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Sample records for pthr1 polymorphisms influence

  1. PTHR1 polymorphisms influence BMD variation through effects on the growing skeleton

    DEFF Research Database (Denmark)

    Vilariño-Güell, Carles; Miles, Lisa J; Duncan, Emma L

    2007-01-01

    . A cohort of 634 families, including 1,236 men (39%) and 1,926 women (61%) ascertained with probands with low BMD (Z... most informative SNPs (minor allele frequency >5%) and the tetranucleotide repeat. In our osteoporosis families, association was noted between lumbar spine BMD and alleles of a known functional tetranucleotide repeat (U4) in the PTHR1 promoter region (P = 0.042) and between two and three marker...... haplotypes of PTHR1 polymorphisms with lumbar spine, femoral neck, and total hip BMD (P = 0.021-0.047). This association was restricted to the youngest tertile of the population (age 16-39 years, P = 0.013-0.048). A similar association was found for the ALSPAC cohort: two marker haplotypes of SNPs A48609T...

  2. Recessive mutations in PTHR1 cause contrasting skeletal dysplasias in Eiken and Blomstrand syndromes

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    Duchatelet, Sabine; Ostergaard, Elsebet; Cortes, Dina

    2005-01-01

    Eiken syndrome is a rare autosomal recessive skeletal dysplasia. We identified a truncation mutation in the C-terminal cytoplasmic tail of the parathyroid hormone (PTH)/PTH-related peptide (PTHrP) type 1 receptor (PTHR1) gene as the cause of this syndrome. Eiken syndrome differs from Jansen...

  3. Influence of shock induced polymorphic transition on penetration in steel

    International Nuclear Information System (INIS)

    Hereil, P.L.; Fanget, A.

    1994-01-01

    The effects of polymorphic transition for the impact of a 27NCD10 steel projectile on a 27NCD10 steel target at 1280 m/s is presented. Comparisons between results of 2D numerical calculations performed with and without polymorphic transition show the influence of this phenomenon on stress distribution and tension zones in the target and in the projectile. Good agreement between experimental and calculated free surface velocity profiles is obtained with polymorphic transition and damage models taken into account. (orig.)

  4. Polymorphisms in melatonin synthesis pathways: possible influences on depression

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    McCarthy Michael J

    2011-08-01

    Full Text Available Abstract Background It has been reported that rs4446909, a single nucleotide polymorphism (SNP in the promoter of acetylserotonin methyltransferase (ASMT, influences the expression of the ASMT enzyme. The common G allele is associated with lower ASMT activity, and therefore, diminishes conversion of N-acetylserotonin to melatonin. The G allele was associated with recurrent depressive disorder in a Polish group. ASMT might also affect bipolar relapse, given evidence that N-acetylserotonin might stimulate TRKB receptors, and TRKB may influence mood relapse in bipolar disorder. Additionally, arylalkylamine N-acetyltransferase (AANAT polymorphisms have been reported associated with depression, perhaps through their influence upon N-acetylserotonin or melatonin synthesis. Results To replicate and further explore these ideas, rs4446909 was genotyped in four research groups, as part of a panel of 610 SNPs surveyed by an Illumina Golden Gate assay. In 768 cases with delayed sleep phase disorder or matched controls, rs4446909 was indeed associated with the depressive symptoms on a self-report scale (P = 0.01, R2 = 0.007. However, there was no significant association of rs4446909 with self-reported depression in a sleep clinic patient group or with two groups of elderly men and women from multicenter studies, nor was the response to lithium treatment associated with rs4446909 in bipolar patients. No associations of two AANAT SNPs with depression were found. Conclusions The evidence did not support a strong influence of rs4446909 upon mood, but the partial replication may be consistent with a modest effect. It is possible that larger or younger subject groups with improved phenotype ascertainment might demonstrate more persuasive replication.

  5. Influence of FCGRT gene polymorphisms on pharmacokinetics of therapeutic antibodies.

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    Passot, Christophe; Azzopardi, Nicolas; Renault, Sylvaine; Baroukh, Nadine; Arnoult, Christophe; Ohresser, Marc; Boisdron-Celle, Michèle; Gamelin, Erick; Watier, Hervé; Paintaud, Gilles; Gouilleux-Gruart, Valérie

    2013-01-01

    The neonatal Fc receptor (FcRn) encoded by FCGRT is known to be involved in the pharmacokinetics (PK) of therapeutic monoclonal antibodies (mAbs). Variability in the expression of FCGRT gene and consequently in the FcRn protein level could explain differences in PK observed between patients treated with mAbs. We studied whether the previously described variable number tandem repeat (VNTR) or copy number variation (CNV) of FCGRT are associated with individual variations of PK parameters of cetuximab. VNTR and CNV were assessed on genomic DNA of 198 healthy individuals and of 94 patients treated with the therapeutic mAb. VNTR and CNV were analyzed by allele-specific PCR and duplex real-time PCR with Taqman (®) technology, respectively. The relationship between FCGRT polymorphisms (VNTR and CNV) and PK parameters of patients treated with cetuximab was studied. VNTR3 homozygote patients had a lower cetuximab distribution clearance than VNTR2/VNTR3 and VNTR3/VNTR4 patients (p = 0.021). We observed no affects of VNTR genotype on elimination clearance. One healthy person (0.5%) and 1 patient (1.1%) had 3 copies of FCGRT. The PK parameters of this patient did not differ from those of patients with 2 copies. The FCGRT promoter VNTR may influence mAbs' distribution in the body. CNV of FCGRT cannot be used as a relevant pharmacogenetic marker because of its low frequency.

  6. Polymorphisms influencing expression of dermonecrotic toxin in Bordetella bronchiseptica.

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    Keisuke Okada

    Full Text Available Bordetella bronchiseptica is a pathogenic bacterium causing respiratory infections in a broad range of mammals. Recently, we determined the whole genome sequence of B. bronchiseptica S798 strain isolated from a pig infected with atrophic rhinitis and found four single-nucleotide polymorphisms (SNPs at positions -129, -72, +22, and +38 in the region upstream of dnt encoding dermonecrotic toxin (DNT, when compared with a rabbit isolate, RB50. DNT is known to be involved in turbinate atrophy observed in atrophic rhinitis. Immunoblotting, quantitative real-time PCR, and β-galactosidase reporter assay revealed that these SNPs resulted in the increased promoter activity of dnt and conferred the increased ability to produce DNT on the bacteria. Similar or identical SNPs were also found in other pig isolates kept in our laboratory, all of which produce a larger amount of DNT than RB50. Our analysis revealed that substitution of at least two of the four bases, at positions -72 and +22, influenced the promoter activity for dnt. These results imply that these SNPs are involved in the pathogenicity of bordetellae specific to pig diseases.

  7. Influence of BDNF and COMT polymorphisms on emotional decision making.

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    Kang, Jee In; Namkoong, Kee; Ha, Ra Yeon; Jhung, Kyungun; Kim, Yang Tae; Kim, Se Joo

    2010-06-01

    Decision making is an important brain function. Although little is known about the genetic basis of decision making, it has been suggested that it is mediated by the modulation of neurotransmitter systems. We investigated how the BDNF Val66Met and COMT Val158Met polymorphisms affect emotional decision making using the Iowa Gambling Task (IGT). One hundred sixty-eight healthy Korean college students (93 males, 75 females) with a complete dataset were included in the data analysis. The IGT and genotyping for the polymorphisms of BDNF Val66Met and COMT Val158Met were performed. Both Met/Met and Val/Met of the BDNF Val66Met polymorphism were significantly associated with a lower mean score of blocks 3-5 of the IGT and with less improvement from block 1 to block 3-5 than the Val/Val. However, the BDNF was not significantly associated with the score of block 1, and the COMT Val158Met polymorphism produced no significant effect on IGT performance. No interaction effect was observed between the BDNF and the COMT for the IGT. These findings suggest the BDNF Val66Met may affect the emotional decision making performance. (c) 2010 Elsevier Ltd. All rights reserved.

  8. Count on dopamine: influences of COMT polymorphisms on numerical cognition

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    Annelise eJúlio-Costa

    2013-08-01

    Full Text Available Catechol-O-methyltransferase (COMT is an enzyme that is particularly important for the metabolism of dopamine. Functional polymorphisms of COMT have been implicated in working memory and numerical cognition. This is an exploratory study that aims at investigating associations between COMT polymorphisms, working memory and numerical cognition. Elementary school children from 2th to 6th grades were divided into two groups according to their COMT val158met polymorphism (homozygous for valine allele [n= 61] versus heterozygous plus methionine homozygous children or met+ group [n=94]. Both groups were matched for age and intelligence. Working memory was assessed through digit span and Corsi blocks. Symbolic numerical processing was assessed through transcoding and single-digit word problem tasks. Non-symbolic magnitude comparison and estimation tasks were used to assess number sense. Between-group differences were found in symbolic and non-symbolic numerical tasks, but not in working memory tasks. Children in the met+ group showed better performance in all numerical tasks while val homozygous children presented slower development of non-symbolic magnitude representations. These results suggest COMT-related dopaminergic modulation may be related not only to working memory, as found in previous studies, but also to the development of magnitude processing and magnitude representations.

  9. Influence of CAG Repeat Polymorphism on the Targets of Testosterone Action

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    Giacomo Tirabassi

    2015-01-01

    Full Text Available In the last decade, ample evidence has demonstrated the growing importance of androgen receptor (AR CAG repeat polymorphism in andrology. This genetic parameter is able to condition the peripheral effects of testosterone and therefore to influence male sexual function and fertility, cardiovascular risk, body composition, bone metabolism, the risk of prostate and testicular cancer, the psychiatric status, and the onset of neurodegenerative disorders. In this review, we extensively discuss the literature data and identify a role for AR CAG repeat polymorphism in conditioning the systemic testosterone effects. In particular, our main purpose was to provide an updated text able to shed light on the many and often contradictory findings reporting an influence of CAG repeat polymorphism on the targets of testosterone action.

  10. Influence of leukotriene gene polymorphisms on chronic rhinosinusitis

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    Duval Melanie

    2008-03-01

    Full Text Available Abstract Background Chronic rhinosinusitis (CRS is increasingly viewed as an inflammatory condition of the sinonasal mucosa interacting with bacteria and/or fungi. However, factors conferring susceptibility to disease remain unknown. Advances in genomics offer powerful tools to explore this disorder. The goal of this study was to evaluate the effect of single nucleotide polymorphisms (SNP on CRS in a panel of genes related to cysteinyl leukotriene metabolism. Methods Severe cases of CRS and postal code match controls were recruited prospectively. A total of 206 cases and 200 controls were available for the present study. Using a candidate gene approach, five genes related to cysteinyl leukotriene metabolism were assessed. For each gene, we selected the maximally informative set of common SNPs (tagSNPs using the European-derived (CEU HapMap dataset. These SNPs are in arachidonate 5-lipoxygenase (ALOX5, arachidonate 5-lipoxygenase-activating protein (ALOX5AP, leukotriene C4 synthase (LTC4S, cysteinyl leukotriene receptor 1 (CYSLTR1 and cysteinyl leukotriene receptor 2 (CYSLTR2 genes. Results A total of 59 SNPs were genotyped to capture the common genetic variations within these genes. Three SNPs located within the ALOX5, CYSLTR1 and ALOX5AP genes reached the nominal p-value threshold (p Conclusion While these initial results do not support that polymorphsims in genes assessed involved in the leukotriene pathways are contributing to the pathogenesis of CRS, this initial study was not powered to detect polymorphisms with relative risk of 2.0 or less, where we could expect many gene effects for complex diseases to occur. Thus, despite this lack of significant association noted in this study, we believe that validation with external populations and the use of better-powered studies in the future may allow more conclusive findings.

  11. Depression, the Val66Met polymorphism, age, and gender influence the serum BDNF level

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    Elfving, Betina; Buttenschøn, Henriette Nørmølle; Foldager, Leslie

    2012-01-01

    , depression, gender, the Val66Met polymorphism, and the interaction between Val66Met and gender were identified as significant determinants of the serum BDNF level. In conclusion, our data demonstrate that other factors than a diagnosis of depression influence the serum BDNF level and the importance...

