but the increase was 0.5 (0.0-0.9) l/min lower in Arg16 carriers (P=0.035). A similar effect size was observed for the Arg16 haplotypes ACCCG and ACCCC. No interaction was found between ADRB2 and ACE polymorphisms. During exercise, the increase in Q¿ was 0...

Effect of the 5-HTTLPR polymorphism on posttraumatic stress disorder, depression, anxiety, and quality of life among Iraq and Afghanistan veterans.

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Kimbrel, Nathan A; Morissette, Sandra B; Meyer, Eric C; Chrestman, Roberta; Jamroz, Robert; Silvia, Paul J; Beckham, Jean C; Young, Keith A

2015-01-01

Posttraumatic stress disorder (PTSD), depression, anxiety, and stress are significant problems among returning veterans and are associated with reduced quality of life. A correlational design was used to examine the impact of a polymorphism (5-HTTLPR) in the serotonin transporter promoter gene on post-deployment adjustment among returning veterans. A total of 186 returning Iraq and Afghanistan veterans were genotyped for the 5-HTTLPR polymorphism. Symptoms of PTSD, depression, general stress, and anxiety were assessed along with quality of life. After controlling for combat exposure, age, sex of the participant, and race, 5-HTTLPR had a significant multivariate effect on post-deployment adjustment, such that S' carriers reported more post-deployment adjustment problems and worse quality of life than veterans homozygous for the L' allele. This effect was larger when the analyses were restricted to veterans of European ancestry. Our findings suggest that veterans who carry the S' allele of the 5-HTTLPR polymorphism may be at increased risk for adjustment problems and reduced quality of life following deployments to war zones.

Association of Polymorphous Markers Ala(-9Val of SOD2 Gene and C(-262T of CAT Gene in Patients with Hashimotos’ Thyroiditis and Hypothyroidism

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A Mkrtumyan

2008-03-01

Full Text Available A comparative analysis of distribution of alleles and genotypes of polymorphous markers Ala(-9Val of SOD2 gene and C(-262T of CAT gene was performed. Eighty six patients with Hashimotos’ thyroiditis (HT were enrolled in the study. Significant deferens were found by comparison of alleles and genotypes incidence of polymorphous marker Ala(-9Val of SOD2 gene in HT-patients and in control group. Significant increase of incidence of Val/Val genotype (OR = 15,6; p = 0.04 in HT-patients may reflect a higher risk of HT in Val/Val individuals. This hypothesis may be confirmed by increase of malonic dialdehyde and antithyroid antibodies in Val/Val carriers.

29 CFR 1201.1 - Carrier.

Science.gov (United States)

2010-07-01

... 29 Labor 4 2010-07-01 2010-07-01 false Carrier. 1201.1 Section 1201.1 Labor Regulations Relating to Labor (Continued) NATIONAL MEDIATION BOARD DEFINITIONS § 1201.1 Carrier. The term carrier includes any express company, sleeping car company, carrier by railroad, subject to the Interstate Commerce Act...

X-Ray Cross-Complementing Group 1 and Thymidylate Synthase Polymorphisms Might Predict Response to Chemoradiotherapy in Rectal Cancer Patients

International Nuclear Information System (INIS)

Lamas, Maria J.; Duran, Goretti; Gomez, Antonio; Balboa, Emilia; Anido, Urbano; Bernardez, Beatriz; Rana-Diez, Pablo; Lopez, Rafael; Carracedo, Angel; Barros, Francisco

2012-01-01

Purpose: 5-Fluorouracil–based chemoradiotherapy before total mesorectal excision is currently the standard treatment of Stage II and III rectal cancer patients. We used known predictive pharmacogenetic biomarkers to identify the responders to preoperative chemoradiotherapy in our series. Methods and Materials: A total of 93 Stage II-III rectal cancer patients were genotyped using peripheral blood samples. The genes analyzed were X-ray cross-complementing group 1 (XRCC1), ERCC1, MTHFR, EGFR, DPYD, and TYMS. The patients were treated with 225 mg/m 2 /d continuous infusion of 5-fluorouracil concomitantly with radiotherapy (50.4 Gy) followed by total mesorectal excision. The outcomes were measured by tumor regression grade (TRG) as a major response (TRG 1 and TRG 2) or as a poor response (TRG3, TRG4, and TRG5). Results: The major histopathologic response rate was 47.3%. XRCC1 G/G carriers had a greater probability of response than G/A carriers (odds ratio, 4.18; 95% confidence interval, 1.62–10.74, p = .003) Patients with polymorphisms associated with high expression of thymidylate synthase (2R/3G, 3C/3G, and 3G/3G) showed a greater pathologic response rate compared with carriers of low expression (odds ratio, 2.65; 95% confidence interval, 1.10–6.39, p = .02) No significant differences were seen in the response according to EGFR, ERCC1, MTHFR C 677 and MTHFR A 1298 expression. Conclusions: XRCC1 G/G and thymidylate synthase (2R/3G, 3C/3G, and 3G/3G) are independent factors of a major response. Germline thymidylate synthase and XRCC1 polymorphisms might be useful as predictive markers of rectal tumor response to neoadjuvant chemoradiotherapy with 5-fluorouracil.

X-Ray Cross-Complementing Group 1 and Thymidylate Synthase Polymorphisms Might Predict Response to Chemoradiotherapy in Rectal Cancer Patients

Energy Technology Data Exchange (ETDEWEB)

Lamas, Maria J., E-mail: mlamasd@yahoo.es [Oncology Pharmacy Unit, Complejo Hospitalario Universitario of Santiago (CHUS), Choupana S/N, Santiago de Compostela (Spain); Duran, Goretti [Oncology Pharmacy Unit, Complejo Hospitalario Universitario of Santiago (CHUS), Choupana S/N, Santiago de Compostela (Spain); Gomez, Antonio [Department of Oncology Radiotherapy, Complejo Hospitalario Universitario of Santiago (CHUS), Choupana S/N, Santiago de Compostela (Spain); Balboa, Emilia [Molecular Medicine Unit, Fundacion Publica Galega de Medicina Xenomica, Choupana S/N, Santiago de Compostela (Spain); Anido, Urbano [Department of Medical Oncology, Complejo Hospitalario Universitario of Santiago (CHUS), Choupana S/N, Santiago de Compostela (Spain); Bernardez, Beatriz [Oncology Pharmacy Unit, Complejo Hospitalario Universitario of Santiago (CHUS), Choupana S/N, Santiago de Compostela (Spain); Rana-Diez, Pablo [Molecular Medicine Unit, Fundacion Publica Galega de Medicina Xenomica, Choupana S/N, Santiago de Compostela (Spain); Lopez, Rafael [Department of Medical Oncology, Complejo Hospitalario Universitario of Santiago (CHUS), Choupana S/N, Santiago de Compostela (Spain); Carracedo, Angel; Barros, Francisco [Fundacion Publica Galega de Medicina Xenomica and Genomic Medicine Group-CIBERER, University of Santiago de Compostela, Calle San Fransisco S/N, Santiago de Compostela (Spain)

2012-01-01

Purpose: 5-Fluorouracil-based chemoradiotherapy before total mesorectal excision is currently the standard treatment of Stage II and III rectal cancer patients. We used known predictive pharmacogenetic biomarkers to identify the responders to preoperative chemoradiotherapy in our series. Methods and Materials: A total of 93 Stage II-III rectal cancer patients were genotyped using peripheral blood samples. The genes analyzed were X-ray cross-complementing group 1 (XRCC1), ERCC1, MTHFR, EGFR, DPYD, and TYMS. The patients were treated with 225 mg/m{sup 2}/d continuous infusion of 5-fluorouracil concomitantly with radiotherapy (50.4 Gy) followed by total mesorectal excision. The outcomes were measured by tumor regression grade (TRG) as a major response (TRG 1 and TRG 2) or as a poor response (TRG3, TRG4, and TRG5). Results: The major histopathologic response rate was 47.3%. XRCC1 G/G carriers had a greater probability of response than G/A carriers (odds ratio, 4.18; 95% confidence interval, 1.62-10.74, p = .003) Patients with polymorphisms associated with high expression of thymidylate synthase (2R/3G, 3C/3G, and 3G/3G) showed a greater pathologic response rate compared with carriers of low expression (odds ratio, 2.65; 95% confidence interval, 1.10-6.39, p = .02) No significant differences were seen in the response according to EGFR, ERCC1, MTHFR{sub C}677 and MTHFR{sub A}1298 expression. Conclusions: XRCC1 G/G and thymidylate synthase (2R/3G, 3C/3G, and 3G/3G) are independent factors of a major response. Germline thymidylate synthase and XRCC1 polymorphisms might be useful as predictive markers of rectal tumor response to neoadjuvant chemoradiotherapy with 5-fluorouracil.

Matrix Gla Protein Polymorphisms are Associated with Coronary Artery Calcification in Men

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Crosier, Michael D.; Booth, Sarah L.; Peter, Inga; Dawson-Hughes, Bess; Price, Paul A.; O’Donnell, Christopher J.; Hoffmann, Udo; Williamson, Matthew K.; Ordovas, Jose M.

2009-01-01

Summary Matrix Gla protein (MGP) is a key regulator of vascular calcification. Genetic variation at the MGP locus could modulate the development of coronary artery calcification (CAC). Our aim was to examine the cross-sectional association between MGP single nucleotide polymorphisms (SNPs) [rs1800802 (T-138C), rs1800801 (G-7A), and rs4236 (Ala102Thr)] and CAC. CAC was measured by multidetector computed tomography (MDCT), in older men and women of European descent, (n = 386; 60 to 80 y of age). Serum MGP was measured by radioimmunoassay. Linear, Tobit and Ordinal regression analyses all revealed that in men, homozygous carriers of the minor allele of rs1800802 , rs1800801 , or rs4236 (minor allele frequency: 21, 38, and 40%, respectively) were associated with a decreased quantity of CAC, relative to major allele carriers. This association was not found in women. Although genetic variation in MGP was associated with serum MGP concentrations, there were no associations between serum MGP and CAC. The results of this study suggest a role for MGP genetic variants in coronary atherosclerosis among men that is not reflected in serum MGP concentrations. PMID:19352064

Disentangling the effects of serotonin on risk perception: S-carriers of 5-HTTLPR are primarily concerned with the magnitude of the outcomes, not the uncertainty.

Science.gov (United States)

Millroth, Philip; Juslin, Peter; Eriksson, Elias; Agren, Thomas

2017-10-01

Serotonin signaling is vital for reward processing, and hence, also for decision-making. The serotonin transporter gene linked polymorphic region (5-HTTLPR) has been connected to decision making, suggesting that short-allele carriers (s) are more risk averse than long-allele homozygotes (ll). However, previous research has not identified if this occurs because s-carriers (i) are more sensitive to the uncertainty of the outcomes or (ii) are more sensitive to the magnitude of the outcomes. This issue was disentangled using a willingness-to-pay task, where the participants evaluated prospects involving certain gains, uncertain gains, and ambiguous gains. The results clearly favored the hypothesis that s-carriers react more to the magnitude of the outcomes. Self-reported measures of everyday risk-taking behavior also favored this hypothesis. We discuss how these results are in line with recent research on the serotonergic impact on reward processing. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

An impact of CYP3A4 *1B polymorphism on rifampicin metabolism

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H. O. Poludenko

2017-08-01

Full Text Available Until now, the enzyme systems responsible for biotransformation of the antituberculous drug rifampicin remain unknown. The aim of research was an investigation of the candidate enzymes involved in the biotransformation of rifampicin using the computer system PASS and an experimental study concerning the effect of the polymorphism of the biotransformation gene CYP3A4 *1B on the level of rifampicin in the blood of patients with pulmonary tuberculosis (РTB. The probability (Pa of certain pharmacological activity and the effect on putative enzyme systems of the human body of rifampicin has been calculated by the PASS method. Polymerase chain reaction revealed the polymorphism of the CYP3A4 *1B gene among healthy volunteers as well as patients with РTB. With a high degree of probability, according to PASS calculations, it was predicted that rifampicin undergo metabolism with the CYP3A4 enzyme - probability (Ra were 0.891. According to the genotype CYP3A4 *1B, 95.3% of the healthy donors carried a homozygous wild-type gene (i.e., had high enzymatic activity - AA genotype; the rest 4.7% - were carriers of the heterozygous AG genotype (moderate enzyme activity.The polymorphism of CYP3A4 *1B genotypes and alleles in the south-west of Ukraine was close to the results obtained in European countries. 91.4% and 8.6% of the patients with РTB had AA and AG genotype, correspondently. Thus, among the patients with РTB, the AG genotype was more often observed than among healthy volunteers. There was no significant difference in rifampicin concentration among РTB-patients concerning CYP3A4 * 1B polymorphism.

Association Between Genetic Polymorphisms in the XRCC1, XRCC3, XPD, GSTM1, GSTT1, MSH2, MLH1, MSH3, and MGMT Genes and Radiosensitivity in Breast Cancer Patients

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Mangoni, Monica; Bisanzi, Simonetta; Carozzi, Francesca; Sani, Cristina; Biti, Giampaolo; Livi, Lorenzo; Barletta, Emanuela; Costantini, Adele Seniori; Gorini, Giuseppe

2011-01-01

Purpose: Clinical radiosensitivity varies considerably among patients, and radiation-induced side effects developing in normal tissue can be therapy limiting. Some single nucleotide polymorphisms (SNPs) have been shown to correlate with hypersensitivity to radiotherapy. We conducted a prospective study of 87 female patients with breast cancer who received radiotherapy after breast surgery. We evaluated the association between acute skin reaction following radiotherapy and 11 genetic polymorphisms in DNA repair genes: XRCC1 (Arg399Gln and Arg194Trp), XRCC3 (Thr241Met), XPD (Asp312Asn and Lys751Gln), MSH2 (gIVS12-6T>C), MLH1 (Ile219Val), MSH3 (Ala1045Thr), MGMT (Leu84Phe), and in damage-detoxification GSTM1 and GSTT1 genes (allele deletion). Methods and Materials: Individual genetic polymorphisms were determined by polymerase chain reaction and single nucleotide primer extension for single nucleotide polymorphisms or by a multiplex polymerase chain reaction assay for deletion polymorphisms. The development of severe acute skin reaction (moist desquamation or interruption of radiotherapy due to toxicity) associated with genetic polymorphisms was modeled using Cox proportional hazards, accounting for cumulative biologically effective radiation dose. Results: Radiosensitivity developed in eight patients and was increased in carriers of variants XRCC3-241Met allele (hazard ratio [HR] unquantifiably high), MSH2 gIVS12-6nt-C allele (HR = 53.36; 95% confidence intervals [95% CI], 3.56-798.98), and MSH3-1045Ala allele (HR unquantifiably high). Carriers of XRCC1-Arg194Trp variant allele in combination with XRCC1-Arg399Gln wild-type allele had a significant risk of radiosensitivity (HR = 38.26; 95% CI, 1.19-1232.52). Conclusions: To our knowledge, this is the first report to find an association between MSH2 and MSH3 genetic variants and the development of radiosensitivity in breast cancer patients. Our findings suggest the hypothesis that mismatch repair mechanisms may be

The absence of an association between Interleukin 1β gene polymorphisms and recurrent aphthous stomatitis (RAS).

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Ślebioda, Zuzanna; Kowalska, Anna; Rozmiarek, Marta; Krawiecka, Ewa; Szponar, Elżbieta; Dorocka-Bobkowska, Barbara

2017-12-01

Recurrent aphthous stomatitis (RAS) is a chronic, ulcerative disease with a probable polygenic mode of inheritance and complex etiology with a strong immunological background. The aim of the present study was to determine the possible association between two single nucleotide polymorphisms (SNPs) of the IL-1β gene: IL-1β-511 T>C (rs16944) and IL-1β+3954C>T (rs1143634) and RAS susceptibility in a moderately large group of patients. One hundred and four patients with minor, major and herpetiform RAS and 75 healthy volunteers were genotyped at IL-1β-511 T>C (rs16944) and IL-1β+3954C>T (rs1143634) using the PCR-RFLP approach. The results were statistically analysed with chi-square test and test of difference between two rates of structure, with p<0.05 assumed to be a statistically significance level (Statistica 10, StatSoft ® , Kraków, Poland). There were no statistically significant differences in the genotype distribution for the IL-1β C[+3954]T polymorphism between the RAS and control groups. The frequency of IL-1β*T[-511]/*T[-511] homozygotes among the patients was significantly higher when compared to our study control (p<0.0347). The results after stratification into carriers and non-carriers of C and T alleles did not clearly indicate which SNP may be considered a risk factor for RAS. The genetic association between the studied SNPs of the IL-1β gene and RAS remains controversial and requires further investigation. Copyright © 2017 Elsevier Ltd. All rights reserved.

TGF-β1 modulates the homeostasis between MMPs and MMP inhibitors through p38 MAPK and ERK1/2 in highly invasive breast cancer cells

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Gomes, Luciana R; Terra, Letícia F; Wailemann, Rosângela AM; Labriola, Leticia; Sogayar, Mari C

2012-01-01

Metastasis is the main factor responsible for death in breast cancer patients. Matrix metalloproteinases (MMPs) and their inhibitors, known as tissue inhibitors of MMPs (TIMPs), and the membrane-associated MMP inhibitor (RECK), are essential for the metastatic process. We have previously shown a positive correlation between MMPs and their inhibitors expression during breast cancer progression; however, the molecular mechanisms underlying this coordinate regulation remain unknown. In this report, we investigated whether TGF-β1 could be a common regulator for MMPs, TIMPs and RECK in human breast cancer cell models. The mRNA expression levels of TGF-β isoforms and their receptors were analyzed by qRT-PCR in a panel of five human breast cancer cell lines displaying different degrees of invasiveness and metastatic potential. The highly invasive MDA-MB-231 cell line was treated with different concentrations of recombinant TGF-β1 and also with pharmacological inhibitors of p38 MAPK and ERK1/2. The migratory and invasive potential of these treated cells were examined in vitro by transwell assays. In general, TGF-β2, TβRI and TβRII are over-expressed in more aggressive cells, except for TβRI, which was also highly expressed in ZR-75-1 cells. In addition, TGF-β1-treated MDA-MB-231 cells presented significantly increased mRNA expression of MMP-2, MMP-9, MMP-14, TIMP-2 and RECK. TGF-β1 also increased TIMP-2, MMP-2 and MMP-9 protein levels but downregulated RECK expression. Furthermore, we analyzed the involvement of p38 MAPK and ERK1/2, representing two well established Smad-independent pathways, in the proposed mechanism. Inhibition of p38MAPK blocked TGF-β1-increased mRNA expression of all MMPs and MMP inhibitors analyzed, and prevented TGF-β1 upregulation of TIMP-2 and MMP-2 proteins. Moreover, ERK1/2 inhibition increased RECK and prevented the TGF-β1 induction of pro-MMP-9 and TIMP-2 proteins. TGF-β1-enhanced migration and invasion capacities were blocked by p

The Gene Polymorphism of the Angiotensin I-Converting Enzyme Correlates with Tumor Size and Patient Survival in Colorectal Cancer Patients

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Christoph Röcken

2007-09-01

Full Text Available We studied the putative significance of angiotensin I-converting enzyme (ACE in colorectal cancer (CRC biology. Local expression of ACE was investigated by quantitative reverse transcription- polymerase chain reaction and by immunohistochemistry in CRCs and adenomas. ACE insertion (I/deletion (D polymorphism was studied in 141 CRC patients and 189 controls. ACE mRNA was upregulated in CRCs compared to corresponding nonlesional tissues (2.5-fold; P = .009. ACE protein was more commonly expressed in adenomas [17 (81 %] and cancer epithelial cells [22 (100%] than in corresponding non-neoplastic crypt and surface epithelium [2 (10% and 2 (9%, respectively]. Thirty-seven CRC patients (26% carried II genotype, 69 (49% carried ID genotype, 35 (25% carried DD genotype. The distribution of the genotypes did not differ from that of controls. Female CRC patients more commonly carried the ID genotype and less frequently the II and DD genotypes compared with male patients (P = .033. Men heterozygous or homozygous for the D-allele had larger tumors compared to carriers of the II genotype (P < .01. Women homozygous for the D-allele lived longer than carriers of the ID and II genotypes. Our study shows that ACE is differentially expressed in CRCs and that gene polymorphism is associated with gender-specific differences in primary tumor size and patient survival.

Differential Analysis of the Nasal Microbiome of Pig Carriers or Non-Carriers of Staphylococcus aureus

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Espinosa-Gongora, Carmen; Larsen, Niels; Schonning, Kristian

2016-01-01

pathogen in animal carriers. The aim of this study was to determine whether the nasal microbiome of pig S. aureus carriers differs from that of non-carriers. The V3-V5 region of the 16S rRNA gene was sequenced from nasal swabs of 44 S. aureus carriers and 56 non-carriers using the 454 GS FLX titanium...... microbiome of pigs that are not colonized with S. aureus harbours several species/taxa that are significantly less abundant in pig carriers, suggesting that the nasal microbiota may play a role in the individual predisposition to S. aureus nasal carriage in pigs. Further research is warranted to isolate...

Personality traits in Huntington's disease: An exploratory study of gene expansion carriers and non-carriers.

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Larsen, Ida Unmack; Mortensen, Erik Lykke; Vinther-Jensen, Tua; Nielsen, Jørgen Erik; Knudsen, Gitte Moos; Vogel, Asmus

2016-12-01

Huntington's disease (HD) is associated with risk for developing psychiatric symptoms. Vulnerability or resilience to psychiatric symptoms may be associated with personality traits. This exploratory study, aimed to investigate personality traits in a large cohort of HD carriers and at risk gene-expansion negative individuals (HD non-carriers), exploring whether carrying the HD gene or growing up in an HD family influences personality traits. Forty-seven HD carriers, Thirty-nine HD non-carriers, and 121 healthy controls answered the Danish version of the revised NEO personality inventory. Comparisons between HD carriers and HD non-carriers were mostly non-significant but the combined group of HD carriers and non-carriers showed significantly higher scores on the facets: "hostility," "assertiveness," and "activity" and on the trait "Conscientiousness" relative to controls, "Conscientiousness" have been associated with resilience to psychiatric symptoms. Twelve HD carriers and non-carriers were classified as depressed and showed significantly lower scores on "Extraversion" and "Conscientiousness" and significantly higher scores on "Neuroticism," which are associated with vulnerability to psychiatric symptoms. Our findings suggest that, there is no direct effect of the HD gene on personality traits, but that personality assessment may be relevant to use when identifying individuals from HD families who are vulnerable to develop psychiatric symptoms. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Peptide-Carrier Conjugation

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Hansen, Paul Robert

2015-01-01

To produce antibodies against synthetic peptides it is necessary to couple them to a protein carrier. This chapter provides a nonspecialist overview of peptide-carrier conjugation. Furthermore, a protocol for coupling cysteine-containing peptides to bovine serum albumin is outlined....

Association between polymorphisms in the TSHR gene and Graves' orbitopathy.

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Beata Jurecka-Lubieniecka

Full Text Available BACKGROUND: Graves' orbitopathy (GO as well as Graves' disease (GD hyperthyroidism originate from an autoimmune reaction against the common auto-antigen, thyroid-stimulating hormone receptor (TSHR. GO phenotype is associated with environmental risk factors, mainly nicotinism, as well as genetic risk factors which initiate an immunologic reaction. In some patients GO is observed before diagnosis of GD hyperthyroidism, while it can also be observed far after diagnosis. The intensity of GO symptoms varies greatly in these patients. Thus, the pathogenesis of GD and GO may correlate with different genetic backgrounds, which has been confirmed by studies of correlations between GO and polymorphisms in cytokines involved in orbit inflammation. The aim of our analysis was to assess genetic predisposition to GO in young patients (age of diagnosis ≤30 years of age, for whom environmental effects had less time to influence outcomes than in adults. METHODS: 768 GD patients were included in the study. 359 of them had clinically evident orbitopathy (NOSPECS ≥2. Patients were stratified by age at diagnosis. Association analyses were performed for genes with a known influence on development of GD - TSHR, HLA-DRB1, cytotoxic T-lymphocyte antigen 4 (CTLA4 and lymphoid protein tyrosine phosphatase (PTPN22. RESULTS: The rs179247 TSHR polymorphism was associated with GO in young patients only. In young GO-free patients, allele A was statistically more frequent and homozygous carriers had a considerable lower risk of disease incidence than patients with AG or GG genotypes. Those differences were not found in either elderly patients or the group analyzed as a whole. CONCLUSIONS: Allele A of the rs179247 polymorphism in the TSHR gene is associated with lower risk of GO in young GD patients.

A paradoxical association of an oxytocin receptor gene polymorphism: Early-life adversity and vulnerability to depression

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Robyn Jane McQuaid

2013-07-01

Full Text Available Several prosocial behaviors may be influenced by the hormone oxytocin. In line with this perspective, the oxytocin receptor (OXTR gene single nucleotide polymorphism (SNP, rs53576, has been associated with a broad range of social behaviors. In this regard, the G allele of the OXTR SNP has been accompanied by beneficial attributes such as increased empathy, optimism and trust. In the current study among university students (N = 288, it was shown that early-life maltreatment was associated with depressive symptoms, and that the OXTR genotype moderated this relationship, such that under high levels of childhood maltreatment, only individuals with GG/GA genotype demonstrated increased depressive symptomatology compared to those with the AA genotype. In addition, the role of distrust in mediating the relation between childhood maltreatment and depression seemed to be more important among G allele carriers compared to individuals with the AA genotype. Thus, a breach in trust (i.e. in the case of early-life abuse or neglect may have a more deleterious effect among G carriers, who have been characterized as more prosocial and attuned to social cues. The data suggested that G carriers of the OXTR might favor social sensitivity and thus might have been more vulnerable to the effects of early-life adversity.

Association of the C-Reactive Protein Gene (CRP rs1205 C>T Polymorphism with Aortic Valve Calcification in Patients with Aortic Stenosis

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Ewa Wypasek

2015-10-01

Full Text Available Elevation in C-reactive protein (CRP levels have been shown in patients with aortic valve stenosis (AS. Minor allele of the CRP gene (CRP rs1205 C>T polymorphism has been associated with lower plasma CRP concentrations in cohorts of healthy and atherosclerotic patients. Considering the existing similarities between atherosclerosis and AS, we examined the effect of CRP rs1205 C>T polymorphism on the AS severity. Three hundred consecutive Caucasian patients diagnosed with AS were genotyped for the rs1205 C>T polymorphism using the TaqMan assay. Severity of the AS was assessed using transthoracic echocardiography. The degree of calcification was analyzed semi-quantitatively. Carriers of the rs1205 T allele were characterized by elevated serum CRP levels (2.53 (1.51–3.96 vs. 1.68 (0.98–2.90 mg/L, p < 0.001 and a higher proportion of the severe aortic valve calcification (70.4% vs. 55.1%, p = 0.01 compared with major homozygotes. The effect of CRP rs1205 polymorphism on CRP levels is opposite in AS-affected than in unaffected subjects, suggesting existence of a disease-specific molecular regulatory mechanism. Furthermore, rs1205 variant allele predisposes to larger aortic valve calcification, potentially being a novel genetic risk marker of disease progression.

Plasminogen activator inhibitor-1 4G/5G gene polymorphism and coronary artery disease in the Chinese Han population: a meta-analysis.