  12. Influence of XRCC1 Genetic Polymorphisms on Ionizing Radiation-Induced DNA Damage and Repair

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    Silvia Sterpone

    2010-01-01

    Full Text Available It is well known that ionizing radiation (IR can damage DNA through a direct action, producing single- and double-strand breaks on DNA double helix, as well as an indirect effect by generating oxygen reactive species in the cells. Mammals have evolved several and distinct DNA repair pathways in order to maintain genomic stability and avoid tumour cell transformation. This review reports important data showing a huge interindividual variability on sensitivity to IR and in susceptibility to developing cancer; this variability is principally represented by genetic polymorphisms, that is, DNA repair gene polymorphisms. In particular we have focussed on single nucleotide polymorphisms (SNPs of XRCC1, a gene that encodes for a scaffold protein involved basically in Base Excision Repair (BER. In this paper we have reported and presented recent studies that show an influence of XRCC1 variants on DNA repair capacity and susceptibility to breast cancer.

  13. Influence of XRCC1 Genetic Polymorphisms on Ionizing Radiation-Induced DNA Damage and Repair.

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    Sterpone, Silvia; Cozzi, Renata

    2010-07-25

    It is well known that ionizing radiation (IR) can damage DNA through a direct action, producing single- and double-strand breaks on DNA double helix, as well as an indirect effect by generating oxygen reactive species in the cells. Mammals have evolved several and distinct DNA repair pathways in order to maintain genomic stability and avoid tumour cell transformation. This review reports important data showing a huge interindividual variability on sensitivity to IR and in susceptibility to developing cancer; this variability is principally represented by genetic polymorphisms, that is, DNA repair gene polymorphisms. In particular we have focussed on single nucleotide polymorphisms (SNPs) of XRCC1, a gene that encodes for a scaffold protein involved basically in Base Excision Repair (BER). In this paper we have reported and presented recent studies that show an influence of XRCC1 variants on DNA repair capacity and susceptibility to breast cancer.

  14. Influence of ghrelin gene polymorphisms on hypertension and atherosclerotic disease.

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    Berthold, Heiner K; Giannakidou, Eleni; Krone, Wilhelm; Trégouët, David-Alexandre; Gouni-Berthold, Ioanna

    2010-02-01

    Ghrelin is involved in several metabolic and cardiovascular processes. Recent evidence suggests its involvement in blood pressure regulation and hypertension. The aim of the study was to determine associations of single-nucleotide polymorphisms (SNPs) and haplotypes of the ghrelin gene (GHRL) with hypertension and atherosclerotic disease. Six GHRL SNPs (rs27647, rs26802, rs34911341, rs696217, rs4684677 and a -473G/A (with no assigned rsID)) were investigated in a sample of 1143 hypertensive subjects and 1489 controls of Caucasian origin. Both single-locus and haplotype association analyses were performed. In single-locus analyses, only the non-synonymous rs34911341 was associated with hypertension (odds ratio (OR)=1.95 (95% confidence interval (CI): 1.26-3.02), P=0.003). Six common haplotypes with frequency >1% were inferred from the studied GHRL SNPs, and their frequency distribution was significantly different between hypertensive subjects and controls (chi(2)=12.96 with 5 d.f. (degree of freedom), P=0.024). The effect of rs26802 was found to be significantly (P=0.017) modulated by other GHRL SNPs, as its C allele conferred either an increased risk (OR=1.30 (1.08-1.57), P=0.005) or a decreased risk (OR=0.50 (0.23-1.06), P=0.07) of hypertension according to the two different haplotypes on which it can be found. No association of GHRL SNPs or haplotypes with atherosclerotic disease was observed. In conclusion, we observed statistical evidence for association between GHRL SNPs and risk of hypertension.

  15. Common Genetic Polymorphisms Influence Blood Biomarker Measurements in COPD

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    Drummond, M. Bradley; Hawkins, Gregory A.; Yang, Jenny; Chen, Ting-huei; Quibrera, Pedro Miguel; Anderson, Wayne; Barr, R. Graham; Bleecker, Eugene R.; Beaty, Terri; Casaburi, Richard; Castaldi, Peter; Cho, Michael H.; Comellas, Alejandro; Crapo, James D.; Criner, Gerard; Demeo, Dawn; Christenson, Stephanie A.; Couper, David J.; Doerschuk, Claire M.; Freeman, Christine M.; Gouskova, Natalia A.; Han, MeiLan K.; Hanania, Nicola A.; Hansel, Nadia N.; Hersh, Craig P.; Hoffman, Eric A.; Kaner, Robert J.; Kanner, Richard E.; Kleerup, Eric C.; Lutz, Sharon; Martinez, Fernando J.; Meyers, Deborah A.; Peters, Stephen P.; Regan, Elizabeth A.; Rennard, Stephen I.; Scholand, Mary Beth; Silverman, Edwin K.; Woodruff, Prescott G.; O’Neal, Wanda K.; Bowler, Russell P.

    2016-01-01

    Implementing precision medicine for complex diseases such as chronic obstructive lung disease (COPD) will require extensive use of biomarkers and an in-depth understanding of how genetic, epigenetic, and environmental variations contribute to phenotypic diversity and disease progression. A meta-analysis from two large cohorts of current and former smokers with and without COPD [SPIROMICS (N = 750); COPDGene (N = 590)] was used to identify single nucleotide polymorphisms (SNPs) associated with measurement of 88 blood proteins (protein quantitative trait loci; pQTLs). PQTLs consistently replicated between the two cohorts. Features of pQTLs were compared to previously reported expression QTLs (eQTLs). Inference of causal relations of pQTL genotypes, biomarker measurements, and four clinical COPD phenotypes (airflow obstruction, emphysema, exacerbation history, and chronic bronchitis) were explored using conditional independence tests. We identified 527 highly significant (p 10% of measured variation in 13 protein biomarkers, with a single SNP (rs7041; p = 10−392) explaining 71%-75% of the measured variation in vitamin D binding protein (gene = GC). Some of these pQTLs [e.g., pQTLs for VDBP, sRAGE (gene = AGER), surfactant protein D (gene = SFTPD), and TNFRSF10C] have been previously associated with COPD phenotypes. Most pQTLs were local (cis), but distant (trans) pQTL SNPs in the ABO blood group locus were the top pQTL SNPs for five proteins. The inclusion of pQTL SNPs improved the clinical predictive value for the established association of sRAGE and emphysema, and the explanation of variance (R2) for emphysema improved from 0.3 to 0.4 when the pQTL SNP was included in the model along with clinical covariates. Causal modeling provided insight into specific pQTL-disease relationships for airflow obstruction and emphysema. In conclusion, given the frequency of highly significant local pQTLs, the large amount of variance potentially explained by pQTL, and the

  16. Common Genetic Polymorphisms Influence Blood Biomarker Measurements in COPD.

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    Wei Sun

    2016-08-01

    Full Text Available Implementing precision medicine for complex diseases such as chronic obstructive lung disease (COPD will require extensive use of biomarkers and an in-depth understanding of how genetic, epigenetic, and environmental variations contribute to phenotypic diversity and disease progression. A meta-analysis from two large cohorts of current and former smokers with and without COPD [SPIROMICS (N = 750; COPDGene (N = 590] was used to identify single nucleotide polymorphisms (SNPs associated with measurement of 88 blood proteins (protein quantitative trait loci; pQTLs. PQTLs consistently replicated between the two cohorts. Features of pQTLs were compared to previously reported expression QTLs (eQTLs. Inference of causal relations of pQTL genotypes, biomarker measurements, and four clinical COPD phenotypes (airflow obstruction, emphysema, exacerbation history, and chronic bronchitis were explored using conditional independence tests. We identified 527 highly significant (p 10% of measured variation in 13 protein biomarkers, with a single SNP (rs7041; p = 10-392 explaining 71%-75% of the measured variation in vitamin D binding protein (gene = GC. Some of these pQTLs [e.g., pQTLs for VDBP, sRAGE (gene = AGER, surfactant protein D (gene = SFTPD, and TNFRSF10C] have been previously associated with COPD phenotypes. Most pQTLs were local (cis, but distant (trans pQTL SNPs in the ABO blood group locus were the top pQTL SNPs for five proteins. The inclusion of pQTL SNPs improved the clinical predictive value for the established association of sRAGE and emphysema, and the explanation of variance (R2 for emphysema improved from 0.3 to 0.4 when the pQTL SNP was included in the model along with clinical covariates. Causal modeling provided insight into specific pQTL-disease relationships for airflow obstruction and emphysema. In conclusion, given the frequency of highly significant local pQTLs, the large amount of variance potentially explained by pQTL, and the

  17. Influence of STAT4 polymorphism in primary Sjögren's syndrome.

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    Palomino-Morales, Rogelio J; Diaz-Gallo, Lina-Marcela; Witte, Torsten; Anaya, Juan-Manuel; Martín, Javier

    2010-05-01

    To examine the influence of STAT4 rs7574865 gene polymorphism on patients with primary Sjögren's syndrome (SS). Two different cohorts were studied: 69 patients with primary SS and 296 controls from Colombia and 108 patients with primary SS and 227 controls from Germany. Samples were genotyped for the STAT4 rs7574865 single-nucleotide polymorphism with a predesigned TaqMan single-nucleotide polymorphism genotyping assay. We carried out a metaanalysis of our results combined with data published to date. Although no significant differences were observed in the allele frequencies of STAT4 rs7574865 gene polymorphism between patients and controls in Colombians (p = 0.28, OR 1.24, 95% CI 0.82-1.87) and Germans (p = 0.08, OR 1.40, 95% CI 0.96-2.02), the metaanalysis disclosed a significant effect of the T allele on disease (p = 4.7 x 10(-6), OR 1.40, 95% CI 1.21-1.62). These data reinforce the influence of STAT4 gene on primary SS and as a general autoimmune gene.

  18. 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.

  19. The influence of the polymorphism in apolipoprotein B codon 2488 on insulin and lipid levels in a Danish twin population

    DEFF Research Database (Denmark)

    Bentzen, J; Poulsen, P; Vaag, A

    2002-01-01

    on parameters associated with the insulin resistance syndrome in Danish twins. METHODS: The effect of the polymorphism on lipid, glucose and insulin measures was studied in 548 same sex twins aged 55-74 years. RESULTS: The codon 2488 polymorphism influenced fasting triglyceride levels, as well as insulin......, as measured at 120 min in an oral glucose tolerance test. Subjects with the genotype T2488T had 14% higher triglyceride levels (P = 0.02) and 31% higher insulin levels (P = 0.004) than subjects with genotype C2488C. In twins discordant for genotype, the T-allele was associated with higher levels......AIMS: The apolipoprotein B codon 2488 polymorphism has been associated with the metabolism of lipoproteins in subjects with Type 2 diabetes. However, no data are available on the influence of the polymorphism on insulin or glucose metabolism. This study examines the impact of the polymorphism...

  20. CYP2D6 polymorphisms and their influence on risperidone treatment

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    Puangpetch A

    2016-12-01

    Full Text Available Apichaya Puangpetch,1 Natchaya Vanwong,1 Nopphadol Nuntamool,2 Yaowaluck Hongkaew,1 Monpat Chamnanphon,1 Chonlaphat Sukasem1 1Division of Pharmacogenomics and Personalized Medicine, Department of Pathology, Faculty of Medicine Ramathibodi Hospital, 2Molecular Medicine, Faculty of Science, Mahidol University, Bangkok, Thailand Abstract: Cytochrome P450 enzyme especially CYP2D6 plays a major role in biotransformation. The interindividual variations of treatment response and toxicity are influenced by the polymorphisms of this enzyme. This review emphasizes the effect of CYP2D6 polymorphisms in risperidone treatment in terms of basic knowledge, pharmacogenetics, effectiveness, adverse events, and clinical practice. Although the previous studies showed different results, the effective responses in risperidone treatment depend on the CYP2D6 polymorphisms. Several studies suggested that CYP2D6 polymorphisms were associated with plasma concentration of risperidone, 9-hydroxyrisperidone, and active moiety but did not impact on clinical outcomes. In addition, CYP2D6 poor metabolizer showed more serious adverse events such as weight gain and prolactin than other predicted phenotype groups. The knowledge of pharmacogenomics of CYP2D6 in risperidone treatment is increasing, and it can be used for the development of personalized medication in term of genetic-based dose recommendation. Moreover, the effects of many factors in risperidone treatment are still being investigated. Both the CYP2D6 genotyping and therapeutic drug monitoring are the important steps to complement the genetic-based risperidone treatment. Keywords: CYP2D6, risperidone, polymorphisms, adverse drug reaction, pharmacogenetics, pharmacokinetics, pharmacodynamics

  1. [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.