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Li, Yan-yan

2012-01-01

The polymorphism of plasminogen activator inhibitor-1 (PAI-1) 4G/5G gene has been indicated to be correlated with coronary artery disease (CAD) susceptibility, but study results are still debatable. The present meta-analysis was performed to investigate the association between PAI-1 4G/5G gene polymorphism and CAD in the Chinese Han population. A total of 879 CAD patients and 628 controls from eight separate studies were involved. The pooled odds ratio (OR) for the distribution of the 4G allele frequency of PAI-1 4G/5G gene and its corresponding 95% confidence interval (CI) was assessed by the random effect model. The distribution of the 4 G allele frequency was 0.61 for the CAD group and 0.51 for the control group. The association between PAI-1 4G/5G gene polymorphism and CAD in the Chinese Han population was significant under an allelic genetic model (OR = 1.70, 95% CI = 1.18 to 2.44, P = 0.004). The heterogeneity test was also significant (P5G gene polymorphism was implied to be associated with increased CAD risk. Carriers of the 4G allele of the PAI-1 4G/5G gene might predispose to CAD.

Genetic polymorphisms of hemostatic factors and thrombotic risk in non BCR-ABL myeloproliferative neoplasms: A pilot study

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Dambrauskienė R

2017-06-01

Full Text Available The most important complications of Philadelphianegagive (non BCR-ABL myeloproliferative neoplasms (MPNs are vascular events. Our aim was to evaluate the effects of single nucleotide polymorphisms (SNPs, platelet glycoproteins (GPs (Ia/IIa, Ibα, IIb/IIIa and VI, von Willebrand factor (vWF, coagulation factor VII (FVII, β-fibrinogen, and the risk of thrombosis in patients with non BCR-ABL MPNs at the Lithuanian University of Health Sciences. Kaunas, Lithuania. Genotyping was done for 108 patients. The TT genotype of the GP Ia/IIa c.807C>T polymorphism was more frequently found in the group of MPN patients with arterial thrombosis compared to MPN patients who were thrombosis-free [26.5 vs. 11.5%, p = 0.049; odds ratio (OR 2.68; 95% confidence interval (95% CI 1.01-7.38]. The CT genotype of the β-fibrinogen c.-148C>T polymorphism occurred more frequently in MPN patients with arterial, and total thrombosis compared to the wild or homozygous genotype (57.7 vs. 40.0 vs. 12.5%; p = 0.027, (64.7 vs. 44.4 vs. 25%; p = 0.032, respectively. The carrier state for the c.-323P10 variant of FVII SNP (summation of P10/10 and P0/10 was more frequent in MPN patients with thrombosis compared to the wild-type genotype carriers (71.4 vs. 43.4%; p = 0.049; OR 3.26; 95% CI 1.01-11.31. The coexistence of heterozygous β-fibrinogen c.-148C>T and FVII c.-323P0/10 SNP, increased the risk of arterial thrombosis (21.1 vs. 3.7%, p = 0.008; OR 6.93; 95% CI 1.38-34.80. The TT genotype of GP Ia/IIa c.807C>T, the CT genotype of β-fibrinogen c.-148C>T and FVII c.-323P0/10 SNP could be associated with risk of thrombosis in MPN patients.

Brain function in carriers of a genome-wide supported bipolar disorder variant.

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Erk, Susanne; Meyer-Lindenberg, Andreas; Schnell, Knut; Opitz von Boberfeld, Carola; Esslinger, Christine; Kirsch, Peter; Grimm, Oliver; Arnold, Claudia; Haddad, Leila; Witt, Stephanie H; Cichon, Sven; Nöthen, Markus M; Rietschel, Marcella; Walter, Henrik

2010-08-01

The neural abnormalities underlying genetic risk for bipolar disorder, a severe, common, and highly heritable psychiatric condition, are largely unknown. An opportunity to define these mechanisms is provided by the recent discovery, through genome-wide association, of a single-nucleotide polymorphism (rs1006737) strongly associated with bipolar disorder within the CACNA1C gene, encoding the alpha subunit of the L-type voltage-dependent calcium channel Ca(v)1.2. To determine whether the genetic risk associated with rs1006737 is mediated through hippocampal function. Functional magnetic resonance imaging study. University hospital. A total of 110 healthy volunteers of both sexes and of German descent in the Hardy-Weinberg equilibrium for rs1006737. Blood oxygen level-dependent signal during an episodic memory task and behavioral and psychopathological measures. Using an intermediate phenotype approach, we show that healthy carriers of the CACNA1C risk variant exhibit a pronounced reduction of bilateral hippocampal activation during episodic memory recall and diminished functional coupling between left and right hippocampal regions. Furthermore, risk allele carriers exhibit activation deficits of the subgenual anterior cingulate cortex, a region repeatedly associated with affective disorders and the mediation of adaptive stress-related responses. The relevance of these findings for affective disorders is supported by significantly higher psychopathology scores for depression, anxiety, obsessive-compulsive thoughts, interpersonal sensitivity, and neuroticism in risk allele carriers, correlating negatively with the observed regional brain activation. Our data demonstrate that rs1006737 or genetic variants in linkage disequilibrium with it are functional in the human brain and provide a neurogenetic risk mechanism for bipolar disorder backed by genome-wide evidence.

Association of renin-angiotensin system genes polymorphism with progression of diabetic nephropathy in patients with type 1 diabetes mellitus

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Ilić Vesna

2014-01-01

Full Text Available Background/Aim. Diabetic nephropathy (DN as a major microvascular complication of diabetes mellitus (DM include a progressive increase in urinary albumin excretion in association with an increase in blood pressure and to end stage renal failure. Hypertension connected with renin-angiotensin system (RAS hyperactivity and corresponding genotypes, angiotensinogen (AGT, angiotensine-converting enzyme (ACE and angiotensin II type 1 receptor (AT1R, predispose the increasing risk of DN. The aim of this study was to assess the distribution of AGT, ACE and AT1R gene polymorphisms in patients with type 1 DM according to the level of DN and patients clinical characteristics. Methods. The study included 79 type 1 diabetic patients. Inclusion criteria were: age between 20-40, duration of diabetes > 5 years, and no other severe diseases. Clinical characteristics were gained from interviewing the patients. Polymorphism was detected by polymerase chain reaction (PCR and restriction fragment length polymorphism using restriction enzymes Psy I (Tth 111 I and Hae III. Results. The patients with proteinuria compared with normo- and microalbuminuric patients, highly differed in age, diabetes duration, blood pressure level, hypertension, rethynopathy and urinary albumin excretion values (p < 0.001. No statistically significant difference between the groups was found for the ACE and AT1R gene polymorphisms distribution. The presence of TT genotype of the M235T polymorphism was significantly higher in the group with proteinuria (p < 0.05. The patients with hypertension raised nephropathy 5.2 times higher (OR = 5.20, p < 0.05 while carriers of TT allel developed nephropathy 28.38 times higher (OR = 28.389, p < 0.01 than those with MM genotype. Conclusion. Increased association of hypertension and TT angiotensinogen gene polymorphism in patients with diabetes mellitus with proteinuria could be a significant marker of diabetic nephropathy.

7 CFR 35.4 - Carrier.

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2010-01-01

... AND PLUMS Definitions § 35.4 Carrier. Carrier means any common or private carrier, including, but not being limited to, trucks, rail, airplanes, vessels, tramp or chartered steamers, whether carrying for...

Influence of the 5-HT3A Receptor Gene Polymorphism and Childhood Sexual Trauma on Central Serotonin Activity.

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Kuk-In Jang

Full Text Available Gene-environment interactions are important for understanding alterations in human brain function. The loudness dependence of auditory evoked potential (LDAEP is known to reflect central serotonergic activity. Single nucleotide polymorphisms (SNPs in the 5-HT3A serotonin receptor gene are associated with psychiatric disorders. This study aimed to investigate the effect between 5-HT3A receptor gene polymorphisms and childhood sexual trauma on the LDAEP as an electrophysiological marker in healthy subjects.A total of 206 healthy subjects were recruited and evaluated using the childhood trauma questionnaire (CTQ and hospital anxiety and depression scale (HADS. Peak-to-peak N1/P2 was measured at five stimulus intensities, and the LDAEP was calculated as the linear-regression slope. In addition, the rs1062613 SNPs of 5-HT3A (CC, CT, and TT were analyzed in healthy subjects.There was a significant interaction between scores on the CTQ-sexual abuse subscale and 5-HT3A genotype on the LDAEP. Subjects with the CC polymorphism had a significantly higher LDEAP than T carriers in the sexually abused group. In addition, CC genotype subjects in the sexually abused group showed a significantly higher LDAEP compared with CC genotype subjects in the non-sexually abused group.Our findings suggest that people with the CC polymorphism of the 5-HT3A gene have a greater risk of developing mental health problems if they have experienced childhood sexual abuse, possibly due to low central serotonin activity. Conversely, the T polymorphism may be protective against any central serotonergic changes following childhood sexual trauma.

Association of STin2 VNTR Polymorphism of Serotonin Transporter Gene with Lifelong Premature Ejaculation: A Case-Control Study in Han Chinese Subjects.

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Huang, Yuanyuan; Zhang, Xiansheng; Gao, Jingjing; Tang, Dongdong; Gao, Pan; Peng, Dangwei; Liang, Chaozhao

2016-10-07

BACKGROUND The STin2 VNTR polymorphism has a variable number of tandem repeats in intron 2 of the serotonin transporter gene. We aimed to explore the relationship between STin2 VNTR polymorphism and lifelong premature ejaculation (LPE). MATERIAL AND METHODS We recruited a total of 115 outpatients who complained of ejaculating prematurely and who were diagnosed as LPE, and 101 controls without PE complaint. Allelic variations of STin2 VNTR were genotyped using PCR-based technology. We evaluated the associations between STin2 VNTR allelic and genotypic frequencies and LPE, as well as the intravaginal ejaculation latency time (IELT) of different STin2 VNTR genotypes among LPE patients. RESULTS The patients and controls did not differ significantly in terms of any characteristic except age. A significantly higher frequency of STin2.12/12 genotype was found among LPE patients versus controls (P=0.026). Frequency of patients carrying at least 1 copy of the 10-repeat allele was significantly lower compared to the control group (28.3% vs. 41.8%, OR=0.55; 95%CI=0.31-0.97, P=0.040). In the LPE group, the mean IELT showed significant difference in STin2.12/12 genotype when compared to those with STin2.12/10 and STin2.10/10 genotypes. The mean IELT in10-repeat allele carriers was 50% longer compared to homozygous carriers of the STin2.12 allele. CONCLUSIONS Our results indicate the presence of STin2.10 allele is a protective factor for LPE. Men carrying the higher expression genotype STin2. 12/12 have shorter IELT than 10-repeat allele carriers.

The c.-1639g>A polymorphism of the VKORC1 gene and his influence on the therapeutic response during oral anticoagulants use

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Kovač Mirjana

2009-01-01

Full Text Available Background/Aim. A single nucleotide polymorphism c.- 1639G>A in the promoter region of vitamin K-epoxide reductase (VKORC1 gene has been found to account for most of the variability in response to oral anticoagulants (OA. The aim of the study was to determine the incidence and the effect of c.-1639G>A polymorphism on the acenocoumarol dosage requirements in the group of patients under stable anticoagulation, and to estimate the variability in response to OA. Methods. Our study included 200 consecutive patients requiring low (n = 43, medium (n = 127 and high (n = 30 acenocoumarol dose. Results. Out of 43 low dose patients, 40 (93 % carried the A allele. The A allele was less frequent in the group of 30 patients requiring high dose: among these patients 13 (43.3% carried the A allele in the heterozygous form and none of them carried AA genotype. The patients with GG genotype required 2.6 times higher dose than the patients carriers of AA genotype (p < 0.0001. In 33 patients (16.5% the overdose occurred during the initiation of anticoagulant therapy and in 11 patients (5.5% it was associated with bleeding. Out of the group of 33 overdosed patients, 27 and 6 patients carried AA and GA genotype, respectively (p < 0.000001. Conclusion. VKORC1 significantly influenced OA dose and predicted individuals predisposed to unstable anticoagulation. The carriers of AA genotype required 2.6 time lower doses of OA than the carriares of GG genotype. Pharmacogenetic testing could predict a high risk of overdose among 28.5 % of our patients - carriers of AA genotype, before anticoagulation therapy initiation.

Frequency Of C3435 Mdr1 And A6896g Cyp3a5 Single Nucleotide Polymorphism in an Iranian Population and Comparison with Other Ethnic Groups

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N. AZARPIRA

2006-11-01

Full Text Available Background:It is well recognized that different patients respond in different ways to medications. The inter-individual variations are greater than the intera- individual variations,a finding consistent with the notion that inheritance is a determinant of drug responses. The recent identification of genetic polymorphisms in drug-metabolizing enzymes and drug transporters led to the hypothesis that genetic factors may be implicated in this interindividual variation. Single nucleotide polymorphism in common metabolic pathway,cytochrome P450 and common transporter,multidrug resistance-1 gene are two important sites that might involve clinically significant genetic variations. Ethnicity greatly influences these genetic polymorphism distributions. Methods: We studied the inheritance patterns of polymorphisms for MDR1 and CYP3A5 genes in the Iranian population and compared its genotype and allele frequencies with 3 different ethnic groups: Caucasian (United Kingdom, Chinese and Japanese. Results: We found striking differences in the distribution of MDR allelic variants between Iranian,Japanese and Chinese (p<0.02 and similar between the Iranian and Caucasian population.(p=0.06.Almost 50% of Iranian and Caucasian individuals were homozygous carriers of the variant T allele compared with 32% of the Japanese and 43% of the Chinese (p<0.02.More than half of Iranian subjects have at least one T allele,with lower P-gp level in small intestine.We also noted dramatic differences in the CYP3A5 alleles and genotypes distribution between Iranian subjects with other compared populations.99% of Iranian individuals were homozygous carriers of the variant G allele compared with about 70% of the Chinese and Japanese and 19% of the Caucasian population. The G/G genotype has a very low level of active cytochrome P450 enzyme.Conclusion:Our results emphasize the role of ethnicity in interindividual variability of the pharmacokinetic and pharmacodynamic characteristics

Ultrafast carrier dynamics in a p-type GaN wafer under different carrier distributions

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Fang, Yu; Yang, Junyi; Yang, Yong; Wu, Xingzhi; Xiao, Zhengguo; Zhou, Feng; Song, Yinglin

2016-02-01

The dependence of the carrier distribution on photoexcited carrier dynamics in a p-type Mg-doped GaN (GaN:Mg) wafer were systematically measured by femtosecond transient absorption (TA) spectroscopy. The homogeneity of the carrier distribution was modified by tuning the wavelength of the UV pulse excitation around the band gap of GaN:Mg. The TA kinetics appeared to be biexponential for all carrier distributions, and only the slower component decayed faster as the inhomogeneity of the carrier distribution increased. It was concluded that the faster component (50-70 ps) corresponded to the trap process of holes by the Mg acceptors, and the slower component (150-600 ps) corresponded to the combination of non-radiative surface recombination and intrinsic carrier recombination via dislocations. Moreover, the slower component increased gradually with the incident fluence due to the saturation of surface states.