  2. Platelet receptor polymorphisms do not influence Staphylococcus aureus–platelet interactions or infective endocarditis

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    Daga, Shruti; Shepherd, James G.; Callaghan, J. Garreth S.; Hung, Rachel K.Y.; Dawson, Dana K.; Padfield, Gareth J.; Hey, Shi Y.; Cartwright, Robyn A.; Newby, David E.; Fitzgerald, J. Ross

    2011-01-01

    Cardiac vegetations result from bacterium–platelet adherence, activation and aggregation, and are associated with increased morbidity and mortality in infective endocarditis. The GPIIb/IIIa and FcγRIIa platelet receptors play a central role in platelet adhesion, activation and aggregation induced by endocarditis pathogens such as Staphylococcus aureus, but the influence of known polymorphisms of these receptors on the pathogenesis of infective endocarditis is unknown. We determined the GPIIIa platelet antigen PlA1/A2 and FcγRIIa H131R genotype of healthy volunteers (n = 160) and patients with infective endocarditis (n = 40), and investigated the influence of these polymorphisms on clinical outcome in infective endocarditis and S. aureus–platelet interactions in vitro. Platelet receptor genotype did not correlate with development of infective endocarditis, vegetation characteristics on echocardiogram or the composite clinical end-point of embolism, heart failure, need for surgery or mortality (P > 0.05 for all), even though patients with the GPIIIa PlA1/A1 genotype had increased in vivo platelet activation (P = 0.001). Furthermore, neither GPIIIa PlA1/A2 nor FcγRIIa H131R genotype influenced S. aureus-induced platelet adhesion, activation or aggregation in vitro (P > 0.05). Taken together, our data suggest that the GPIIIa and FcγRIIa platelet receptor polymorphisms do not influence S. aureus–platelet interactions in vitro or the clinical course of infective endocarditis. PMID:21044892

  3. BDNF Val66Met Polymorphism Influences Visuomotor Associative Learning and the Sensitivity to Action Observation

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    Taschereau-Dumouchel, Vincent; Hétu, Sébastien; Michon, Pierre-Emmanuel; Vachon-Presseau, Etienne; Massicotte, Elsa; De Beaumont, Louis; Fecteau, Shirley; Poirier, Judes; Mercier, Catherine; Chagnon, Yvon C.; Jackson, Philip L.

    2016-01-01

    Motor representations in the human mirror neuron system are tuned to respond to specific observed actions. This ability is widely believed to be influenced by genetic factors, but no study has reported a genetic variant affecting this system so far. One possibility is that genetic variants might interact with visuomotor associative learning to configure the system to respond to novel observed actions. In this perspective, we conducted a candidate gene study on the Brain-derived neurotrophic factor (BDNF) Val66Met polymorphism, a genetic variant linked to motor learning in regions of the mirror neuron system, and tested the effect of this polymorphism on motor facilitation and visuomotor associative learning. In a single-pulse TMS study carried on 16 Met (Val/Met and Met/Met) and 16 Val/Val participants selected from a large pool of healthy volunteers, Met participants showed significantly less muscle-specific corticospinal sensitivity during action observation, as well as reduced visuomotor associative learning, compared to Val homozygotes. These results are the first evidence of a genetic variant tuning sensitivity to action observation and bring to light the importance of considering the intricate relation between genetics and associative learning in order to further understand the origin and function of the human mirror neuron system. PMID:27703276

  4. The influence of CYP3A5 polymorphisms on haloperidol treatment in patients with alcohol addiction

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    Zastrozhin MS

    2017-12-01

    Full Text Available Mikhail Sergeevich Zastrozhin,1,2 Elena Anatolievna Grishina,1 Kristina Anatolievna Ryzhikova,1 Valery Valerievich Smirnov,3 Ludmila Mikhailovna Savchenko,1 Evgeny Alekseevich Bryun,1,2 Dmitry Alekseevich Sychev1 1Russian Medical Academy of Continuous Professional Education, Ministry of Health of the Russian Federation, 2Moscow Research and Practical Centre on Addictions, Moscow Department of Healthcare, 3National Research Center Institute of Immunology, Federal Medical-Biological Agency, Moscow, Russia Background: Isoenzymes CYP2D6 and CYP3A4, the activity of which varies widely, are involved in metabolism of haloperidol and may influence its profile of efficacy and safety.Objective: The primary aim of this study was to estimate the relationship between CYP3A5 gene polymorphism, activity of the CYP3A isoenzyme, and the risk of development of adverse drug reactions by haloperidol in patients with alcohol abuse.Methods: Sixty-six male alcohol-addicted patients participated in the study. The safety of haloperidol was evaluated by Udvalg for Kliniske Undersogelser Side Effect Rating Scale (UKU and Simpson–Angus Scale for extrapyramidal symptoms (SAS. The activity of CYP3A was evaluated by determining the concentrations of an endogenous substrate of this isoenzyme (cortisol and its urinary metabolite (6-beta-hydroxycortisol, 6-B-HC. Genotyping of CYP3A5*3 was performed by real-time polymerase chain reaction with allele-specific hybridization.Results: The frequency of A-allele occurrence in Russian population was very poor (2.27%. CYP3A5*3 polymorphism had no influence on safety profile indicators of haloperidol (UKU scale: p=0.55, SAS scale: p=0.64. In addition, there was no statistical significant difference between the values of indexes of the metabolic ratio (6-B-HC/cortisol in groups with different genotypes of CYP3A5*3: GG 5.00 (3.36; 6.39 vs AG 5.26 (2.10; 6.78 (p=0.902.Conclusion: The frequency of A-allele occurrence of CYP3A5*3 in Russian

  5. 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.

  6. Renal albumin excretion: twin studies identify influences of heredity, environment, and adrenergic pathway polymorphism

    DEFF Research Database (Denmark)

    Rao, Fangwen; Wessel, Jennifer; Wen, Gen

    2007-01-01

    biosynthesis (tyrosine hydroxylase), catabolism (monoamine oxidase A), storage/release (chromogranin A), receptor target (dopamine D1 receptor), and postreceptor signal transduction (sorting nexin 13 and rho kinase). Epistasis (gene-by-gene interaction) occurred between alleles at rho kinase, tyrosine...... hydroxylase, chromogranin A, and sorting nexin 13. Dopamine D1 receptor polymorphism showed pleiotropic effects on both albumin and dopamine excretion. These studies establish new roles for heredity and environment in albumin excretion. Urinary excretions of albumin and catecholamines are highly heritable......, and their parallel suggests adrenergic mediation of early glomerular permeability alterations. Albumin excretion is influenced by multiple adrenergic pathway genes and is, thus, polygenic. Such functional links between adrenergic activity and glomerular injury suggest novel approaches to its prediction, prevention...

  7. Quantitative assessment of the influence of tumor necrosis factor alpha polymorphism with gastritis and gastric cancer risk.

    Science.gov (United States)

    Li, Ming; Wang, Yinping; Gu, Yahong

    2014-02-01

    Tumor necrosis factor alpha (TNFA) is an important molecule in inflammatory, infectious, and tumoral processes. Inflammation is one of the early phases in the development of gastric cancer (GC). Therefore, several studies have examined the association of polymorphism in TNFA with gastritis and GC risk. A functional polymorphism, -308G>A (rs1800629), which is located in the promoter of TNFA gene, has been suggested to alter the production of TNF-α and influence cancer risk. To date, a number of studies have been carried out to investigate the relationship between the polymorphism and gastritis or GC susceptibility, but the results were conflicting. To investigate this inconsistency, we performed a meta-analysis of 36 studies for TNFA -308G>A polymorphism to evaluate the effect of TNFA on genetic susceptibility for gastritis and GC. An overall random-effects per-allele odds ratio of 1.16 (95 % confidence interval 1.04-1.29, P = 0.008) was found for the polymorphism. Significant results were also observed using dominant or recessive genetic models. In the subgroup analyses by ethnicity, significant results were found in Caucasians, whereas no significant associations were found among East Asians and other ethnic populations. No associations between the polymorphism and gastritis were observed. In addition, our data indicate that TNFA is involved in GC susceptibility and confers its effect primarily in diffuse type of tumors. Besides, -308G>A polymorphism was found to be significantly associated with both cardiac and noncardiac tumors. This meta-analysis demonstrated that the TNFA -308G>A polymorphism is a risk factor for developing GC, but the associations vary in different ethnic populations.

  8. 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.

  9. Liver fat reduction with niacin is influenced by DGAT-2 polymorphisms in hypertriglyceridemic patients.

    Science.gov (United States)

    Hu, Miao; Chu, Winnie Chiu Wing; Yamashita, Shizuya; Yeung, David Ka Wai; Shi, Lin; Wang, Defeng; Masuda, Daisaku; Yang, Yaling; Tomlinson, Brian

    2012-04-01

    Niacin reduces plasma triglycerides, but it may increase free fatty acids and insulin resistance during long-term treatment. We examined the effect of extended-release niacin on liver fat content in Chinese patients with dyslipidemia and whether the common diacylglycerol acyltransferase-2 (DGAT2) polymorphisms influenced this effect. The 39 patients (baseline liver fat content: 12.8 ± 7.6%, triglycerides: 3.30 ± 1.67 mmol/l) were treated with niacin, gradually increasing the dose to 2 g/day for a total of 23 weeks. The liver fat content and visceral/subcutaneous fat was measured before and after treatment. Subjects were genotyped for the DGAT2 rs3060 and rs101899116 polymorphisms. There were significant (P < 0.001) reductions in plasma triglycerides (-34.9 ± 37.6%), liver fat content (-47.2 ± 32.8%), and visceral fat (-6.3 ± 15.8%, P < 0.05) after niacin treatment. Mean body weight decreased by 1.46 ± 2.7% (1.17 ± 2.44 kg, P < 0.001) during the study, but liver fat changes remained significant after adjustment for age, gender, and body weight changes [mean absolute change (95% CI): -6.1% (-8.0, -4.3), P < 0.001]. The DGAT2 variant alleles were associated with a smaller reduction in liver fat content in response to niacin after adjustment for other covariates (P < 0.01). These findings suggest that niacin treatment may reduce liver fat content in Chinese patients with dyslipidemia and that the mechanism may involve inhibition of DGAT2. However, the findings might have been confounded by the small but significant reductions in body weight during the study. Future large randomized controlled trials are needed to verify these findings.