The brain-derived neurotrophic factor (BDNF val66met polymorphism differentially affects performance on subscales of the Wechsler memory scale – third edition (WMS-III

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Yvette Nicole Lamb

2015-08-01

Full Text Available Single nucleotide polymorphisms in the brain-derived neurotrophic factor (BDNF gene and the catechol-O-methyltransferase (COMT gene influence brain structure and function, as well as cognitive abilities. They are most influential in the hippocampus and prefrontal cortex (PFC, respectively. Recall and recognition are forms of memory proposed to have different neural substrates, with recall having a greater dependence on the PFC and hippocampus. This study aimed to determine whether the BDNF val66met or COMT val158met polymorphisms differentially affect recall and recognition, and whether these polymorphisms interact. A sample of 100 healthy adults was assessed on recall and familiarity-based recognition using the Faces and Family Pictures subscales of the Wechsler Memory Scale – Third Edition (WMS-III. COMT genotype did not affect performance on either task. The BDNF polymorphism (i.e. met carriers relative to val homozygotes was associated with poorer recall ability, while not influencing recognition. Combining subscale scores in memory tests such as the WMS might obscure gene effects. Our results demonstrate the importance of distinguishing between recall and familiarity-based recognition in neurogenetics research.

Hot carrier degradation in semiconductor devices

CERN Document Server

2015-01-01

This book provides readers with a variety of tools to address the challenges posed by hot carrier degradation, one of today’s most complicated reliability issues in semiconductor devices.  Coverage includes an explanation of carrier transport within devices and book-keeping of how they acquire energy (“become hot”), interaction of an ensemble of colder and hotter carriers with defect precursors, which eventually leads to the creation of a defect, and a description of how these defects interact with the device, degrading its performance. • Describes the intricacies of hot carrier degradation in modern semiconductor technologies; • Covers the entire hot carrier degradation phenomenon, including topics such as characterization, carrier transport, carrier-defect interaction, technological impact, circuit impact, etc.; • Enables detailed understanding of carrier transport, interaction of the carrier ensemble with the defect precursors, and an accurate assessment of how the newly created defects imp...

Maintainable substrate carrier for electroplating

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Chen, Chen-An [Milpitas, CA; Abas, Emmanuel Chua [Laguna, PH; Divino, Edmundo Anida [Cavite, PH; Ermita, Jake Randal G [Laguna, PH; Capulong, Jose Francisco S [Laguna, PH; Castillo, Arnold Villamor [Batangas, PH; Ma,; Xiaobing, Diana [Saratoga, CA

2012-07-17

One embodiment relates to a substrate carrier for use in electroplating a plurality of substrates. The carrier includes a non-conductive carrier body on which the substrates are placed and conductive lines embedded within the carrier body. A plurality of conductive clip attachment parts are attached in a permanent manner to the conductive lines embedded within the carrier body. A plurality of contact clips are attached in a removable manner to the clip attachment parts. The contact clips hold the substrates in place and conductively connecting the substrates with the conductive lines. Other embodiments, aspects and features are also disclosed.

Free-Ranging Synanthropic Birds (Ardea alba and Columba livia domestica) as Carriers of Salmonella spp. and Diarrheagenic Escherichia coli in the Vicinity of an Urban Zoo.

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de Oliveira, Mirela C V; Camargo, Beatriz Q; Cunha, Marcos P V; Saidenberg, Andre Becker; Teixeira, Rodrigo H F; Matajira, Carlos E C; Moreno, Luisa Z; Gomes, Vasco T M; Christ, Ana P G; Barbosa, Mikaela R F; Sato, Maria I Z; Moreno, Andrea M; Knöbl, Terezinha

2018-01-01

The presence of free-ranging urban birds is a risk factor for transmitting pathogens to captive animals and humans alike, including Salmonella spp. and diarrheagenic Escherichia coli. Cloacal swabs from 156 synanthropic Great egrets (Ardea alba) and feral pigeons (Columba livia domestica) that inhabit the surroundings of an urban zoo were processed for the identification of Salmonella spp. and diarrheagenic E. coli pathotypes. Bacterial species identification and genotypic characterization employed the matrix-assisted laser desorption ionization-time of flight mass spectrometry and PCR techniques, respectively, comparing their phylogenetic profiles through amplified fragment length polymorphism (AFLP) analysis. A total of 11 birds were positive for Salmonella Typhimurium (7%) and 9 individuals (5.8%) for diarrheagenic E. coli (enteropathogenic E. coli/Shiga-toxin producing E. coli [EPEC/STEC]) strains. S. Typhimurium strains presented highly similar AFLP profiles (85-100%), whereas EPEC/STEC strains showed more polymorphism. The results show free-ranging birds as carriers for both microorganisms in a zoo environment in Brazil for the first time and suggest these species as possible sources of infection to other animals as well as exposing personnel and visitors to potential zoonotic microorganisms. The presence of carriers highlights the importance of a surveillance system and the need for preventive measures to avoid attracting growing number of synanthropic avian species.

The C242T polymorphism of the p22-phox gene (CYBA is associated with higher left ventricular mass in Brazilian hypertensive patients

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Krieger José E

2011-08-01

Full Text Available Abstract Background Reactive oxygen species have been implicated in the physiopathogenesis of hypertensive end-organ damage. This study investigated the impact of the C242T polymorphism of the p22-phox gene (CYBA on left ventricular structure in Brazilian hypertensive subjects. Methods We cross-sectionally evaluated 561 patients from 2 independent centers [Campinas (n = 441 and Vitória (n = 120] by clinical history, physical examination, anthropometry, analysis of metabolic and echocardiography parameters as well as p22-phox C242T polymorphism genotyping. In addition, NADPH-oxidase activity was quantified in peripheral mononuclear cells from a subgroup of Campinas sample. Results Genotype frequencies in both samples were consistent with the Hardy- Weinberg equilibrium. Subjects with the T allele presented higher left ventricular mass/height2.7 than those carrying the CC genotype in Campinas (76.8 ± 1.6 vs 70.9 ± 1.4 g/m2.7; p = 0.009, and in Vitória (45.6 ± 1.9 vs 39.9 ± 1.4 g/m2.7; p = 0.023 samples. These results were confirmed by stepwise regression analyses adjusted for age, gender, blood pressure, metabolic variables and use of anti-hypertensive medications. In addition, increased NADPH-oxidase activity was detected in peripheral mononuclear cells from T allele carriers compared with CC genotype carriers (p = 0.03. Conclusions The T allele of the p22-phox C242T polymorphism is associated with higher left ventricular mass/height2.7 and increased NADPH-oxidase activity in Brazilian hypertensive patients. These data suggest that genetic variation within NADPH-oxidase components may modulate left ventricular remodeling in subjects with systemic hypertension.

Non-permeable substrate carrier for electroplating

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Abas, Emmanuel Chua; Chen, Chen-An; Ma, Diana Xiaobing; Ganti, Kalyana Bhargava

2012-11-27

One embodiment relates to a substrate carrier for use in electroplating a plurality of substrates. The substrate carrier comprises a non-conductive carrier body on which the substrates are to be held. Electrically-conductive lines are embedded within the carrier body, and a plurality of contact clips are coupled to the electrically-conductive lines embedded within the carrier body. The contact clips hold the substrates in place and electrically couple the substrates to the electrically-conductive lines. The non-conductive carrier body is continuous so as to be impermeable to flow of electroplating solution through the non-conductive carrier body. Other embodiments, aspects and features are also disclosed.

DNA glycosylases involved in base excision repair may be associated with cancer risk in BRCA1 and BRCA2 mutation carriers.

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Ana Osorio

2014-04-01

Full Text Available Single Nucleotide Polymorphisms (SNPs in genes involved in the DNA Base Excision Repair (BER pathway could be associated with cancer risk in carriers of mutations in the high-penetrance susceptibility genes BRCA1 and BRCA2, given the relation of synthetic lethality that exists between one of the components of the BER pathway, PARP1 (poly ADP ribose polymerase, and both BRCA1 and BRCA2. In the present study, we have performed a comprehensive analysis of 18 genes involved in BER using a tagging SNP approach in a large series of BRCA1 and BRCA2 mutation carriers. 144 SNPs were analyzed in a two stage study involving 23,463 carriers from the CIMBA consortium (the Consortium of Investigators of Modifiers of BRCA1 and BRCA2. Eleven SNPs showed evidence of association with breast and/or ovarian cancer at p<0.05 in the combined analysis. Four of the five genes for which strongest evidence of association was observed were DNA glycosylases. The strongest evidence was for rs1466785 in the NEIL2 (endonuclease VIII-like 2 gene (HR: 1.09, 95% CI (1.03-1.16, p = 2.7 × 10(-3 for association with breast cancer risk in BRCA2 mutation carriers, and rs2304277 in the OGG1 (8-guanine DNA glycosylase gene, with ovarian cancer risk in BRCA1 mutation carriers (HR: 1.12 95%CI: 1.03-1.21, p = 4.8 × 10(-3. DNA glycosylases involved in the first steps of the BER pathway may be associated with cancer risk in BRCA1/2 mutation carriers and should be more comprehensively studied.

Association of BDNF Val66Met polymorphism with HPA and SAM axis reactivity to psychological and physical stress.

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Tsuru, Jusen; Tanaka, Yoshihiro; Ishitobi, Yoshinobu; Maruyama, Yoshihiro; Inoue, Ayako; Kawano, Aimi; Ikeda, Rie; Ando, Tomoko; Oshita, Harumi; Aizawa, Saeko; Masuda, Koji; Higuma, Haruka; Kanehisa, Masayuki; Ninomiya, Taiga; Akiyoshi, Jotaro

2014-01-01

Decreased expression of brain-derived neurotrophic factor (BDNF) is implicated in enhanced stress responses. The BDNF Val66Met polymorphism is associated with psychological changes; for example, carriers of the Met allele exhibit increased harm avoidance as well as a higher prevalence of depression and anxiety disorder. To analyze the effects of BDNF Val66Met on stress responses, we tested 226 university students (88 women and 138 men) using a social stress procedure (Trier Social Stress Test [TSST]) and an electrical stimulation stress test. Stress indices were derived from repeated measurements of salivary α-amylase, salivary cortisol, heart rate, and psychological testing during the stress tests. All subjects were genotyped for the Val66Met polymorphism (G196A). A significant three-way interaction (time [3 levels] × BDNF [Val/Val, Val/Met, Met/Met]; PBDNF had different effects on hypothalamic-pituitary-adrenocortical axis reactivity but not on sympathetic adrenomedullary reactivity in TSST and electrical stimulation tests.

ADRB3 Gene Trp64Arg Polymorphism and Essential Hypertension: A Meta-Analysis Including 9,555 Subjects.

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Li, Yan-Yan; Lu, Xin-Zheng; Wang, Hui; Zhou, Yan-Hong; Yang, Xin-Xing; Geng, Hong-Yu; Gong, Ge; Kim, Hyun Jun

2018-01-01

Background: Presence of the β 3-Adrenergic receptor (ADRB3) gene Trp64Arg (T64A) polymorphism may be associated with an increased susceptibility for essential hypertension (EH). A clear consensus, however, has yet to be reached. Objective and methods: To further elucidate the relationship between the ADRB3 gene Trp64Arg polymorphism and EH, a meta-analysis of 9,555 subjects aggregated from 16 individual studies was performed. The combined odds ratios (ORs) and their corresponding 95% confidence intervals (CI) were evaluated using either a random or fixed effect model. Results: We found a marginally significant association between ADRB3 gene Trp64Arg polymorphism and EH in the whole population under the additive genetic model (OR: 1.200, 95% CI: 1.00-1.43, P = 0.049). Association within the Chinese subgroup, however, was significant under allelic (OR: 1.150, 95% CI: 1.002-1.320, P = 0.046), dominant (OR: 1.213, 95% CI: 1.005-1.464, P = 0.044), heterozygous (OR: 1.430, 95% CI:1.040-1.970, P = 0.03), and additive genetic models (OR: 1.280, 95% CI: 1.030-1.580, P = 0.02). A significant association was also found in the Caucasian subgroup under allelic (OR: 1.850, 95% CI: 1. 260-2.720, P = 0.002), dominant (OR: 2.004, 95% CI: 1.316-3.052, P = 0.001), heterozygous (OR: 2.220, 95% CI: 1.450-3.400, P = 0.0002), and additive genetic models (OR: 2.000, 95% CI: 1. 330-3.010, P = 0.0009). Conclusions: The presence of the ADRB3 gene Trp64Arg polymorphism is positively associated with EH, especially in the Chinese and Caucasian population. The Arg allele carriers of ADRB3 gene Trp64Arg polymorphism may be at an increased risk for developing EH.