  10. HFE p.H63D polymorphism does not influence ALS phenotype and survival.

    Science.gov (United States)

    Chiò, Adriano; Mora, Gabriele; Sabatelli, Mario; Caponnetto, Claudia; Lunetta, Christian; Traynor, Bryan J; Johnson, Janel O; Nalls, Mike A; Calvo, Andrea; Moglia, Cristina; Borghero, Giuseppe; Monsurrò, Maria Rosaria; La Bella, Vincenzo; Volanti, Paolo; Simone, Isabella; Salvi, Fabrizio; Logullo, Francesco O; Nilo, Riva; Giannini, Fabio; Mandrioli, Jessica; Tanel, Raffaella; Murru, Maria Rita; Mandich, Paola; Zollino, Marcella; Conforti, Francesca L; Penco, Silvana; Brunetti, Maura; Barberis, Marco; Restagno, Gabriella

    2015-10-01

    It has been recently reported that the p.His63Asp polymorphism of the HFE gene accelerates disease progression both in the SOD1 transgenic mouse and in amyotrophic lateral sclerosis (ALS) patients. We have evaluated the effect of HFE p.His63Asp polymorphism on the phenotype in 1351 Italian ALS patients (232 of Sardinian ancestry). Patients were genotyped for the HFE p.His63Asp polymorphism (CC, GC, and GG). All patients were also assessed for C9ORF72, TARDBP, SOD1, and FUS mutations. Of the 1351 ALS patients, 363 (29.2%) were heterozygous (GC) for the p.His63Asp polymorphism and 30 (2.2%) were homozygous for the minor allele (GG). Patients with CC, GC, and GG polymorphisms did not significantly differ by age at onset, site of onset of symptoms, and survival; however, in SOD1 patients with CG or GG polymorphism had a significantly longer survival than those with a CC polymorphism. Differently from what observed in the mouse model of ALS, the HFE p.His63Asp polymorphism has no effect on ALS phenotype in this large series of Italian ALS patients. Copyright © 2015 Elsevier Inc. All rights reserved.

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

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    Erculj Nina

    2014-09-01

    Full Text Available 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.

  12. LRP5 coding polymorphisms influence the variation of peak bone mass in a normal population of French-Canadian women.

    Science.gov (United States)

    Giroux, Sylvie; Elfassihi, Latifa; Cardinal, Guy; Laflamme, Nathalie; Rousseau, François

    2007-05-01

    Bone mineral density has a strong genetic component but it is also influenced by environmental factors making it a complex trait to study. LRP5 gene was previously shown to be involved in rare diseases affecting bone mass. Mutations associated with gain-of-function were described as well as loss-of-function mutations. Following this discovery, many frequent LRP5 polymorphisms were tested against the variation of BMD in the normal population. Heel bone parameters (SOS, BUA) were measured by right calcaneal QUS in 5021 healthy French-Canadian women and for 2104 women, BMD evaluated by DXA at two sites was available (femoral neck (FN) and lumbar spine (LS)). Among women with QUS measures and those with DXA measures, 26.5% and 32.8% respectively were premenopausal, 9.2% and 10.7% were perimenopausal and 64.2% and 56.5% were postmenopausal. About a third of the peri- and postmenopausal women never received hormone therapy. Two single nucleotide coding polymorphisms (Val667Met and Ala1330Val) in LRP5 gene were genotyped by allele-specific PCR. All bone measures were tested individually for associations with each polymorphism by analysis of covariance with adjustment for non genetic risk factors. Furthermore, haplotype analysis was performed to take into account the strong linkage disequilibrium between the two polymorphisms. The two LRP5 polymorphisms were found to be associated with all five bone measures (L2L4 and femoral neck DXA as well as heel SOS, BUA and stiffness index) in the whole sample. Premenopausal women drove the association as expected from the proposed role of LRP5 in peak bone mass. Our results suggest that the Val667Met polymorphism is the causative variant but this remains to be functionally proven.

  13. Cytokine Polymorphisms, Their Influence and Levels in Brazilian Patients with Pulmonary Tuberculosis during Antituberculosis Treatment

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    Eliana Peresi

    2013-01-01

    Full Text Available Cytokines play an essential role during active tuberculosis disease and cytokine genes have been described in association with altered cytokine levels. Therefore, the aim of this study was to verify if IFNG, IL12B, TNF, IL17A, IL10, and TGFB1 gene polymorphisms influence the immune response of Brazilian patients with pulmonary tuberculosis (PTB at different time points of antituberculosis treatment (T1, T2, and T3. Our results showed the following associations: IFNG +874 T allele and IFNG +2109 A allele with higher IFN-γ levels; IL12B +1188 C allele with higher IL-12 levels; TNF −308 A allele with higher TNF-α plasma levels in controls and mRNA levels in PTB patients at T1; IL17A A allele at rs7747909 with higher IL-17 levels; IL10 −819 T allele with higher IL-10 levels; and TGFB1 +29 CC genotype higher TGF-β plasma levels in PTB patients at T2. The present study suggests that IFNG +874T/A, IFNG +2109A/G, IL12B +1188A/C, IL10 −819C/T, and TGFB1 +21C/T are associated with differential cytokine levels in pulmonary tuberculosis patients and may play a role in the initiation and maintenance of acquired cellular immunity to tuberculosis and in the outcome of the active disease while on antituberculosis treatment.

  14. Genetic influences on insight problem solving: the role of catechol-O-methyltransferase (COMT) gene polymorphisms.

    Science.gov (United States)

    Jiang, Weili; Shang, Siyuan; Su, Yanjie

    2015-01-01

    People may experience an "aha" moment, when suddenly realizing a solution of a puzzling problem. This experience is called insight problem solving. Several findings suggest that catecholamine-related genes may contribute to insight problem solving, among which the catechol-O-methyltransferase (COMT) gene is the most promising candidate. The current study examined 753 healthy individuals to determine the associations between 7 candidate single nucleotide polymorphisms on the COMT gene and insight problem-solving performance, while considering gender differences. The results showed that individuals carrying A allele of rs4680 or T allele of rs4633 scored significantly higher on insight problem-solving tasks, and the COMT gene rs5993883 combined with gender interacted with correct solutions of insight problems, specifically showing that this gene only influenced insight problem-solving performance in males. This study presents the first investigation of the genetic impact on insight problem solving and provides evidence that highlights the role that the COMT gene plays in insight problem solving.

  15. Progranulin genetic polymorphisms influence progression of disability and relapse recovery in multiple sclerosis.

    Science.gov (United States)

    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.

  16. Polymorphisms at Amino Acid Residues 141 and 154 Influence Conformational Variation in Ovine PrP

    Science.gov (United States)

    Yang, Sujeong; Thackray, Alana M.; Hopkins, Lee; Monie, Tom P.; Burke, David F.; Bujdoso, Raymond

    2014-01-01

    Polymorphisms in ovine PrP at amino acid residues 141 and 154 are associated with susceptibility to ovine prion disease: Leu141Arg154 with classical scrapie and Phe141Arg154 and Leu141His154 with atypical scrapie. Classical scrapie is naturally transmissible between sheep, whereas this may not be the case with atypical scrapie. Critical amino acid residues will determine the range or stability of structural changes within the ovine prion protein or its functional interaction with potential cofactors, during conversion of PrPC to PrPSc in these different forms of scrapie disease. Here we computationally identified that regions of ovine PrP, including those near amino acid residues 141 and 154, displayed more conservation than expected based on local structural environment. Molecular dynamics simulations showed these conserved regions of ovine PrP displayed genotypic differences in conformational repertoire and amino acid side-chain interactions. Significantly, Leu141Arg154 PrP adopted an extended beta sheet arrangement in the N-terminal palindromic region more frequently than the Phe141Arg154 and Leu141His154 variants. We supported these computational observations experimentally using circular dichroism spectroscopy and immunobiochemical studies on ovine recombinant PrP. Collectively, our observations show amino acid residues 141 and 154 influence secondary structure and conformational change in ovine PrP that may correlate with different forms of scrapie. PMID:25126555

  17. The Influence of Single Nucleotide Polymorphism Microarray-Based Molecular Karyotype on Preimplantation Embryonic Development Potential.

    Directory of Open Access Journals (Sweden)

    Gang Li

    Full Text Available In order to investigate the influence of the molecular karyotype based on single nucleotide polymorphism (SNP microarray on embryonic development potential in preimplantation genetic diagnosis (PGD, we retrospectively analyzed the clinical data generated by PGD using embryos retrieved from parents with chromosome rearrangements in our center. In total, 929 embryos from 119 couples had exact diagnosis and development status. The blastocyst formation rate of balanced molecular karyotype embryos was 56.6% (276/488, which was significantly higher than that of genetic imbalanced embryos 24.5% (108/441 (P35 respectively. Blastocyst formation rates of male and female embryos were 44.5% (183/411 and 38.8% (201/518 respectively, with no significant difference between them (P>0.05. The rates of balanced molecular karyotype embryos vary from groups of embryos with different cell numbers at 68 hours after insemination. The blastocyst formation rate of embryos with 6-8 cells (48.1% was significantly higher than that of embryos with 8 cells (42.9% (P8 cells, embryos with 6-8 blastomeres have higher rate of balanced molecular karyotype and blastocyst formation.

  18. Sex determines the influence of smoking and gene polymorphism on glutathione peroxidase activity in erythrocytes

    DEFF Research Database (Denmark)

    Malling, Tine Halsen; Sigsgaard, Torben; Andersen, Helle Raun

    2009-01-01

    OBJECTIVE: Glutathione peroxidase 1 (GPX1) is one of the major oxidative enzymes. Our aim was to characterize factors influencing its activity and to determine whether or not the activity is associated with asthma. MATERIAL AND METHODS: Serum selenium concentration was measured, GPX1 polymorphisms...... %) had doctor-diagnosed asthma. RESULTS: The average serum selenium concentration was too low for optimal enzyme activity (mean (SE), 83.4 (0.76) ng/mL). GPX1 activity in men was lower than in women, 52.6 (0.66) and 56.4 (0.59) U/g protein, respectively (p... associated with serum selenium concentration (p = 0.005) and negatively associated with both active smoking (p = 0.009) and exposure to environmental tobacco smoke (p = 0.02). In women, activity was associated with genotypes with 59.2 (1.4), 56.0 (1.4) and 54.2 (1.4) U/g protein in the homozygote wild...

  19. Polymorphisms in xenobiotic metabolizing enzymes and diet influence colorectal adenoma risk.

    Science.gov (United States)

    Northwood, Emma L; Elliott, Faye; Forman, David; Barrett, Jennifer H; Wilkie, Murray J V; Carey, Francis A; Steele, Robert J C; Wolf, Roland; Bishop, Timothy; Smith, Gillian

    2010-05-01

    We have earlier shown that diet and xenobiotic metabolizing enzyme genotypes influence colorectal cancer risk, and now investigate whether similar associations are seen in patients with premalignant colorectal adenomas (CRA), recruited during the pilot phase of the Scottish Bowel Screening Programme. Nineteen polymorphisms in 13 genes [cytochrome P450 (P450), glutathione S-transferase (GST), N-acetyl transferase, quinone reductase (NQ01) and microsomal epoxide hydrolase (EPHX1) genes] were genotyped using multiplex PCR or Taqman-based allelic discrimination assays and analyzed in conjunction with diet, assessed by food frequency questionnaire, in a case-control study [317 CRA cases (308 cases genotyped), 296 controls]. Findings significant at a nominal 5% level are reported. CRA risk was inversely associated with fruit (P=0.02, test for trend) and vegetable (P=0.001, test for trend) consumption. P450 CYP2C9*3 heterozygotes had reduced CRA risk compared with homozygotes for the reference allele [odds ratio (OR): 0.60; 95% confidence interval (CI): 0.36-0.99], whereas CYP2D6*4 homozygotes (OR: 2.72; 95% CI: 1.18-6.27) and GSTM1 'null' individuals (OR: 1.43; 95% CI: 1.04-1.98) were at increased risk. The protective effect of fruit consumption was confined to GSTP1 (Ala114Val) reference allele homozygotes (OR: 0.49; 95% CI: 0.34-0.71, P=0.03 for interaction). CRA risk was not associated with meat consumption, although a significant interaction between red meat consumption and EPHX1 (His139Arg) genotype was noted (P=0.02 for interaction). We report the novel associations between P450 genotype and CRA risk, and highlight the risk association with GSTM1 genotype, common to our CRA and cancer case-control series. In addition, we report a novel modifying influence of GSTP1 genotype on dietary chemoprevention. These novel findings require independent confirmation.

  20. Both COMT Val158Met single nucleotide polymorphism and sex-dependent differences influence response inhibition

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    Valentina eMione

    2015-05-01

    Full Text Available Reactive and proactive control of actions are cognitive abilities that allow to deal with a continuously changing environment by adjusting already programmed actions. They also set forthcoming acts by evaluating the outcome of the previous ones. Earlier studies highlighted sex related differences in the strategies and in the pattern of brain activation during cognitive tasks involving reactive and proactive control. To further identify sex-dependent characteristics in the cognitive control of actions, in this study we have assessed whether/how differences in reactive and proactive control were modulated by the COMT Val158Met single nucleotide polymorphism, a genetic factor known to influence the functionality of the dopaminergic system, in particular at the level of prefrontal cortex. Two groups of male and female participants were further sorted according to their genotype (Val/Met, Val/Val and Met/Met and tested in a stop signal task, a consolidated tool to measure reactive and proactive control in experimental and clinical settings. In each group of participants we estimated both a measure of the capacity to react to unexpected events and the ability of monitoring their performance. The between groups comparison of these measures indicated a poorer ability of male individuals carrying the Val/Val genotype in error-monitoring, suggesting that differences between sexes could be influenced by the efficiency of COMT and that other sex-specific factors have to be considered. The comprehension of inter-groups behavioral and physiological correlates of cognitive control will provide more accurate diagnostic tools for predicting the incidence and the development of pathologies like ADHD or deviant behaviors as drug or alcohol abuse.

  1. Influence of β(2)-adrenergic receptor polymorphisms on asthma exacerbation in children with severe asthma regularly receiving salmeterol.

    Science.gov (United States)

    Giubergia, Verónica; Gravina, Luis; Castaños, Claudio; Chertkoff, Lilien

    2013-03-01

    New evidence suggests that different β(2)-adrenergic receptor (β2AR) polymorphisms may influence asthma control in patients receiving long-acting β(2)agonists (LABAs) as regular therapy. To determine the influence of β2AR polymorphisms on asthma exacerbations in children with severe asthma from Argentina receiving inhaled corticosteroid (ICS) and LABAs regularly. Ninety-seven children with severe asthma were genotyped for polymorphisms of β2AR at codons 16 and 27. The number of severe exacerbations, the time of first asthma exacerbation, and the number of hospitalizations during 12 months were assessed. Changes on pulmonary function from the beginning to the end of the study were also evaluated. The number of overall asthma exacerbations and the proportion of children with these events were similar among β2AR genotypes at position 16 (Arg/Arg, Arg/Gly, and Gly/Gly) and at position 27 (Gln/Gln, Gln/Glu, and Glu/Glu). The time to first asthma exacerbation was similar among individuals carrying different β2AR polymorphisms. No β2AR genotype association was found in relation to the number of hospitalizations. Longitudinal analysis of forced expiratory volume in 1 second from baseline to the end of the study also showed no differences among β2AR genotypes at position 16 or 27. No association was observed among the 3 most common haplotypes (Arg/Arg-Gln/Gln, Gly/Gly-Gln/Gln, and Gly/Gly-Glu/Glu) and the number of participants with asthmatic crisis or with the overall number of exacerbations. β2AR polymorphisms were not associated with an increased risk of having asthma exacerbations or lung function decline in a population of Argentinian children with severe asthma receiving ICS and LABAs regularly. Copyright © 2013 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

  2. Influence of kynurenine 3-monooxygenase (KMO) gene polymorphism on cognitive function in schizophrenia✰,✰✰

    Science.gov (United States)

    Wonodi, Ikwunga; McMahon, Robert P.; Krishna, Nithin; Mitchell, Braxton D.; Liu, Judy; Glassman, Matthew; Hong, L. Elliot; Gold, James M.

    2015-01-01

    Background Cognitive deficits compromise quality of life and productivity for individuals with schizophrenia and have no effective treatments. Preclinical data point to the kynurenine pathway of tryptophan metabolism as a potential target for pro-cognitive drug development. We have previously demonstrated association of a kynurenine 3-monooxygenase (KMO) gene variant with reduced KMO gene expression in postmortem schizophrenia cortex, and neurocognitive endophenotypic deficits in a clinical sample. KMO encodes kynurenine 3-monooxygenase (KMO), the rate-limiting microglial enzyme of cortical kynurenine metabolism. Aberration of the KMO gene might be the proximal cause of impaired cortical kynurenine metabolism observed in schizophrenia. However, the relationship between KMO variation and cognitive function in schizophrenia is unknown. This study examined the effects of the KMO rs2275163C>T C (risk) allele on cognitive function in schizophrenia. Methods We examined the association of KMO polymorphisms with general neuropsychological performance and P50 gating in a sample of 150 schizophrenia and 95 healthy controls. Results Consistent with our original report, the KMO rs2275163C>T C (risk) allele was associated with deficits in general neuropsychological performance, and this effect was more marked in schizophrenia compared with controls. Additionally, the C (Arg452) allele of the missense rs1053230C>T variant (KMO Arg452Cys) showed a trend effect on cognitive function. Neither variant affected P50 gating. Conclusions These data suggest that KMO variation influences a range of cognitive domains known to predict functional outcome. Extensive molecular characterization of this gene would elucidate its role in cognitive function with implications for vertical integration with basic discovery. PMID:25464917

  3. Influence of kynurenine 3-monooxygenase (KMO) gene polymorphism on cognitive function in schizophrenia.

    Science.gov (United States)

    Wonodi, Ikwunga; McMahon, Robert P; Krishna, Nithin; Mitchell, Braxton D; Liu, Judy; Glassman, Matthew; Hong, L Elliot; Gold, James M

    2014-12-01

    Cognitive deficits compromise quality of life and productivity for individuals with schizophrenia and have no effective treatments. Preclinical data point to the kynurenine pathway of tryptophan metabolism as a potential target for pro-cognitive drug development. We have previously demonstrated association of a kynurenine 3-monooxygenase (KMO) gene variant with reduced KMO gene expression in postmortem schizophrenia cortex, and neurocognitive endophenotypic deficits in a clinical sample. KMO encodes kynurenine 3-monooxygenase (KMO), the rate-limiting microglial enzyme of cortical kynurenine metabolism. Aberration of the KMO gene might be the proximal cause of impaired cortical kynurenine metabolism observed in schizophrenia. However, the relationship between KMO variation and cognitive function in schizophrenia is unknown. This study examined the effects of the KMO rs2275163C>T C (risk) allele on cognitive function in schizophrenia. We examined the association of KMO polymorphisms with general neuropsychological performance and P50 gating in a sample of 150 schizophrenia and 95 healthy controls. Consistent with our original report, the KMO rs2275163C>T C (risk) allele was associated with deficits in general neuropsychological performance, and this effect was more marked in schizophrenia compared with controls. Additionally, the C (Arg452) allele of the missense rs1053230C>T variant (KMO Arg452Cys) showed a trend effect on cognitive function. Neither variant affected P50 gating. These data suggest that KMO variation influences a range of cognitive domains known to predict functional outcome. Extensive molecular characterization of this gene would elucidate its role in cognitive function with implications for vertical integration with basic discovery. Copyright © 2014 Elsevier B.V. All rights reserved.

  4. Genetic polymorphisms in homologous recombination repair genes in healthy Slovenian population and their influence on DNA damage

    International Nuclear Information System (INIS)

    Goricar, Katja; Erculj, Nina; Zadel, Maja; Dolzan, Vita

    2012-01-01

    Homologous recombination (HR) repair is an important mechanism involved in repairing double-strand breaks in DNA and for maintaining genomic stability. Polymorphisms in genes coding for enzymes involved in this pathway may influence the capacity for DNA repair. The aim of this study was to select tag single nucleotide polymorphisms (SNPs) in specific genes involved in HR repair, to determine their allele frequencies in a healthy Slovenian population and their influence on DNA damage detected with comet assay. In total 373 individuals were genotyped for nine tag SNPs in three genes: XRCC3 722C>T, XRCC3 -316A>G, RAD51 -98G>C, RAD51 -61G>T, RAD51 1522T>G, NBS1 553G>C, NBS1 1197A>G, NBS1 37117C>T and NBS1 3474A>C using competitive allele-specific amplification (KASPar assay). Comet assay was performed in a subgroup of 26 individuals to determine the influence of selected SNPs on DNA damage. We observed that age significantly affected genotype frequencies distribution of XRCC3 -316A>G (P = 0.039) in healthy male blood donors. XRCC3 722C>T (P = 0.005), RAD51 -61G>T (P = 0.023) and NBS1 553G>C (P = 0.008) had a statistically significant influence on DNA damage. XRCC3 722C>T, RAD51 -61G>T and NBS1 553G>C polymorphisms significantly affect the repair of damaged DNA and may be of clinical importance as they are common in Slovenian population

  5. Influence of p53 (rs1625895 polymorphism in kidney transplant recipients

    Directory of Open Access Journals (Sweden)

    Negar Azarpira

    2014-01-01

    Full Text Available Reperfusion injury predisposes the kidney allograft to acute rejection. Apoptosis is a mechanism that results in graft injury, and TP53 is an important involved gene. To determine the association between single nucleotide polymorphism (SNP in the pro-apoptotic protein p53 (rs1625895 and acute rejection in renal transplants, we studied 100 recipients of kidney allografts and 100 healthy individuals served as controls. The polymorphism was determined by the polymerase chain reaction restriction-fragment length polymorphism (PCR-RFLP test. Overall, 31 recipients developed rejection. There was no difference in the genotype frequencies between the recipients and the controls. However, we found a difference of genotype and allele frequencies between recipients with and those without rejection. The WW genotype was more frequent in recipients with rejection. Although rejection is a complex immunologic event and functional importance of SNPs has not been confirmed yet, we suggest that wild type p53 may promote apoptosis during inflammation.

  6. Influence of COMT Val158Met polymorphism on emotional decision-making: A sex-dependent relationship?

    Science.gov (United States)

    Costa, Danielle de Souza; Bechara, Antoine; de Paula, Jonas Jardim; Romano-Silva, Marco Aurélio; Correa, Humberto; Lage, Guilherme Menezes; Miranda, Débora Marques de; Malloy-Diniz, Leandro Fernandes

    2016-12-30

    The biological underpinnings of sex-related differences in decision-making are still under-explored. The COMT gene is related to sexual dimorphism and with different choices made under uncertainty, albeit no study has specifically investigated a moderation effect of sex on the association between the COMT gene and the performance on decision-making paradigms. In this study, we investigated the influence of the COMT Val 158 Met polymorphism on Iowa Gambling Task (IGT) performance depending on sex in a healthy adult sample. Participants were 192 healthy adults (84 men and 108 women). The first 40 choices in the IGT were considered decisions under ambiguity and the last 60 choices decisions under risk. To test our moderation hypothesis we used a separate regressions approach. The results revealed a sex-dependent effect of COMT Va l 158 Met polymorphism on decision-making as measured by the IGT. Val/Val women showed the best performance in the last trials of the IGT. Therefore, the COMT Val 158 Met polymorphism may be considered a genetic marker underlying sex differences in decision-making. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  7. Vasospastic angina and microvascular angina are differentially influenced by PON1 A632G polymorphism in the Japanese.

    Science.gov (United States)

    Mashiba, Junko; Koike, George; Kamiunten, Hitoshi; Ikeda, Manami; Sunagawa, Kenji

    2005-12-01

    Ethnicity and smoking are well-known risk factors for the pathogenesis of coronary vasospasm. Oxidative stress induced by smoking plays a crucial role in coronary vasospasm, but is not enough to account for the pathogenesis of coronary vasospasm, indicating that genetic factors are strongly involved. The study group comprised 162 vasospastic angina patients (VSAs), 61 microvascular angina patients (MVAs) and 61 non-responders (NRs) diagnosed by acetylcholine provocation test. Four polymorphisms of the oxidative stress related genes, cytochrome b-245, alpha polypeptide gene (CYBA) C242T and A640G, paraoxonase 1 gene (PON1) A632G, phospholipase A2 group VII gene (PLA2G7) G994T were genotyped. Allele frequency of PON1 632-G was significantly higher in both the VSA with dominant fashion and the MVA with recessive fashion compared with NR. This association was strongly influenced by gender in the MVA only. There were no significant associations between the other polymorphisms and coronary vasospasm. In addition, the allele frequency of PON1 632-G in the Japanese was higher than in Caucasians. There was a significant association between PON1 A632G polymorphism and MVA as well as VSA, but the impact of this on VSA and MVA is different in the Japanese.