Positive association of the hepatic lipase gene polymorphism c.514C > T with estrogen replacement therapy response

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Pulchinelli Alvaro

2011-11-01

Full Text Available Abstract Background Hepatic lipase (HL, an enzyme present in the hepatic sinusoids, is responsible for the lipolysis of lipoproteins. Human HL contains four polymorphic sites: G-250A, T-710C, A-763G, and C-514T single-nucleotide polymorphism (SNPs. The last polymorphism is the focus of the current study. The genotypes associated with the C-514T polymorphism are CC (normal homozygous - W, CT (heterozygous - H, and TT (minor-allele homozygous - M. HL activity is significantly impaired in individuals of the TT and CT genotypes. A total of 58 post-menopausal women were studied. The subjects were hysterectomized women receiving hormone replacement therapy consisting of 0.625 mg of conjugated equine estrogen once a day. The inclusion criteria were menopause of up to three years and normal blood tests, radiographs, cervical-vaginal cytology, and densitometry. DNA was extracted from the buccal and blood cells of all 58 patients using a commercially available kit (GFX® - Amersham-Pharmacia, USA. Results Statistically significant reductions in triglycerides (t = 2.16; n = 58; p = 0.03 but not in total cholesterol (t = 0.14; n = 58; p = 0.89 were found after treatment. This group of good responders were carriers of the T allele; the CT and TT genotypes were present significantly more frequently than in the group of non-responders (p = 0.02 or p = 0.07, respectively. However, no significant difference in HDL-C (t = 0.94; n = 58; p = 0.35 or LDL-C (t = -0.83; n = 58; p = 0.41 was found in these patients. Conclusions The variation in lipid profile associated with the C-514T polymorphism is significant, and the T allele is associated with the best response to ERT.

Sex Differences in Risk for Alzheimer's Disease Related to Neurotrophin Gene Polymorphisms: The Cache County Memory Study.

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Matyi, Joshua; Tschanz, JoAnn T; Rattinger, Gail B; Sanders, Chelsea; Vernon, Elizabeth K; Corcoran, Chris; Kauwe, John S K; Buhusi, Mona

2017-11-09

Neurotrophins, including nerve-growth factor and brain-derived neurotrophic factor, have been implicated in Alzheimer's disease (AD). Associations between AD and neurotrophin signaling genes have been inconsistent, with few studies examining sex differences in risk. We examined four single-nucleotide polymorphisms (SNPs) involved in neurotrophin signaling (rs6265, rs56164415, rs2289656, rs2072446) and risk for AD by sex in a population-based sample of older adults. Three thousand four hundred and ninety-nine individuals without dementia at baseline [mean (standard deviation) age = 74.64 (6.84), 58% female] underwent dementia screening and assessment over four triennial waves. Cox regression was used to examine time to AD or right censoring for each SNP. Female carriers of the minor T allele for rs2072446 and rs56164415 had a 60% (hazard ratio [HR] = 1.60, 95% confidence interval [CI] = 1.02-2.51) and 93% (HR = 1.93, 95% CI = 1.30-2.84) higher hazard for AD, respectively, than male noncarriers of the T allele. Furthermore, male carriers of the T allele of rs2072446 had a 61% lower hazard (HR = 0.39, 95% CI = 0.14-1.06) than male noncarriers at trend-level significance (p = .07). The association between certain neurotrophin gene polymorphisms and AD differs by sex and may explain inconsistent findings in the literature. © The Author 2017. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Progranulin genetic polymorphisms influence progression of disability and relapse recovery in multiple sclerosis.

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Vercellino, Marco; Fenoglio, Chiara; Galimberti, Daniela; Mattioda, Alessandra; Chiavazza, Carlotta; Binello, Eleonora; Pinessi, Lorenzo; Giobbe, Dario; Scarpini, Elio; Cavalla, Paola

2016-07-01

Progranulin (GRN) is a multifunctional protein involved in inflammation and repair, and also a neurotrophic factor critical for neuronal survival. Progranulin is strongly expressed in multiple sclerosis (MS) brains by macrophages and microglia. In this study we evaluated GRN genetic variability in 400 MS patients, in correlation with clinical variables such as disease severity and relapse recovery. We also evaluated serum progranulin levels in the different groups of GRN variants carriers. We found that incomplete recovery after a relapse is correlated with an increased frequency of the rs9897526 A allele (odds ratio (OR) 4.367, p = 0.005). A more severe disease course (Multiple Sclerosis Severity Score > 5) is correlated with an increased frequency of the rs9897526 A allele (OR 1.886, p = 0.002) and of the rs5848 T allele (OR 1.580, p = 0.019). Carriers of the variants associated with a more severe disease course (rs9897526 A, rs5848 T) have significantly lower levels of circulating progranulin (80.5 ± 9.1 ng/mL vs. 165.7 ng/mL, p = 0.01). GRN genetic polymorphisms likely influence disease course and relapse recovery in MS. © The Author(s), 2015.

Does the Angiotensin-converting enzyme (ACE gene insertion/deletion polymorphism modify the response to ACE inhibitor therapy? – A systematic review

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Perna Annalisa

2005-10-01

Full Text Available Abstract Background Pharmacogenetic testing to individualize ACE inhibitor therapy remains controversial. We conducted a systematic review to assess the effect modification of the insertion/deletion (I/D polymorphism of the ACE gene on any outcome in patients treated with ACE inhibitors for cardiovascular and/or renal disease. Methods Our systematic review involved searching six electronic databases, then contacting the investigators (and pharmaceutical industry representatives responsible for the creation of these databases. Two reviewers independently selected relevant randomized, placebo-controlled trials and abstracted from each study details on characteristics and quality. Results Eleven studies met our inclusion criteria. Despite repeated efforts to contact authors, only four of the eleven studies provided sufficient data to quantify the effect modification by genotypes. We observed a trend towards better response to ACE inhibitors in Caucasian DD carriers compared to II carriers, in terms of blood pressure, proteinuria, glomerular filtration rate, ACE activity and progression to end-stage renal failure. Pooling of the results was inappropriate, due to heterogeneity in ethnicity, clinical domains and outcomes. Conclusion Lack of sufficient genetic data from the reviewed studies precluded drawing any convincing conclusions. Better reporting of genetic data are needed to confirm our preliminary observations concerning better response to ACE inhibitors among Caucasian DD carriers as compared to II carriers.

BDNF val66met Polymorphism Impairs Hippocampal Long-Term Depression by Down-Regulation of 5-HT3 Receptors

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Rui Hao

2017-10-01

Full Text Available Brain-derived neurotrophic factor (BDNF is a key regulator of neuronal plasticity and cognitive functions. BDNF val66met polymorphism, a human single-nucleotide polymorphism (SNP in the pro-domain of BDNF gene, is associated with deficits in activity-dependent BDNF secretion and hippocampus-dependent memory. However, the underlying mechanism remains unclear. Here we show that in the BDNFMet/Met mouse line mimicking the human SNP, BDNF expression in the hippocampus was decreased. There was a reduction in the total number of cells in hippocampal CA1 region, while hippocampal expression of mRNAs for NR2a, 2b, GluR1, 2 and GABAARβ3 subunits were up-regulated. Although basal glutamatergic neurotransmission was unaltered, hippocampal long-term depression (LTD induced by low-frequency stimulation was impaired, which was partially rescued by exogenous application of BDNF. Interestingly, 5-HT3a receptors were down-regulated in the hippocampus of BDNFMet/Met mice, whereas 5-HT2c receptors were up-regulated. Moreover, impaired LTD in BDNFMet/Met mice was reversed by 5-HT3aR agonist. Thus, these observations indicate that BDNF val66met polymorphism changes hippocampal synaptic plasticity via down-regulation of 5-HT3a receptors, which may underlie cognition dysfunction of Met allele carriers.

The association of factor V G1961A (factor V Leiden), prothrombin G20210A, MTHFR C677T and PAI-1 4G/5G polymorphisms with recurrent pregnancy loss in Bosnian women.

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Jusić, Amela; Balić, Devleta; Avdić, Aldijana; Pođanin, Maja; Balić, Adem

2018-08-01

Aim To investigate association of factor V Leiden, prothrombin G20210A, MTHFR C677T and PAI-1 4G/5G polymorphisms with recurrent pregnancy loss in Bosnian women. Methods A total of 60 women with two or more consecutive miscarriages before 20 weeks of gestation with the same partners and without history of known causes or recurrent pregnancy loss were included. A control group included 80 healthy women who had one or more successful pregnancies without history of any complication which could be associated with miscarriages. Genotyping of factor V Leiden, prothrombin G20210A, MTHFR C677T and PAI-1 4G/5G polymorphisms were performed by polymerase chain reaction/restriction fragments length polymorphism method (PCR/RFLP). Results Both factor V Leiden and MTHFR C677T polymorphisms were significantly associated with recurrent pregnancy loss (RPL) in Bosnian women while prothrombin G20210A and PAI-1 4G/5G polymorphisms did not show strongly significant association. Conclusion The presence of thrombophilic polymorphisms may predispose women to recurrent pregnancy loss. Future investigation should be addressed in order to find when carriers of those mutations, polymorphisms should be treated with anticoagulant therapy. Copyright© by the Medical Assotiation of Zenica-Doboj Canton.

Klotho G-395A gene polymorphism: impact on progression of end-stage renal disease and development of cardiovascular complications in children on dialysis.

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Elghoroury, Eman A; Fadel, Fatina I; Elshamaa, Manal F; Kandil, Dina; Salah, Doaa M; El-Sonbaty, Marwa M; Farouk, Hebatallah; Raafat, Mona; Nasr, Soha

2018-06-01

Klotho G-395-A gene polymorphism may impact children with end-stage renal disease (ESRD). We investigated the relevance of Klotho G-395-A on ESRD development and progression, and its relationship with evolution of cardiovascular complications in pediatric dialysis patients. Fifty-five children with chronic kidney disease (CKD) and seventy healthy children were genotyped for Klotho G-395A. Incidence of GA/AA genotypes and A allele were higher in ESRD patients compared with controls (54.5 vs. 7.1%, P < 0.001; 30.9 vs. 13.6%, P = 0.001, respectively). Also, children with GA/AA genotypes were 15.6 times more likely to develop ESRD than with GG genotype (95% CI 5.4-44.7, P < 0.001). A allele carriers have 2.8 times higher risk of developing ESRD than those with G allele (95% CI 1.5-5.35, P = 0.001). Also, the A allele could be considered a predictor of cardiovascular disease (CVD), as carriers have 161 times higher risk of cardiovascular complications than non-carriers (95% CI 21-1233, P < 0.001). All ESRD patients with CVD presented with left ventricular hypertrophy (LVH) and the frequency of A allele was significantly higher among ESRD children with LVH, whereas G allele frequency was significantly higher among ESRD children without LVH. The A allele of the G-395A Klotho gene polymorphism shows a significantly higher frequency among children with CKD and those with CVD and LVH. This mutant allele could be used as a risk marker for the development of ESRD as well as a predictor of CVD in these children.

Assessing associations between the AURKA-HMMR-TPX2-TUBG1 functional module and breast cancer risk in BRCA1/2 mutation carriers.

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Ignacio Blanco

Full Text Available While interplay between BRCA1 and AURKA-RHAMM-TPX2-TUBG1 regulates mammary epithelial polarization, common genetic variation in HMMR (gene product RHAMM may be associated with risk of breast cancer in BRCA1 mutation carriers. Following on these observations, we further assessed the link between the AURKA-HMMR-TPX2-TUBG1 functional module and risk of breast cancer in BRCA1 or BRCA2 mutation carriers. Forty-one single nucleotide polymorphisms (SNPs were genotyped in 15,252 BRCA1 and 8,211 BRCA2 mutation carriers and subsequently analyzed using a retrospective likelihood approach. The association of HMMR rs299290 with breast cancer risk in BRCA1 mutation carriers was confirmed: per-allele hazard ratio (HR = 1.10, 95% confidence interval (CI 1.04-1.15, p = 1.9 x 10(-4 (false discovery rate (FDR-adjusted p = 0.043. Variation in CSTF1, located next to AURKA, was also found to be associated with breast cancer risk in BRCA2 mutation carriers: rs2426618 per-allele HR = 1.10, 95% CI 1.03-1.16, p = 0.005 (FDR-adjusted p = 0.045. Assessment of pairwise interactions provided suggestions (FDR-adjusted pinteraction values > 0.05 for deviations from the multiplicative model for rs299290 and CSTF1 rs6064391, and rs299290 and TUBG1 rs11649877 in both BRCA1 and BRCA2 mutation carriers. Following these suggestions, the expression of HMMR and AURKA or TUBG1 in sporadic breast tumors was found to potentially interact, influencing patients' survival. Together, the results of this study support the hypothesis of a causative link between altered function of AURKA-HMMR-TPX2-TUBG1 and breast carcinogenesis in BRCA1/2 mutation carriers.

Gender-dependent association of HSD11B1 single nucleotide polymorphisms with glucose and HDL-C levels

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Luciane Viater Turek

2014-09-01

Full Text Available In this study, we investigated the influence of two SNPs (rs846910 and rs12086634 of the HSD11B1 gene that encodes 11β-hydroxysteroid dehydrogenase type 1(11β-HSD1, the enzyme that catalyzes the conversion of cortisol to cortisone, on variables associated with obesity and metabolic syndrome in 215 individuals of both sexes from southern Brazil. The HSD11B1 gene variants were genotyped using the TaqMan SNP genotyping assay. Glucose, triglycerides, total cholesterol, HDL-cholesterol and LDL-cholesterol were measured by standard automated methods. Significant results were found in women, with carriers of the G allele of SNP rs12086634 having higher glucose levels than non-carriers. Carriers of the A allele of SNP rs846910 had higher levels of HDL-cholesterol. The involvement of both polymorphisms as independent factors in determining the levels of glucose and HDL-cholesterol was confirmed by multiple regression analysis (β = 0.19 ± 0.09, p = 0.03 and β = 0.22 ± 0.10, p = 0.03, respectively. Our findings suggest that the HSD11B1SNPs studied may indirectly influence glucose and HDL-cholesterol metabolism in women, possibly through down-regulation of the HSD11B1 gene by estrogen.

Toll-like receptor 2 -196 to -174 del polymorphism influences the susceptibility of Han Chinese people to Alzheimer's disease

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Mao Cai-Xia

2011-10-01

Full Text Available Abstract Background Toll-like receptor 2 (TLR2 represents a reasonable functional and positional candidate gene for Alzheimer's disease (AD as it is located under the linkage region of AD on chromosome 4q, and functionally is involved in the microglia-mediated inflammatory response and amyloid-β clearance. The -196 to -174 del polymorphism affects the TLR2 gene and alters its promoter activity. Methods We recruited 800 unrelated Northern Han Chinese individuals comprising 400 late-onset AD (LOAD patients and 400 healthy controls matched for gender and age. The -196 to -174 del polymorphism in the TLR2 gene was genotyped using the polymerase chain reaction (PCR method. Results There were significant differences in genotype (P = 0.026 and allele (P = 0.009 frequencies of the -196 to -174 del polymorphism between LOAD patients and controls. The del allele was associated with an increased risk of LOAD (OR = 1.31, 95% CI = 1.07-1.60, Power = 84.9%. When these data were stratified by apolipoprotein E (ApoE ε4 status, the observed association was confined to ApoE ε4 non-carriers. Logistic regression analysis suggested an association of LOAD with the polymorphism in a recessive model (OR = 1.64, 95% CI = 1.13-2.39, Bonferroni corrected P = 0.03. Conclusions Our data suggest that the -196 to -174 del/del genotype of TLR2 may increase risk of LOAD in a Northern Han Chinese population.

Association between −308 G/A TNF-α Polymorphism and Appendicular Skeletal Muscle Mass Index as a Marker of Sarcopenia in Normal Weight Obese Syndrome

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L. Di Renzo

2013-01-01

Full Text Available Background and Aim. Normal weight obese (NWO syndrome is characterized by normal body mass index (BMI, but high amount of fat mass and reduced lean mass. We evaluated allelic frequency of the G/A −308 TNF-α polymorphism and prevalence of sarcopenia in NWO. Methods. We enrolled 120 Italian healthy women, distinguished into 3 groups: normal weight (NW; NWO, and preobese-obese (PreOB/OB and evaluated anthropometric parameters, body composition by dual X-ray absorptiometry, blood tests, and genotyping of G/A −308 TNF-α polymorphism. Results. We found a positive association between sarcopenic obesity and −308 TNF-α polymorphism. All obese women were sarcopenic and were no carrier of mutation (G/G. Among all G/G, NWO showed significant differences in lean mass and total body lean mass (TBLean with respect to NW and PreOB/OB (P<0.001. Regarding appendicular skeletal muscle mass index values, 4.21% of NW were sarcopenic (50% G/G and 50% G/A; the same percentage was observed in NWO subjects (100% G/G. Moreover, 2.10% of PreOB/OB were sarcopenic and all were G/G. Conclusion. Our study suggests that TNF-α polymorphism contributes to sarcopenic obesity susceptibility, in association with body composition. This is the first study that shows the importance of TNF-α polymorphism to determine TBLean variation in NWO syndrome.

Tailoring Nutritional Advice for Mexicans Based on Prevalence Profiles of Diet-Related Adaptive Gene Polymorphisms

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Claudia Ojeda-Granados

2017-11-01

Full Text Available Diet-related adaptive gene (DRAG polymorphisms identified in specific populations are associated with chronic disorders in carriers of the adaptive alleles due to changes in dietary and lifestyle patterns in recent times. Mexico’s population is comprised of Amerindians (AM and Mestizos who have variable AM, European (EUR and African genetic ancestry and an increased risk of nutrition-related chronic diseases. Nutritional advice based on the Mexican genome and the traditional food culture is needed to develop preventive and therapeutic strategies. Therefore, we aimed to provide a prevalence profile of several DRAG polymorphisms in the Mexican population, including Central West (CW Mexico subpopulations. Geographic heat maps were built using ArcGIS10 (Esri, Redlands, CA, USA software, based on the published data of the MTHFR C677T (rs1801133, ABCA1 Arg230Cys (rs9282541, APOE T388C (rs429358/C526T (rs7412, LCT C-13910T (rs4988235 polymorphisms and AMY1 copy number variation (CNV. Also, new data obtained by allelic discrimination-real-time polymerase chain reaction (RT-PCR assays for the MTHFR, ABCA1, and APOE polymorphisms as well as the AMY1 CNV in the CW Mexico subpopulations with different proportions of AM and EUR ancestry were included. In the CW region, the highest frequency of the MTHFR 677T, ABCA1 230C and APOE ε4 adaptive alleles was observed in the AM groups, followed by Mestizos with intermediate AM ancestry. The LCT-13910T allele frequency was highest in Mestizos-EUR but extremely low in AM, while the AMY1 diploid copy number was 6.82 ± 3.3 copies. Overall, the heat maps showed a heterogeneous distribution of the DRAG polymorphisms, in which the AM groups revealed the highest frequencies of the adaptive alleles followed by Mestizos. Given these genetic differences, genome-based nutritional advice should be tailored in a regionalized and individualized manner according to the available foods and Mexican traditional food culture that

Genetic Polymorphisms in Endothelin-1 as Predictors for Long-Term Survival and the Cardiac Index in Patients Undergoing On-Pump Cardiac Surgery.

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Ashham Mansur

Full Text Available Genetic variants within the endothelin-1 gene (EDN1 have been associated with several cardiovascular diseases and may act as genetic prognostic markers. Here, we explored the overall relevance of EDN1 polymorphisms for long-term survival in patients undergoing on-pump cardiac surgery. A prospectively collected cohort of 455 Caucasian patients who underwent cardiac surgery with cardiopulmonary bypass was followed up for 5 years. The obtained genotypes and inferred haplotypes were analyzed for their associations with the five-year mortality rate (primary endpoint. The EDN1 T-1370G and K198N genotype distributions did not deviate from Hardy-Weinberg equilibrium and the major allele frequencies were 83% and 77%, respectively. The cardiovascular risk factors were equally distributed in terms of the different genotypes and haplotypes associated with the two polymorphisms. The five-year mortality rate did not differ among the different EDN1 T-1370G and K198N genotypes and haplotypes. Haplotype analysis revealed that carriers of the G-T (compound EDN1 T-1370G G/K198N T haplotype had a higher cardiac index than did non-carriers (p = 0.0008; however, this difference did not reach significance after adjusting for multiple testing. The results indicate that common variations in EDN1 do not act as prognostic markers for long-term survival in patients undergoing on-pump cardiac surgery.

Impact of the Ile105Val Polymorphism of the Glutathione S-transferase P1 (GSTP1) Gene on Obesity and Markers of Cardiometabolic Risk in Young Adult Population.

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Chielle, E O; Trott, A; da Silva Rosa, B; Casarin, J N; Fortuna, P C; da Cruz, I B M; Moretto, M B; Moresco, R N

2017-05-01

The aim of the study was to investigate the association between Glutathione S-transferase P1 (GSTP1) gene polymorphism with obesity and markers of cardiometabolic risk. A cross-sectional study was carried out in individuals aged≥18 and ≤30 years. The study included 54 normal weight, 27 overweight and 68 obese volunteers. Anthropometric measurements and biochemical parameters were evaluated, the DNA was extracted from blood samples and polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was used to measure GSTP1 Ile 105 Val gene polymorphism of the study participants. Also, biochemical analysis and hormone assays were carried out. A positive association between GSTP1 polymorphism and obesity was observed on subjects carrying at least one G allele (AG and GG). GG genotype was found only in the obese group. The G allele carriers presented 2.4 times higher chance of obesity when compared to those with the AA genotype. These results were independent of sex and age. We suggest that despite a study in population regional (south of Brazil), the GSTP1 gene polymorphism may play a significant role in the increase of susceptibility of obesity and contribute to identify the cardiovascular risk in young adults. © Georg Thieme Verlag KG Stuttgart · New York.

Associations of common polymorphisms in GCKR with type 2 diabetes and related traits in a Han Chinese population: a case-control study

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Lu Daru

2011-05-01

Full Text Available Abstract Background Several studies have shown that variants in the glucokinase regulatory protein gene (GCKR were associated with type 2 diabetes and dyslipidemia. The purpose of this study was to examine whether tag single nucleotide polymorphisms (SNPs in the GCKR region were associated with type 2 diabetes and related traits in a Han Chinese population and to identify the potential mechanisms underlying these associations. Methods We investigated the association of polymorphisms in the GCKR gene with type 2 diabetes by employing a case-control study design (1118 cases and 1161 controls. Four tag SNPs (rs8179206, rs2293572, rs3817588 and rs780094 with pairwise r2 > 0.8 and minor allele frequency > 0.05 across the GCKR gene and its flanking regions were studied and haplotypes were constructed. Genotyping was performed by matrix-assisted laser desorption/ionization time-of-flight mass spectroscopy using a MassARRAY platform. Results The G alleles of GCKR rs3817588 and rs780094 were associated with an increased risk of type 2 diabetes after adjustment for year of birth, sex and BMI (OR = 1.24, 95% CI 1.08-1.43, p = 0.002 and OR = 1.22, 95% CI 1.07-1.38, p = 0.002, respectively. In the non-diabetic controls, the GG carriers of rs3817588 and rs780094 were nominally associated with a lower plasma triglyceride level compared to the AA carriers after adjustment for year of birth, sex and BMI (p for trend = 0.00004 and 0.03, respectively. Furthermore, the association of rs3817588 with plasma triglyceride level was still significant after correcting for multiple testing. Conclusions The rs3817588 A/G polymorphism of the GCKR gene was associated with type 2 diabetes and plasma triglyceride level in the Han Chinese population.

7 CFR 33.4 - Carrier.

Science.gov (United States)

2010-01-01

... 7 Agriculture 2 2010-01-01 2010-01-01 false Carrier. 33.4 Section 33.4 Agriculture Regulations of the Department of Agriculture AGRICULTURAL MARKETING SERVICE (Standards, Inspections, Marketing... ISSUED UNDER AUTHORITY OF THE EXPORT APPLE ACT Definitions § 33.4 Carrier. Carrier means any common or...

The COMT Val158 Met polymorphism as an associated risk factor for Alzheimer disease and mild cognitive impairment in APOE 4 carriers

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Borda Sandra

2009-09-01

Full Text Available Abstract Background The aim of this study is to examine the influence of the catechol-O-methyltranferase (COMT gene (polymorphism Val158 Met as a risk factor for Alzheimer's disease (AD and mild cognitive impairment of amnesic type (MCI, and its synergistic effect with the apolipoprotein E gene (APOE. A total of 223 MCI patients, 345 AD and 253 healthy controls were analyzed. Clinical criteria and neuropsychological tests were used to establish diagnostic groups. The DNA Bank of the University of the Basque Country (UPV-EHU (Spain determined COMT Val158 Met and APOE genotypes using real time polymerase chain reaction (rtPCR and polymerase chain reaction (PCR, and restriction fragment length polymorphism (RFLPs, respectively. Multinomial logistic regression models were used to determine the risk of AD and MCI. Results Neither COMT alleles nor genotypes were independent risk factors for AD or MCI. The high activity genotypes (GG and AG showed a synergistic effect with APOE ε4 allele, increasing the risk of AD (OR = 5.96, 95%CI 2.74-12.94, p In MCI patients such as synergistic effect was only found between AG and APOE ε4 allele (OR = 3.21 95%CI 1.56-6.63, p = 0.02 and was greater in men (OR = 5.88 95%CI 1.69-20.42, p Conclusion COMT (Val158 Met polymorphism is not an independent risk factor for AD or MCI, but shows a synergistic effect with APOE ε4 allele that proves greater in women with AD.

The polymorphism of dopamine receptor D4 (DRD4) and dopamine transporter (DAT) genes in the men with antisocial behaviour and mixed martial arts fighters.

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Cherepkova, Elena V; Maksimov, Vladimir N; Kushnarev, Alexandr P; Shakhmatov, Igor I; Aftanas, Lyubomir I

2017-09-12

Variable-number tandem repeat (VNTR) polymorphisms of DRD4 and DAT genes were studied in the Russian and Chechen men convicted of crimes, and two control groups comprised of the MMA fighters and a sample of general population. A group of MMA fighters included only the subjects without history of antisocial behaviour. DNA was isolated by phenol-chloroform extraction from the blood. Genotyping VNTR polymorphisms of the DRD4 and DAT genes were performed by PCR on published methods. Among those convicted of felonies and most grave crimes, carriers of DRD4 long alleles are found more frequently, similarly to the cohort of MMA fighters (lacking criminal record in both paternal lines). The 9/9 DAT genotype carriers are more frequently encountered among the habitual offenders. A frequency of the combination of the DRD4 genotype 4/7 and DAT genotype 10/10 is clearly higher among the convicts of violent crimes and the MMA fighters. One can speculate the presence of a 'controlled aggression' without a predisposition to pathological violence in the MMA fighters. Our study supports the hypothesis of genetic predisposition to different variants of extreme behaviour mediated by genetic determinants involved in the functioning of neuromediator systems including those controlling dopamine pathways.

Low-cost carriers fare competition effect

NARCIS (Netherlands)

Carmona Benitez, R.B.; Lodewijks, G.