  8. Influence of the OGG1 Ser326Cys polymorphism on oxidatively damaged DNA and repair activity

    DEFF Research Database (Denmark)

    Jensen, Annie Aarup; Løhr, Mille; Eriksen, Louise

    2012-01-01

    of the comet assay. We collected blood samples from 1,019 healthy subjects and genotyped for the OGG1 Ser326Cys polymorphism. We found 49 subjects homozygous for the variant genotype (Cys/Cys) and selected same numbers of age-matched subjects with the heterozygous (Ser/Cys) and homozygous wild-type genotype...

  9. Vitamin D Receptor Gene Polymorphisms Influence T1D Susceptibility among Pakistanis

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    Maryam Mukhtar

    2017-01-01

    Full Text Available Background. The vitamin D receptor (VDR gene regulates insulin secretion from the pancreas and acts as a mediator of the immune response through vitamin D. Polymorphism in VDR causes alterations in the functioning of vitamin D, leading to type 1 diabetes (T1D predisposition. The aim of the present study was to determine VDR gene polymorphism in association with T1D in Pakistanis. Methods. The association was evaluated by selecting rs2228570 (FokΙ, rs7975232 (ApaΙ, and rs731236 (TaqΙ polymorphic sites in 102 patients and 100 controls. Genotypes were identified by DNA sequencing and PCR-RFLP. Results. The allelic and genotypic frequencies of FokΙ and ApaI were significantly associated with T1D (p0.05. CCGC, CCGG, CCTC, and CCTG haplotypes were significantly associated with disease development (p<0.05. However, CTGG haplotype was protective towards T1D (p<0.01. Conclusion. VDR polymorphisms were identified as susceptible regions for T1D development in the Pakistani population.

  10. The Influence of BMX Gene Polymorphisms on Clinical Symptoms after Mild Traumatic Brain Injury

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    Yu-Jia Wang

    2014-01-01

    Full Text Available Mild traumatic brain injury (mTBI is one of the most common neurological disorders. Most patients diagnosed with mTBI could fully recover, but 15% of patients suffer from persistent symptoms. In recent studies, genetic factors were found to be associated with recovery and clinical outcomes after TBI. In addition, results from our previous research have demonstrated that the bone marrow tyrosine kinase gene in chromosome X (BMX, a member of the Tec family of kinases, is highly expressed in rats with TBI. Therefore, our aim in this study was to identify the association between genetic polymorphisms of BMX and clinical symptoms following mTBI. Four tagging single nucleotide polymorphisms (tSNPs of BMX with minimum allele frequency (MAF >1% were selected from the HapMap Han Chinese database. Among these polymorphisms, rs16979956 was found to be associated with the Beck anxiety inventory (BAI and dizziness handicap inventory (DHI scores within the first week after head injury. Additionally, another SNP, rs35697037, showed a significant correlation with dizziness symptoms. These findings suggested that polymorphisms of the BMX gene could be a potential predictor of clinical symptoms following mTBI.

  11. The influence of metabolic gene polymorphisms on urinary 1-hydroxypyrene concentration in Thai bus drivers.

    Science.gov (United States)

    Petchpoung, Krittaya; Kaojarern, Sming; Yoovathaworn, Krongtong; Sura, Thanyachai; Sirivarasai, Jintana

    2011-01-01

    Polycyclic aromatic hydrocarbons (PAHs) are associated with an increased cancer risk. CYP1A1 and GSTs enzymes are important in metabolism of PAHs. Genetic polymorphisms of these enzymes are responsible for enzyme activity and concentration variation. The objectives of this study were to evaluate association of 1-OHP concentration with genetic polymorphisms of CYP1A1 and GSTs in Thai bus drivers. The results showed that 1-OHP levels in bus drivers were significantly higher than that in the control group. Significant difference in 1-OHP was found between smokers and non-smokers, in only bus drivers. Significantly increasing of 1-OHP levels were observed in bus drivers with CYP1A1 MspI and exon 7 variants. Whereas, bus drivers with GSTP1 Val and GSTM1 null genotypes showed decreasing in excretion of 1-OHP. No association between 1-OHP and polymorphisms of GSTT1 was found. This study indicated that 1-OHP concentrations were associated with exposure to air pollution, cigarette smoking and polymorphisms of CYP1A1, GSTM1 and GSTP1 genes. Copyright © 2010 Elsevier B.V. All rights reserved.

  12. Sleep homeostatic pressure and PER3 VNTR gene polymorphism influence antidepressant response to sleep deprivation in bipolar depression.

    Science.gov (United States)

    Dallaspezia, Sara; Locatelli, Clara; Lorenzi, Cristina; Pirovano, Adele; Colombo, Cristina; Benedetti, Francesco

    2016-03-01

    Combined Total sleep deprivation (TSD) and light therapy (LT) cause a rapid improvement in bipolar depression which has been hypothesized to be paralleled by changes in sleep homeostasis. Recent studies showed that bipolar patients had lower changes of EEG theta power after sleep and responders to antidepressant TSD+LT slept less and showed a lower increase of EEG theta power then non-responders. A polymorphism in PER3 gene has been associated with diurnal preference, sleep structure and homeostatic response to sleep deprivation in healthy subjects. We hypothesized that the individual variability in the homeostatic response to TSD could be a correlate of antidepressant response and be influenced by genetic factors. We administered three TSD+LT cycles to bipolar depressed patients. Severity of depression was rated on Hamilton Depression Rating Scale. Actigraphic recordings were performed in a group of patients. PER3 polymorphism influenced changes in total sleep time (F=2.24; p=0.024): while PER3(4/4) and PER3(4/5) patients showed a reduction in it after treatment, PER3(5/5) subjects showed an increase of about 40min, suggesting a higher homeostatic pressure. The same polymorphism influenced the change of depressive symptomatology during treatment (F=3.72; p=0.028). Sleep information was recorded till the day after the end of treatment: a longer period of observation could give more information about the possible maintenance of allostatic adaptation. A higher sleep homeostatic pressure reduced the antidepressant response to TSD+LT, while an allostatic adaptation to sleep loss was associated with better response. This process seems to be under genetic control. Copyright © 2015 Elsevier B.V. All rights reserved.

  13. A Single Nucleotide Polymorphism in the Bax Gene Promoter Affects Transcription and Influences Retinal Ganglion Cell Death

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    Sheila J Semaan

    2010-03-01

    Full Text Available Pro-apoptotic Bax is essential for RGC (retinal ganglion cell death. Gene dosage experiments in mice, yielding a single wild-type Bax allele, indicated that genetic background was able to influence the cell death phenotype. DBA/2J Bax+/− mice exhibited complete resistance to nerve damage after 2 weeks (similar to Bax −/− mice, but 129B6 Bax+/− mice exhibited significant cell loss (similar to wild-type mice. The different cell death phenotype was associated with the level of Bax expression, where 129B6 neurons had twice the level of endogenous Bax mRNA and protein as DBA/2J neurons. Sequence analysis of the Bax promoters between these strains revealed a single nucleotide polymorphism (T129B6 to CDBA/2J at position −515. A 1.5- to 2.5-fold increase in transcriptional activity was observed from the 129B6 promoter in transient transfection assays in a variety of cell types, including RGC5 cells derived from rat RGCs. Since this polymorphism occurred in a p53 half-site, we investigated the requirement of p53 for the differential transcriptional activity. Differential transcriptional activity from either 129B6 or DBA/2J Bax promoters were unaffected in p53−/− cells, and addition of exogenous p53 had no further effect on this difference, thus a role for p53 was excluded. Competitive electrophoretic mobility-shift assays identified two DNA-protein complexes that interacted with the polymorphic region. Those forming Complex 1 bound with higher affinity to the 129B6 polymorphic site, suggesting that these proteins probably comprised a transcriptional activator complex. These studies implicated quantitative expression of the Bax gene as playing a possible role in neuronal susceptibility to damaging stimuli.

  14. INFLUENCE OF GENETIC POLYMORPHISM IN FABP3 AND LEPR GENES ON INTRAMUSCULAR FAT CONTENT IN PIG CARCASSES

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    Kristina Budimir

    2014-06-01

    Full Text Available Intensive production conditions, selection directed to increase the percentage of muscle tissue in carcasses and consumer demand have led to a reduction of intramuscular fat content in pig carcasses. Intramuscular fat is a factor affecting the flavor, juiciness and tenderness of pork meat. FABP protein family causes the differences in the content of intramuscular fat in different pig breeds. FABP3 and LEPR gene are candidate genes for intramuscular fat content and their polymorphisms explain the variability that can occur in different pig breeds. The aim of this paper is to demonstrate the influence of genes on different intramuscular fat content in pig carcasses due to pigs genotype.

  15. High Molecular Weight Adiponectin Levels are Neither Influenced by Adiponectin Polymorphisms Nor Associated with Insulin Resistance in Mixed-Ancestry Hyperglycemic Subjects from South Africa

    Directory of Open Access Journals (Sweden)

    Zemlin Annalise E

    2016-10-01

    Full Text Available Background: High molecular weight (HMW adiponectin has antiatherogenic, antiinflammatory and antidiabetic properties and these effects have been linked to its effect on high density lipoprotein cholesterol (HDL-c. Single nucleotide polymorphisms (SNPs in the adiponectin gene influence adiponectin levels. We examined the relationship between HMW-adiponectin levels and cardiometabolic traits in normo- and hyperglycemic mixed ancestry South Africans and correlated these levels to two common polymorphisms.

  16. Culture, distress, and oxytocin receptor polymorphism (OXTR) interact to influence emotional support seeking

    OpenAIRE

    Kim, Heejung S.; Sherman, David K.; Sasaki, Joni Y.; Xu, Jun; Chu, Thai Q.; Ryu, Chorong; Suh, Eunkook M.; Graham, Kelsey; Taylor, Shelley E.

    2010-01-01

    Research has demonstrated that certain genotypes are expressed in different forms, depending on input from the social environment. To examine sensitivity to cultural norms regarding emotional support seeking as a type of social environment, we explored the behavioral expression of oxytocin receptor polymorphism (OXTR) rs53576, a gene previously related to socio-emotional sensitivity. Seeking emotional support in times of distress is normative in American culture but not in Korean culture. Con...

  17. IDE Gene Polymorphism Influences on BPSD in Mild Dementia of Alzheimer's Type

    Directory of Open Access Journals (Sweden)

    Noriko Sato

    2008-01-01

    Full Text Available Insulin degrading enzyme (IDE degrades amyloid (A, which may inhibit the accumulation of A in a brain affected with dementia of Alzheimer's type (DAT. A decrease in the activity of IDE results in changes in glucose utilization in the brain, which could affect the cognitive and psychiatric symptoms of DAT. We investigated a possible association of IDE gene polymorphism and the behavioral and psychological symptoms of dementia (BPSD in mild DAT. The genotyping for IDE and apolipoprotein E (ApoE was determined in 207 patients with mild DAT and 215 controls. The occurrence of BPSD was demonstrated using the Behavioral Pathology in Alzheimer's Disease Rating Scale (BEHAVE-AD. IDE gene polymorphism is unlikely to play a substantial role in conferring susceptibility to DAT, but it may be involved in the development of affective disturbance through the course of mild DAT, regardless of the presence of an ApoE 4 allele. The present data could be the result of a small sample size. Further investigations using larger samples are thus required to clarify the correlation between IDE gene polymorphism, susceptibility to DAT, and emergence of BPSD.

  18. The modulatory influence of the functional COMT Val158Met polymorphism on lexical decisions and semantic priming.

    Science.gov (United States)

    Reuter, Martin; Montag, Christian; Peters, Kristina; Kocher, Anne; Kiefer, Markus

    2009-01-01

    The role of the prefrontal Cortex (PFC) in higher cognitive functions - including working memory, conflict resolution, set shifting and semantic processing - has been demonstrated unequivocally. Despite the great heterogeneity among tasks measuring these phenotypes, due in part to the different cognitive sub-processes implied and the specificity of the stimulus material used, there is agreement that all of these tasks recruit an executive control system located in the PFC. On a biochemical level it is known that the dopaminergic system plays an important role in executive control functions. Evidence comes from molecular genetics relating the functional COMT Val158Met polymorphism to working memory and set shifting. In order determine whether this pattern of findings generalises to linguistic and semantic processing, we investigated the effects of the COMT Val158Met polymorphism in lexical decision making using masked and unmasked versions of the semantic priming paradigm on N = 104 healthy subjects. Although we observed strong priming effects in all conditions (masked priming, unmasked priming with short/long stimulus asynchronies (SOAs), direct and indirect priming), COMT was not significantly related to priming, suggesting no reliable influence on semantic processing. However, COMT Val158Met was strongly associated with lexical decision latencies in all priming conditions if considered separately, explaining between 9 and 14.5% of the variance. Therefore, the findings indicate that COMT mainly influences more general executive control functions in the PFC supporting the speed of lexical decisions.

  19. The modulatory influence of the functional COMT Val158Met polymorphism on lexical decisions and semantic priming

    Directory of Open Access Journals (Sweden)

    Martin Reuter

    2009-08-01

    Full Text Available The role of the prefrontal Cortex (PFC in higher cognitive functions - including working memory, conflict resolution, set shifting and semantic processing - has been demonstrated unequivocally. Despite the great heterogeneity among tasks measuring these phenotypes, due in part to the different cognitive sub-processes implied and the specificity of the stimulus material used, there is agreement that all of these tasks recruit an executive control system located in the PFC. On a biochemical level it is known that the dopaminergic system plays an important role in executive control functions. Evidence comes from molecular genetics relating the functional COMT Val158Met polymorphism to working memory and set shifting. In order determine whether this pattern of findings generalises to linguistic and semantic processing, we investigated the effects of the COMT Val158Met polymorphism in lexical decision making using masked and unmasked versions of the semantic priming paradigm on N=104 healthy subjects. Although we observed strong priming effects in all conditions (masked priming, unmasked priming with short/long stimulus asynchronies (SOAs, direct and indirect priming, COMT was not significantly related to masked priming, suggesting no reliable influence on semantic processing. However, COMT Val158Met was strongly associated with lexical decision latencies in all priming conditions if considered separately, explaining between 9 to 14.5 % of the variance. Therefore, the findings indicate that COMT mainly influences more general executive control functions in the PFC supporting the speed of lexical decisions.

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

    Science.gov (United States)

    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.

  1. In black South Africans from rural and urban communities, the 4G/5G PAI-1 polymorphism influences PAI-1 activity, but not plasma clot lysis time.

    Directory of Open Access Journals (Sweden)

    Zelda de Lange

    Full Text Available Data on genetic and environmental factors influencing PAI-1 levels and their consequent effect on clot lysis in black African populations are limited. We identified polymorphisms in the promoter area of the PAI-1 gene and determined their influence on PAI-1act levels and plasma clot lysis time (CLT. We also describe gene-environment interactions and the effect of urbanisation. Data from 2010 apparently healthy urban and rural black participants from the South African arm of the PURE study were cross-sectionally analysed. The 5G allele frequency of the 4G/5G polymorphism was 0.85. PAI-1act increased across genotypes in the urban subgroup (p = 0.009 but not significantly in the rural subgroup, while CLT did not differ across genotypes. Significant interaction terms were found between the 4G/5G polymorphism and BMI, waist circumference and triglycerides in determining PAI-1act, and between the 4G/5G polymorphism and fibrinogen and fibrinogen gamma prime in determining CLT. The C428T and G429A polymorphisms did not show direct relationships with PAI-1act or CLT but they did influence the association of other environmental factors with PAI-1act and CLT. Several of these interactions differed significantly between rural and urban subgroups, particularly in individuals harbouring the mutant alleles. In conclusion, although the 4G/5G polymorphism significantly affected PAI-1act, it contributed less than 1% to the PAI-1act variance. (Central obesity was the biggest contributor to PAI-1act variance (12.5%. Urbanisation significantly influenced the effect of the 4G/5G polymorphism on PAI-1act as well as gene-environment interactions for the C428T and G429A genotypes in determining PAI-1act and CLT.

  2. In black South Africans from rural and urban communities, the 4G/5G PAI-1 polymorphism influences PAI-1 activity, but not plasma clot lysis time.

    Science.gov (United States)

    de Lange, Zelda; Rijken, Dingeman C; Hoekstra, Tiny; Conradie, Karin R; Jerling, Johann C; Pieters, Marlien

    2013-01-01

    Data on genetic and environmental factors influencing PAI-1 levels and their consequent effect on clot lysis in black African populations are limited. We identified polymorphisms in the promoter area of the PAI-1 gene and determined their influence on PAI-1act levels and plasma clot lysis time (CLT). We also describe gene-environment interactions and the effect of urbanisation. Data from 2010 apparently healthy urban and rural black participants from the South African arm of the PURE study were cross-sectionally analysed. The 5G allele frequency of the 4G/5G polymorphism was 0.85. PAI-1act increased across genotypes in the urban subgroup (p = 0.009) but not significantly in the rural subgroup, while CLT did not differ across genotypes. Significant interaction terms were found between the 4G/5G polymorphism and BMI, waist circumference and triglycerides in determining PAI-1act, and between the 4G/5G polymorphism and fibrinogen and fibrinogen gamma prime in determining CLT. The C428T and G429A polymorphisms did not show direct relationships with PAI-1act or CLT but they did influence the association of other environmental factors with PAI-1act and CLT. Several of these interactions differed significantly between rural and urban subgroups, particularly in individuals harbouring the mutant alleles. In conclusion, although the 4G/5G polymorphism significantly affected PAI-1act, it contributed less than 1% to the PAI-1act variance. (Central) obesity was the biggest contributor to PAI-1act variance (12.5%). Urbanisation significantly influenced the effect of the 4G/5G polymorphism on PAI-1act as well as gene-environment interactions for the C428T and G429A genotypes in determining PAI-1act and CLT.

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

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    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.

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

    Science.gov (United States)

    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.

  5. STAT4 rs7574865 G/T and PTPN22 rs2488457 G/C polymorphisms influence the risk of developing juvenile idiopathic arthritis in Han Chinese patients.

    Science.gov (United States)

    Fan, Zhi-Dan; Wang, Fei-Fei; Huang, Hui; Huang, Na; Ma, Hui-Hui; Guo, Yi-Hong; Zhang, Ya-Yuan; Qian, Xiao-Qing; Yu, Hai-Guo

    2015-01-01

    Juvenile idiopathic arthritis (JIA) is a common autoimmune disease characterized by environmental influences along with several predisposing genes in the pathogenesis. The protein tyrosine phosphatase nonreceptor 22 (PTPN22) and signal transducer and activator of transcription factor 4 (STAT4) have been recognized as susceptibility genes for numerous autoimmune diseases. Associations of STAT4 rs7574865 G/T and PTPN22 (rs2488457 G/C and rs2476601 C/T) polymorphisms with JIA have repeatedly been replicated in several Caucasian populations. The aim of this study was to investigate the influence of three polymorphisms mentioned above on the risk of developing JIA in Han Chinese patients. Genotyping was performed on a total of 137 Chinese patients with JIA (JIA group) and 150 sex and age frequency-matched healthy volunteers (Control group). The single-nucleotide polymorphisms (SNP) were determined by using direct sequencing of PCR-amplified products. There were significant differences of PTPN22 rs2488457 G/C and STAT4 rs7574865 G/T polymorphisms between both groups. However, no significant difference was observed in distribution frequencies of PTPN22 rs2476601 polymorphism. The association with the PTPN22 rs2488457 G/C polymorphism remained significant in the stratifications by age at onset, ANA status, splenomegaly, lymphadenectasis and involvement joints. As with the STAT4 rs7574865 G/T polymorphisms, the enthesitis-related arthritis and presence of hepatomegaly had strong effect on the association. Our data strengthen STAT4 rs7574865 G/T and PTPN22 rs2488457 G/C polymorphisms as susceptibility factors for JIA.

  6. STAT4 rs7574865 G/T and PTPN22 rs2488457 G/C polymorphisms influence the risk of developing juvenile idiopathic arthritis in Han Chinese patients.

    Directory of Open Access Journals (Sweden)

    Zhi-Dan Fan

    Full Text Available Juvenile idiopathic arthritis (JIA is a common autoimmune disease characterized by environmental influences along with several predisposing genes in the pathogenesis. The protein tyrosine phosphatase nonreceptor 22 (PTPN22 and signal transducer and activator of transcription factor 4 (STAT4 have been recognized as susceptibility genes for numerous autoimmune diseases. Associations of STAT4 rs7574865 G/T and PTPN22 (rs2488457 G/C and rs2476601 C/T polymorphisms with JIA have repeatedly been replicated in several Caucasian populations. The aim of this study was to investigate the influence of three polymorphisms mentioned above on the risk of developing JIA in Han Chinese patients. Genotyping was performed on a total of 137 Chinese patients with JIA (JIA group and 150 sex and age frequency-matched healthy volunteers (Control group. The single-nucleotide polymorphisms (SNP were determined by using direct sequencing of PCR-amplified products. There were significant differences of PTPN22 rs2488457 G/C and STAT4 rs7574865 G/T polymorphisms between both groups. However, no significant difference was observed in distribution frequencies of PTPN22 rs2476601 polymorphism. The association with the PTPN22 rs2488457 G/C polymorphism remained significant in the stratifications by age at onset, ANA status, splenomegaly, lymphadenectasis and involvement joints. As with the STAT4 rs7574865 G/T polymorphisms, the enthesitis-related arthritis and presence of hepatomegaly had strong effect on the association. Our data strengthen STAT4 rs7574865 G/T and PTPN22 rs2488457 G/C polymorphisms as susceptibility factors for JIA.

  7. The influence of cytokine gene polymorphisms on the risk of developing gastric cancer in patients with Helicobacter pylori infection

    International Nuclear Information System (INIS)

    Stubljar, David; Jeverica, Samo; Jukic, Tomislav; Skvarc, Miha; Pintar, Tadeja; Tepes, Bojan; Kavalar, Rajko; Stabuc, Borut; Peterlin, Borut; Ihan, Alojz

    2015-01-01

    Helicobacter pylori infection is the main cause of gastric cancer. The disease progression is influenced by the host inflammatory responses, and cytokine single nucleotide polymorphisms (SNPs) may have a role in the course of the disease. The aim of our study was to investigate proinflammatory cytokine polymorphisms, previously associated with the development of gastric cancer, in a Slovenian population. In total 318 patients and controls were selected for the study and divided into three groups: (i) patients with gastric cancer (n = 58), (ii) patients with chronic gastritis (n = 60) and (iii) healthy control group (n = 200). H. pylori infection in patient groups was determined by serology, histology and culture. Four proinflammatory gene polymorphisms were determined (IL-1β, IL-1ra, TNF-α, TLR-4) in all subjects. We found a statistically significant difference between males and females for the groups (p = 0.025). Odds ratio (OR) for gastric cancer risk for females was 0.557 (95% confidence interval [CI]: 0.233–1.329) and for chronic gastritis 2.073 (95% CI: 1.005–4.277). IL-1B-511*T/T homozygous allele for cancer group had OR = 2.349 (95% CI: 0.583–9.462), heterozygous IL-1B-511*T had OR = 1.470 (95% CI: 0.583–3.709) and heterozygotes in TNF-A-308 genotype for chronic gastritis had OR = 1.402 (95% CI: 0.626–3.139). Other alleles had OR less than 1. We could not prove association between gastric cancer and chronic gastritis due to H. pylori in any cytokine SNPs studied in Slovenian population. Other SNPs might be responsible besides infection with H. pylori for the progression from atrophy to neoplastic transformation

  8. Influence of IL-1 gene polymorphism on the periodontal microbiota of HIV-infected Brazilian individuals

    OpenAIRE

    Gonçalves, Lucio de Souza; Ferreira, Sônia Maria Soares; Souza, Celso Oliveira; Colombo, Ana Paula Vieira

    2009-01-01

    This study investigated the association of IL-1A (+4845) and IL-1B (+3954) gene polymorphism with the subgingival microbiota and periodontal status of HIV-infected Brazilian individuals on highly active antiretroviral therapy (HAART). One hundred and five subjects were included in the study, distributed into 2 HIV groups [29 chronic periodontitis (CP+) and 30 periodontally healthy (H+)]; and 2 non-HIV groups (29 CP- and 17 H- patients). IL-1A and B were genotyped by PCR and restriction enzyme...