2010-01-01

This paper examines the effects that low-cost carriers (LCC’s) produce when entering new routes operated only by full-service carriers (FSC’s) and routes operated by low-cost carriers in competition with full-service carriers. A mathematical model has been developed to determine what routes should

G-231A and G+70C polymorphisms of endothelin receptor type-A gene could affect the psoriasis area and severity index score and endothelin 1 levels

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Gökhan Okan

2015-01-01

Full Text Available Background: The etiopathogenesis of psoriasis has not been clearly elucidated although the role of chronic inflammation, imbalance between pro- and anti-inflammatory cytokines, and many immunological events have been established. Endothelin 1 (EDN1 and endothelin receptor type-A (EDNRA are implicated in the inflammatory process. The relationships between EDN1 and EDNRA polymorphisms with several diseases have been found. Aims and Objectives: This study examined the possible association of EDN1 (G5665T and T-1370G and EDNRA (G-231A and G + 70C single nucleotide polymorphisms (SNPs with the occurence of psoriasis, and evaluated the relationship between genotypes and clinical/laboratory manifestation of psoriasis. Materials and Methods: We analyzed genotype and allele distributions of the above-mentioned polymorphisms in 151 patients with psoriasis and 152 healthy controls by real-time PCR combined with melting curve analysis. Results: We did not find significant differences in the genotype and allele distributions of EDN1 T-1370G, EDNRA G-231A, and EDNRA G+70C polymorphisms between patients with psoriasis and healthy controls. Psoriasis area and severity index (PASI score of EDNRA -231 polymorphic A allele carrying subjects (AA and AA + AG was higher than that of wild homozygotes (P = 0.044 and P = 0.027, respectively. In addition, EDN1 levels in EDNRA+70 polymorphic C allele carriers (CC + CG were elevated when compared with GG genotype; however, the difference was at borderline significance (P = 0.05. Conclusion: Although there were no associations between studied polymorphisms and psoriasis susceptibility, the PASI score and EDN1 levels seem to be affected by EDNRA G-231A and G + 70C polymorphisms.

Estimating Motor Carrier Management Information System Crash File Underreporting from Carrier Records.

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2017-08-01

This FMCSA-sponsored research investigated the claim that motor carriers have a substantial number of crashes in their own records that are not contained in the Motor Carrier Management Information System (MCMIS) crash file. Based on the results of t...

Apolipoprotein E gene polymorphism and Alzheimer's disease in Chinese population: a meta-analysis

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Liu, Mengying; Bian, Chen; Zhang, Jiqiang; Wen, Feng

2014-03-01

The relationship between Apolipoprotein E (ApoE) genotype and the risk of Alzheimer's disease (AD) is relatively well established in Caucasians, but less established in other ethnicities. To examine the association between ApoE polymorphism and the onset of AD in Chinese population, we searched the commonly used electronic databases between January 2000 and November 2013 for relevant studies. Total 20 studies, including 1576 cases and 1741 controls, were retrieved. The results showed statistically significant positive association between risk factor ɛ4 allele carriers and AD in Chinese population (OR = 3.93, 95% CI = 3.37-4.58, P risk suffering from AD than controls in Chinese population. The results also provide a support for the protection effect of ApoE ɛ3 allele in developing AD.

Carrier transport uphill. I. General

DEFF Research Database (Denmark)

Rosenberg, T; Wilbrandt, W

1963-01-01

A quantitative treatment of a carrier pump operating with two carrier forms C and Z is presented. Asymmetric metabolic reactions are assumed to transform Z into C on one and C into Z on the other side of the membrane, establishing a carrier cycle. The kinetical consequences of this mechanism...

The brain-derived neurotrophic factor (BDNF) gene Val66Met polymorphism affects memory performance in older adults.

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Azeredo, Lucas A de; De Nardi, Tatiana; Levandowski, Mateus L; Tractenberg, Saulo G; Kommers-Molina, Julia; Wieck, Andrea; Irigaray, Tatiana Q; Silva, Irênio G da; Grassi-Oliveira, Rodrigo

2017-01-01

Memory impairment is an important contributor to the reduction in quality of life experienced by older adults, and genetic risk factors seem to contribute to variance in age-related cognitive decline. Brain-derived neurotrophic factor (BDNF) is an important nerve growth factor linked with development and neural plasticity. The Val66Met polymorphism in the BDNF gene has been associated with impaired episodic memory in adults, but whether this functional variant plays a role in cognitive aging remains unclear. The purpose of this study was to investigate the effects of the BDNF Val66Met polymorphism on memory performance in a sample of elderly adults. Eighty-seven subjects aged > 55 years were recruited using a community-based convenience sampling strategy in Porto Alegre, Brazil. The logical memory subset of the Wechsler Memory Scale-Revised was used to assess immediate verbal recall (IVR), delayed verbal recall (DVR), and memory retention rate. BDNF Met allele carriers had lower DVR scores (p = 0.004) and a decline in memory retention (p = 0.017) when compared to Val/Val homozygotes. However, we found no significant differences in IVR between the two groups (p = 0.088). These results support the hypothesis of the BDNF Val66Met polymorphism as a risk factor associated with cognitive impairment, corroborating previous findings in young and older adults.

Association of ABCB1 polymorphisms with the antiemetic efficacy of granisetron plus dexamethasone in breast cancer patients.

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Tsuji, Daiki; Kim, Yong-Il; Nakamichi, Hidenori; Daimon, Takashi; Suwa, Kaori; Iwabe, Yutaro; Hayashi, Hideki; Inoue, Kazuyuki; Yoshida, Masayuki; Itoh, Kunihiko

2013-01-01

Resistance to antiemetic treatment with 5-hydroxytryptamine 3 receptor antagonists is a problem, with 20-30% of patients showing unsatisfactory responses. Efflux transport by P-glycoprotein, encoded by the ATP-binding cassette ABCB1 gene in the blood-brain barrier, has been the suggested resistance mechanism. We evaluated the association between the antiemetic efficacy of granisetron plus dexamethasone and ABCB1 polymorphisms 3435C>T and 2677G>T/A. Sixty-four breast cancer patients treated with doxorubicin plus cyclophosphamide were evaluated for their responses to antiemetic therapy. Genotyping of patient DNA samples for ABCB1 single nucleotide polymorphisms was performed; the genotypes were then investigated for their association with the efficacy of prophylactic antiemetics. The acute phase complete response rate was 83% in GG subjects (n = 12), and 69% (n = 35) and 41% (n = 17) in heterozygous and homozygous carriers of the 2677T/A allele, respectively (p = 0.047). The ABCB1 2677 TT genotype group showed significantly lower rates of complete control of acute emesis than the group with GG genotypes (p = 0.045). No significant association with complete response was found for 3435C>T (p = 0.190). ABCB1 polymorphisms may influence the extent of acute emesis control in granisetron-treated patients, making the ABCB1 genotype a predictor of prophylactic antiemetic response.

Association of IL-6 and CRP gene polymorphisms with obesity and metabolic disorders in children and adolescents

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Pâmela F. Todendi

2015-06-01

Full Text Available Activation of adipose tissue inflammation is associated with obesity caused by lipid accumulation in adipocytes. Through this activation, proinflammatory cytokines, such as Interleukin-6 (IL-6 and C-reactive protein (CRP seem to influence metabolic disorders. The present study evaluated whether polymorphisms in the CRP (rs1205 and IL-6 (rs1800795, rs2069845 genes are associated with the development of metabolic disorders in children and adolescents. A cross-sectional study was performed, consisting of 470 students from the municipality of Santa Cruz do Sul, Brazil, aged 7-17 years. Body mass index (BMI was classified according to overweight and obesity. Genotyping was performed by real-time Polymerase Chain Reaction(PCR. Anthropometric characteristics, biochemical markers, immunological markers and blood pressure were assessed. Descriptive statistics, chi-square and logistic regression were used for the analyses. No association was detected between the rs1800795 polymorphism and the assessed variables. Individuals with the risk genotype in the rs1205 gene were associated with the risk of developing hypercholesterolemia (OR 2.79; CI 1.40, 5.57; p = 0.003. Carriers of the risk genotype in the rs2069845 gene are associated with the risk of developing obesity (OR 3.07; CI 1.08, 8.72; p = 0.03. The polymorphism rs2069845 was associated with obesity and rs1205 was associated with the risk of developing hypercholesterolemia in Brazilian schoolchildren.

The brain-derived neurotrophic factor (BDNF gene Val66Met polymorphism affects memory performance in older adults

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Lucas A. de Azeredo

Full Text Available Objective: Memory impairment is an important contributor to the reduction in quality of life experienced by older adults, and genetic risk factors seem to contribute to variance in age-related cognitive decline. Brain-derived neurotrophic factor (BDNF is an important nerve growth factor linked with development and neural plasticity. The Val66Met polymorphism in the BDNF gene has been associated with impaired episodic memory in adults, but whether this functional variant plays a role in cognitive aging remains unclear. The purpose of this study was to investigate the effects of the BDNF Val66Met polymorphism on memory performance in a sample of elderly adults. Methods: Eighty-seven subjects aged > 55 years were recruited using a community-based convenience sampling strategy in Porto Alegre, Brazil. The logical memory subset of the Wechsler Memory Scale-Revised was used to assess immediate verbal recall (IVR, delayed verbal recall (DVR, and memory retention rate. Results: BDNF Met allele carriers had lower DVR scores (p = 0.004 and a decline in memory retention (p = 0.017 when compared to Val/Val homozygotes. However, we found no significant differences in IVR between the two groups (p = 0.088. Conclusion: These results support the hypothesis of the BDNF Val66Met polymorphism as a risk factor associated with cognitive impairment, corroborating previous findings in young and older adults.

Generation of Hypertension-Associated STK39 Polymorphism Knockin Cell Lines With the Clustered Regularly Interspaced Short Palindromic Repeats/Cas9 System.

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Mandai, Shintaro; Mori, Takayasu; Sohara, Eisei; Rai, Tatemitsu; Uchida, Shinichi

2015-12-01

Previous genome-wide association studies identified serine threonine kinase 39 (STK39), encoding STE20/SPS1-related proline/alanine-rich kinase, as one of a limited number of hypertension susceptibility genes. A recent meta-analysis confirmed the association of STK39 intronic polymorphism rs3754777 with essential hypertension, among previously reported hypertension-associated STK39 polymorphisms. However, the biochemical function of this polymorphism in the mechanism responsible for hypertension is yet to be clarified. We generated rs3754777G>A knockin human cell lines with clustered regularly interspaced short palindromic repeats-mediated genome engineering. Homozygous (A/A) and heterozygous (G/A) knockin human embryonic kidney cell lines were generated using a double nickase, single-guide RNAs targeting STK39 intron 5 around single-nucleotide polymorphism, and a 100-bp donor single-stranded DNA oligonucleotide. Reverse transcription polymerase chain reaction with sequencing analyses revealed the identical STK39 transcripts among the wild-type and both knockin cell lines. Quantitative reverse transcription polymerase chain reaction showed increased STK39 mRNA expression, and immunoblot analysis revealed increases in total and phosphorylated STE20/SPS1-related proline/alanine-rich kinase with increased phosphorylated Na-K-Cl cotransporter isoform 1 in both knockin cell lines. The largest increases in these molecules were observed in the homozygous cell line. These findings indicated that this intronic polymorphism increases STK39 transcription, leading to activation of the STE20/SPS1-related proline/alanine-rich kinase-solute carrier family 12A signaling cascade. Increased interactions between STE20/SPS1-related proline/alanine-rich kinase and the target cation-chloride cotransporters may be responsible for hypertension susceptibility in individuals with this polymorphism. © 2015 American Heart Association, Inc.

Inert carriers for column extraction chromatography

International Nuclear Information System (INIS)

Katykhin, G.S.

1978-01-01

Inert carriers used in column extraction chromatography are reviewed. Such carriers are devided into two large groups: hydrophilic carriers which possess high surface energy and are well wetted only with strongly polar liquids (kieselguhrs, silica gels, glasses, cellulose, Al 2 O 3 ) and water-repellent carriers which possess low surface energy and are well wetted with various organic solvents (polyethylene, polytetrafluorethylene polytrifluorochlorethylene). Properties of various carriers are presented: structure, chemical and radiation stability, adsorption properties, extracting agent capacity. The effect of structure and sizes of particles on the efficiency of chromatography columns is considered. Ways of immovable phase deposition on the carrier and the latter's regeneration. Peculiarities of column packing for preparative and continuous chromatography are discussed

Association of the matrix metalloproteinase-3 polymorphisms rs679620 and rs3025058 with ischemic stroke risk: a meta-analysis

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Zhang Q

2018-01-01

Full Text Available Qi-Wei Zhang Department of Neurosurgery, The Affiliated Hospital of Jilin Medical University, Jilin, People’s Republic of China Purpose: The relationship of the matrix metalloproteinase-3 (MMP-3 polymorphisms rs679620 and rs3025058 with ischemic stroke has received much attention. The aim of the present study was to perform a meta-analysis of published case–control studies to evaluate the cumulative evidence.Methods: We performed a search of ISI Web of Science, Embase, PubMed, and China National Knowledge Infrastructure databases. Pooled odds ratios (ORs were appropriately derived from fixed-effects or random-effects models.Results: We identified seven eligible studies including 5,204 subjects. The pooled analysis showed that the MMP-3 rs679620 A allele carriers had increased risk of ischemic stroke compared with homozygotes for the G allele in Asians (AA + GA vs GG: OR =1.42, 95% CI: 1.05–1.91, P=0.022. Concerning the rs3025058 polymorphism, the results did not suggest an association between rs3025058 genotypes and ischemic stroke risk (5A5A + 6A5A vs 6A6A: OR =1.04, 95% CI: 0.73–1.47, P=0.844; 5A5A vs 6A5A + 6A6A: OR =1.14, 95% CI: 0.74–1.77, P=0.556; and 5A5A vs 6A6A: OR =1.11, 95% CI: 0.68–1.80, P=0.677. In subgroup analysis by ethnicity, no statistically significant associations were demonstrated for rs3025058 in Asians and Caucasians, respectively. There was no evidence for publication bias.Conclusion: Our findings indicate that the rs679620 A allele carriers have increased risk of ischemic stroke in Asians, but there is no association between rs3025058 and ischemic stroke risk. Keywords: ischemic stroke, meta-analysis, MMP-3, polymorphism

Interaction between polymorphisms of the Human Leukocyte Antigen and HPV-16 Variants on the risk of invasive cervical cancer

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Araujo Souza, Patricia S de; Maciag, Paulo C; Ribeiro, Karina B; Petzl-Erler, Maria Luiza; Franco, Eduardo L; Villa, Luisa L

2008-01-01

Persistent infection with oncogenic types of human papillomavirus (HPV) is the major risk factor for invasive cervical cancer (ICC), and non-European variants of HPV-16 are associated with an increased risk of persistence and ICC. HLA class II polymorphisms are also associated with genetic susceptibility to ICC. Our aim is to verify if these associations are influenced by HPV-16 variability. We characterized HPV-16 variants by PCR in 107 ICC cases, which were typed for HLA-DQA1, DRB1 and DQB1 genes and compared to 257 controls. We measured the magnitude of associations by logistic regression analysis. European (E), Asian-American (AA) and African (Af) variants were identified. Here we show that inverse association between DQB1*05 (adjusted odds ratio [OR] = 0.66; 95% confidence interval [CI]: 0.39–1.12]) and HPV-16 positive ICC in our previous report was mostly attributable to AA variant carriers (OR = 0.27; 95%CI: 0.10–0.75). We observed similar proportions of HLA DRB1*1302 carriers in E-P positive cases and controls, but interestingly, this allele was not found in AA cases (p = 0.03, Fisher exact test). A positive association with DRB1*15 was observed in both groups of women harboring either E (OR = 2.99; 95% CI: 1.13–7.86) or AA variants (OR = 2.34; 95% CI: 1.00–5.46). There was an inverse association between DRB1*04 and ICC among women with HPV-16 carrying the 350T [83L] single nucleotide polymorphism in the E6 gene (OR = 0.27; 95% CI: 0.08–0.96). An inverse association between DQB1*05 and cases carrying 350G (83V) variants was also found (OR = 0.37; 95% CI: 0.15–0.89). Our results suggest that the association between HLA polymorphism and risk of ICC might be influenced by the distribution of HPV-16 variants

Evidences of +896 A/G TLR4 Polymorphism as an Indicative of Prevalence of Complications in T2DM Patients

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Carmela Rita Balistreri

2014-01-01

Full Text Available T2DM is today considered as world-wide health problem, with complications responsible of an enhanced mortality and morbidity. Thus, new strategies for its prevention and therapy are necessary. For this reason, the research interest has focused its attention on TLR4 and its polymorphisms, particularly the rs4986790. However, no conclusive findings have been reported until now about the role of this polymorphism in development of T2DM and its complications, even if a recent meta-analysis showed its T2DM association in Caucasians. In this study, we sought to evaluate the weight of rs4986790 polymorphism in the risk of the major T2DM complications, including 367 T2DM patients complicated for the 55.6%. Patients with A/A and A/G TLR4 genotypes showed significant differences in complication’s prevalence. In particular, AG carriers had higher risk prevalence for neuropathy (P=0.026, lower limb arteriopathy (P=0.013, and the major cardiovascular pathologies (P=0.017. Their cumulative risk was significant (P=0.01, with a threefold risk to develop neuropathy, lower limb arteriopathy, and major cardiovascular events in AG cases compared to AA cases. The adjusted OR for the confounding variables was 3.788 (95% CI: 1.642–8.741. Thus, the rs4986790 polymorphism may be an indicative of prevalence of complications in T2DM patients.

TPC2 polymorphisms associated with a hair pigmentation phenotype in humans result in gain of channel function by independent mechanisms.

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Chao, Yu-Kai; Schludi, Verena; Chen, Cheng-Chang; Butz, Elisabeth; Nguyen, O N Phuong; Müller, Martin; Krüger, Jens; Kammerbauer, Claudia; Ben-Johny, Manu; Vollmar, Angelika M; Berking, Carola; Biel, Martin; Wahl-Schott, Christian A; Grimm, Christian

2017-10-10

Two-pore channels (TPCs) are endolysosomal cation channels. Two members exist in humans, TPC1 and TPC2. Functional roles associated with the ubiquitously expressed TPCs include VEGF-induced neoangiogenesis, LDL-cholesterol trafficking and degradation, physical endurance under fasting conditions, autophagy regulation, the acrosome reaction in sperm, cancer cell migration, and intracellular trafficking of pathogens such as Ebola virus or bacterial toxins (e.g., cholera toxin). In a genome-wide association study for variants associated with human pigmentation characteristics two coding variants of TPC2, rs35264875 (encoding M484L) and rs3829241 (encoding G734E), have been found to be associated with a shift from brown to blond hair color. In two recent follow-up studies a role for TPC2 in pigmentation has been further confirmed. However, these human polymorphic variants have not been functionally characterized until now. The development of endolysosomal patch-clamp techniques has made it possible to investigate directly ion channel activities and characteristics in isolated endolysosomal organelles. We applied this technique here to scrutinize channel characteristics of the polymorphic TPC2 variants in direct comparison with WT. We found that both polymorphisms lead to a gain of channel function by independent mechanisms. We next conducted a clinical study with more than 100 blond- and brown/black-haired individuals. We performed a genotype/phenotype analysis and subsequently isolated fibroblasts from WT and polymorphic variant carriers for endolysosomal patch-clamp experimentation to confirm key in vitro findings.

Cigarettes, genetic background, and menopausal timing: the presence of single nucleotide polymorphisms in cytochrome P450 genes is associated with increased risk of natural menopause in European-American smokers.

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Butts, Samantha F; Sammel, Mary D; Greer, Christine; Rebbeck, Timothy R; Boorman, David W; Freeman, Ellen W

2014-07-01

This study aims to evaluate associations between variations in genes involved in the metabolism of environmental chemicals and steroid hormones and risk of menopause in smokers. Survival analysis was performed on 410 eligible participants from the Penn Ovarian Aging study (ongoing for 14 years), a cohort study of late-reproductive-age women. Single nucleotide polymorphisms at the following loci were studied: COMT Val158Met, CYP1B1*4 Asn452Ser, CYP1B1*3 Leu432Val, and CYP3A4*1B. Significant interactions between smoking and single nucleotide polymorphisms were observed in European-American carriers of CYP3A4*1B and CYP1B1*3, supporting a greater risk of menopause entry compared with those not carrying these alleles. Among CYP1B1*3 carriers, smokers had a greater risk of menopause entry than nonsmokers (adjusted hazard ratio [HR], 2.26; 95% CI, 1.4-3.67; median time to menopause, 10.42 and 11.07 y, respectively). No association between smoking and menopause was identified in CYP1B1 wild types. Among CYP3A4*1B carriers, smokers were at greater risk for menopause entry than nonsmokers (adjusted HR, 15.1; 95% CI, 3.31-69.2; median time to menopause, 11.36 and 13.91 y, respectively). Risk of menopause entry in CYP3A4 wild types who smoked was far lower (adjusted HR, 1.59; 95% CI, 1.03-2.44). Heavily smoking CYP1B1*3 carriers (adjusted HR, 3.0; 95% CI, 1.54-5.84; median time to menopause, 10.41 y) and heavily smoking CYP3A4*1B carriers (adjusted HR, 17.79; 95% CI, 3.21-98.65; median time to menopause, 5.09 y) had the greatest risk of menopause entry. Our finding that the risk of menopause entry in European-American smokers varies depending on genetic background represents a novel gene-environment interaction in reproductive aging.

The Plasminogen Activator Inhibitor 1 4G/5G Polymorphism and the Risk of Alzheimer's Disease.

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Fekih-Mrissa, Najiba; Mansour, Malek; Sayeh, Aicha; Bedoui, Ines; Mrad, Meriem; Riahi, Anis; Mrissa, Ridha; Nsiri, Brahim

2017-09-01

The aim of this study was to determine whether plasminogen activator inhibitor 1 (PAI-1) is associated with the risk of Alzheimer's disease (AD) in Tunisian patients. We analyzed the genotype and allele frequency distribution of the PAI-1 polymorphism in 60 Tunisian patients with AD and 120 healthy controls. The results show a significantly increased risk of AD in carriers of the 4G/4G and 4G/5G genotypes versus the wild-type 5G/5G genotype (4G/4G: 28.33% in patients vs 10.0% in controls; P 5G: 55.0% in patients vs 38.33% in controls; OR = 4.45; P < 10 -3 ). The 4G allele was also more frequently found in patients compared with controls; P < 10 -3 ; OR = 3.07. For all participants and by gender, homozygotic carriers (4G/4G) were at an increased risk of AD over heterozygotes and women were at an increased risk over their male genotype counterparts. The odds ratio for AD among 4G/4G carriers for any group was approximately twice that of heterozygotes in the same group. Women homozygotes ranked highest for AD risk (OR = 20.8) and, in fact, women heterozygotes (OR = 9.03) ranked higher for risk than male homozygotes (OR = 6.12). These preliminary exploratory results should be confirmed in a larger study.

The relationship between CA repeat polymorphism of the IGF-1 gene and the structure of motor skills in young athletes.

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Karpowicz, Krzysztof; Krych, Katarzyna; Karpowicz, Małgorzata; Nowak, Witold; Gronek, Piotr

2018-01-01

The map of candidate genes that can potentially affect physical fitness becomes larger every year, and they are associated with such aspects as respiratory and cardiovascular stability; body build and composition - especially muscle mass and strength; carbohydrate and lipid metabolism; response to training; and exercise intolerance.The aim of this study was to analyze the relationship between the CA repeat polymorphism of the P1 promoter of the IGF1 gene and the structure of motor skills in the two groups of Polish young athletes in 2007-2009. In this study, 350 young sportsmen representing different sports disciplines were examined (age = 15.5 ± 0.5 years), by genotyping the IGF1 gene and determining the structure of motor skills using the International Physical Fitness Test (IPFT) battery. The multiple stepwise regression was used to determine the impact of the investigated motor skills on the indicator of the overall physical fitness, measured by the total score of the International Physical Fitness Test (IPFT). The analysis showed some regularity related to the character of the IGF1 gene polymorphism. It can be concluded that the two groups of young boys athletes practicing various sports disciplines (kinds of physical exercise) displayed similar associations between CA repeat polymorphism of the P1 promoter of the IGF1 gene and the level of motor effects. Our results suggest that this polymorphism may be a genetic marker of the physical performance phenotype. We demonstrated that CA repeat polymorphism of the P1 promoter of the IGF1 gene was associated with strength predispositions in the homozygous and non-carriers groups. In the group who were heterozygous it was speed-strength aptitudes.

The Common Acid Sphingomyelinase Polymorphism p.G508R is Associated with Self-Reported Allergy

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Martin Reichel

2014-06-01

Full Text Available Background: Acid sphingomyelinase (ASM is a key regulator of ceramide-dependent signalling pathways. Among others, activation of ASM can be induced by CD95 or cytokine signalling and by cellular stress resulting from inflammation or infection. Increased ASM activity was observed in a variety of human diseases including inflammatory and neuropsychiatric disorders. We hypothesized that basal ASM activity might influence the susceptibility for common human diseases. Methods: The general health condition of 100 young people was assessed using a questionnaire. The ASM polymorphism rs1050239 (c.1522G>A; encoding p.G508R was determined from genomic DNA. Activities of secretory (S- and lysosomal (L- ASM were measured in blood plasma and peripheral blood cells respectively. Results: The polymorphism rs1050239 was significantly associated with self-reported allergy (p=4.68×10-4; adjusted p-value for multiple testing 0.007. Allergy was more prevalent in carriers of the minor A allele compared to non-carriers (p=0.00015; odds ratio=6.5, 95% CI 2.15-21.7. S-ASM activity was significantly associated with rs1050239 (p=5.3×10-7 and decreased with the number of A alleles in a gene-dosage dependent manner. In allergic patients, S-ASM activity was moderately decreased (p=0.034. L-ASM activity was significantly lower in subjects homozygous for the minor A allele (p=0.025 but not different between allergic and non-allergic subjects (p=0.318. Conclusion: Our analysis provides evidence for an involvement of ASM in the pathophysiology of allergy, which is in line with previous reports addressing the role of sphingolipids in this disorder. Further studies should clarify the mechanism linking rs1050239 to allergy. The ASM pathway might be useful for predicting allergic disposition and disease course and as a therapeutic target.

The rs10757278 Polymorphism of the 9p21.3 Locus in Children with Arterial Ischemic Stroke: A Family-Based and Case-Control Study.

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Niemiec, Pawel; Balcerzyk, Anna; Iwanicki, Tomasz; Emich-Widera, Ewa; Kopyta, Ilona; Nowak, Tomasz; Pilarska, Ewa; Pienczk-Ręcławowicz, Karolina; Kaciński, Marek; Wendorff, Janusz; Gorczynska-Kosiorz, Sylwia; Trautsolt, Wanda; Grzeszczak, Władysław; Zak, Iwona

2017-12-01

The association of 9p21.3 locus single nucleotide polymorphisms with arterial ischemic stroke in adults was demonstrated in many studies, but there are no studies in pediatric arterial ischemic stroke patients. We investigated whether the 9p21.3 locus polymorphism, namely rs10757278, is associated with the arterial ischemic stroke risk in children. The study group consisted of 335 individuals: 80 children with arterial ischemic stroke, their biological parents (n = 122), and 133 children (age and sex matched) without any symptoms of arterial ischemic stroke as a control group. The rs10757278 polymorphism was genotyped using the TaqMan® Pre-designed SNP Genotyping Assay (Applied Biosystems). Two different study design models were used: family-based association test (transmission-disequilibrium test) and case-control model. There were no statistically significant differences in the distribution of genotypes and alleles of the rs10757278 polymorphism between groups of children with arterial ischemic stroke and controls. The frequency of both transmitted alleles in transmission-disequilibrium test analysis was identical (50%). The A allele carrier state (AA+AG genotype) was more frequent in arterial ischemic stroke children with hemiparesis than in patients without this symptom (94.5% versus 68.0%, P = .004). There is no evidence to consider the 9p21.3 locus polymorphism as a risk factor for childhood arterial ischemic stroke. Copyright © 2017 National Stroke Association. Published by Elsevier Inc. All rights reserved.

PvuII and XbaI polymorphisms of estrogen receptor-α and the results of estroprogestagen therapy in girls with functional hypothalamic amenorrhea - preliminary study.