  9. Influence of Teflon substrate on crystallization and enzymatic degradation of polymorphic poly(butylene adipate)

    DEFF Research Database (Denmark)

    Ning, Zhenbo; Nielsen, Ronnie Bo Højstrup; Zhao, Lifen

    2014-01-01

    for PBA beta crystals between neither the oriented nor the non-oriented Teflon films. The enzymatic degradation rate of PBA films was not determined by the epitaxial crystallization, in fact it was still dependent on the polymorphic crystal structure of PBA. The morphological changes of PBA films after...... enzymatic degradation confirmed again that the epitaxial crystallization only occurred for the PBA film with alpha crystal structure which was produced by being sandwiched between oriented Teflon films, and it happened only on the surface of PBA films....

  10. The BDNF Val66Met Polymorphism Interacts with Maternal Parenting Influencing Adolescent Depressive Symptoms: Evidence of Differential Susceptibility Model.

    Science.gov (United States)

    Zhang, Leilei; Li, Zhi; Chen, Jie; Li, Xinying; Zhang, Jianxin; Belsky, Jay

    2016-03-01

    Although depressive symptoms are common during adolescence, little research has examined gene-environment interaction on youth depression. This study chose the brain-derived neurotrophic factor (BDNF) gene, tested the interaction between a functional polymorphism resulting amino acid substitution of valine (Val) to methionine (Met) in the proBDNF protein at codon 66 (Val66Met), and maternal parenting on youth depressive symptoms in a sample of 780 community adolescents of Chinese Han ethnicity (aged 11-17, M = 13.6, 51.3 % females). Participants reported their depressive symptoms and perceived maternal parenting. Results indicated the BDNF Val66Met polymorphism significantly moderated the influence of maternal warmth-reasoning, but not harshness-hostility, on youth depressive symptoms. Confirmatory model evaluation indicated that the interaction effect involving warmth-reasoning conformed to the differential-susceptibility rather than diathesis-stress model of person-X-environment interaction. Thus, Val carriers experienced less depressive symptoms than Met homozygotes when mothering was more positive but more symptoms when mothering was less positive. The findings provided evidence in support of the differential susceptibility hypothesis of youth depressive symptoms and shed light on the importance of examining the gene-environment interaction from a developmental perspective.

  11. Promoter polymorphisms in genes involved in porcine myogenesis influence their transcriptional activity.

    Science.gov (United States)

    Bongiorni, Silvia; Tilesi, Francesca; Bicorgna, Silvia; Iacoponi, Francesca; Willems, Daniela; Gargani, Maria; D'Andrea, MariaSilvia; Pilla, Fabio; Valentini, Alessio

    2014-11-07

    Success of meat production and selection for improvement of meat quality is among the primary aims in animal production. Meat quality traits are economically important in swine; however, the underlying genetic nature is very complex. Therefore, an improved pork production strongly depends on identifying and studying how genetic variations contribute to modulate gene expression. Promoters are key regions in gene modulation as they harbour several binding motifs to transcription regulatory factors. Therefore, polymorphisms in these regions are likely to deeply affect RNA levels and consequently protein synthesis. In this study, we report the identification of single nucleotide polymorphisms (SNPs) in promoter regions of candidate genes involved in development, cellular differentiation and muscle growth in Sus scrofa. We identified SNPs in the promoter regions of genes belonging to the Myogenic Regulatory Factors (MRF) gene family (the Myogenic Differentiation gene, MYOD1) and to Growth and Differentiation Factors (GDF) gene family (Myostatin gene, MSTN, GDF8), in Casertana and Large White breeds. The purpose of this study was to investigate if polymorphisms in the promoters could affect the transcriptional activity of these genes. With this aim, we evaluated in vitro the functional activity of the luciferase reporter gene luc2 activity, driven by two constructs carrying different promoter haplotypes. We tested the effects of the G302A (U12574) transition on the promoter efficiency in MYOD1 gene. We ascertained a difference in transcription efficiency for the two variants. A stronger activity of the A-carrying construct is more evident in C2C12. The luciferase expression driven by the MYOD1-A allelic variant displayed a 3.8-fold increased transcriptional activity. We investigated the activity of two haplotype variants (AY527152) in the promoter of GDF8 gene. The haploptype-1 (A435-A447-A879) up-regulated the expression of the reporter gene by a two-fold increase, and

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

    Science.gov (United States)

    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.

  13. Functional and prognostic influence of receptor polymorphisms in the vascular endothelial growth factor system in colorectal cancer

    DEFF Research Database (Denmark)

    Hansen, T; Spindler, K G; Aalund Olsen, Dorte

    2009-01-01

    was significantly higher than the median protein concentration of the CC genotype, p = 0.005. The CC genotype held prognostic information compared to CT and TT genotypes for both SNP's, pinfluence on the VEGFR-2 protein level, and the -604 T/C SNP...... on the gene expression level in CRC patients. The results furthermore indicate a prognostic influence of both SNP's on progression-free survival. No significant financial relationships to disclose.......e15032 Background: The vascular endothelial growth factor (VEGF) system plays a key role in the angiogenic process ensuring a sufficient blood supply to the growth of malignant tumours. The clinical importance of single nucleotide polymorphisms (SNP's) in the VEGF receptors is still unknown...

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

    Science.gov (United States)

    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

  15. Influence of plasminogen activator inhibitor-1 (SERPINE1) 4G/5G polymorphism on circulating SERPINE-1 antigen expression in HCC associated with viral infection.

    Science.gov (United States)

    Divella, Rosa; Mazzocca, Antonio; Gadaleta, Cosimo; Simone, Giovanni; Paradiso, Angelo; Quaranta, Michele; Daniele, Antonella

    2012-01-01

    Hepatocarcinogenesis is heavily influenced by chronic hepatitis B (HBV) and C (HCV) infection. Elevated levels of plasminogen activator inhibitor-1 (SERPINE1/PAI-1) have been reported in patients with hepatocellular carcinoma (HCC) associated with viral infection. The gene encoding SERPINE1 is highly polymorphic and the frequently associated 4/5 guanosine (4G/5G) polymorphism in the gene promoter may influence its expression. Here, we investigated the distribution of genotypes and the frequency of alleles of the 4G/5G polymorphism in patients with HCC, the influence of the 4G/5G polymorphism on plasma SERPINE1 levels and its association with viral infection. A total of 75 patients with HCC were enrolled: 32 (42.6%) were HBV(+)/HCV(+), 11 (14.6%) were only HCV(+), and 32 (42.6%) were negative for both viruses. A control group of healthy donors was also enrolled (n=50). SERPINE1 plasma concentrations were determined by ELISA and the detection of the promoter 4G/5G polymorphism was performed by an allele-specific PCR analysis. We found that the frequency of both the 4G/4G genotype (p=0.02) and the 4G allele (p=0.006) were significantly higher in patients with HCC compared to the control group, and particularly higher in patients with HCC co-infected with HBV(+)/HCV(+) than in those with no viral infection. We also found that patients with the 4G/4G genotype had significantly higher plasma SERPINE1 protein levels when compared with patients with the 4G/5G or 5G/5G genotype (p5G SERPINE1 polymorphism with a higher level of SERPINE1 protein in patients with HCC with HBV(+)/HCV(+) than those without infection, suggest the presence of two distinct pathogenic mechanisms in hepatocarcinogenesis, depending on the etiology.

  16. Influence of the HLA class II polymorphism in chronic Chagas' disease.

    Science.gov (United States)

    Fernandez-Mestre, M T; Layrisse, Z; Montagnani, S; Acquatella, H; Catalioti, F; Matos, M; Balbas, O; Makhatadze, N; Dominguez, E; Herrera, F; Madrigal, A

    1998-04-01

    Chagas' disease or American trypanosomiasis due to Trypanosoma cruzi has existed at least since the time of the Inca empire and contributes significantly to cardiovascular morbidity and mortality in several countries of this continent. Due to the fundamental role of human class II molecules polymorphic residues in the control of the immune response, a study was designed to define by DNA typing HLA class II alleles in a sample of 67 serologically positive individuals with and without cardiomyopathy and in 156 healthy controls of similar ethnic origin. Genomic DNA extraction, PCR amplification of the HLA-DRB1 and DQB1 second exon regions and hybridization to labelled specific probes were carried out following the 11th International Histocompatibility Workshop reference protocol. Comparison of DRB1 and DQB1 allele frequencies among the patients and control subjects showed a decreased frequency of DRB1*14 and DQB1*0303 in the patients, suggesting independent protective effects to the chronic infection in this population. Allele frequencies comparison between patients with and without cardiomyopathy showed a higher frequency of DRB1*01, DRB1*08 and DQB1*0501 and a decreased frequency of DRB1*1501 in the patients with arrhythmia and congestive heart failure. The results suggest that HLA Class II genes may be associated with the development of a chronic infection and with heart damage in Chagas' disease.

  17. Culture, distress, and oxytocin receptor polymorphism (OXTR) interact to influence emotional support seeking.

    Science.gov (United States)

    Kim, Heejung S; Sherman, David K; Sasaki, Joni Y; Xu, Jun; Chu, Thai Q; Ryu, Chorong; Suh, Eunkook M; Graham, Kelsey; Taylor, Shelley E

    2010-09-07

    Research has demonstrated that certain genotypes are expressed in different forms, depending on input from the social environment. To examine sensitivity to cultural norms regarding emotional support seeking as a type of social environment, we explored the behavioral expression of oxytocin receptor polymorphism (OXTR) rs53576, a gene previously related to socio-emotional sensitivity. Seeking emotional support in times of distress is normative in American culture but not in Korean culture. Consequently, we predicted a three-way interaction of culture, distress, and OXTR genotype on emotional support seeking. Korean and American participants (n = 274) completed assessments of psychological distress and emotional support seeking and were genotyped for OXTR. We found the predicted three-way interaction: among distressed American participants, those with the GG/AG genotypes reported seeking more emotional social support, compared with those with the AA genotype, whereas Korean participants did not differ significantly by genotype; under conditions of low distress, OXTR groups did not differ significantly in either cultural group. These findings suggest that OXTR rs53576 is sensitive to input from the social environment, specifically cultural norms regarding emotional social support seeking. These findings also indicate that psychological distress and culture are important moderators that shape behavioral outcomes associated with OXTR genotypes.

  18. Influence of interleukin-1β and interleukin-6 gene polymorphisms on the development of acute pancreatitis.

    Science.gov (United States)

    Chi, D Z; Chen, J; Huang, D P

    2015-02-03

    We investigated the association between 3 main proinflammatory cytokines [interleukin (IL)-1β and IL-6] and the risk of acute pancreatitis. Polymerase chain reaction-restriction fragment length polymorphism was used to genotype IL-1β+3954 C/T (rs1143634) and IL-1β-511 C/T (rs16944) and IL-6 -174 G/C (rs1800795) and IL-6 -634 C/G (rs1800796). The genotype distributions of IL-1β+3954 C/T (rs1143634) and IL-1β-511 C/T (rs16944) and IL-6 -174 G/C (rs1800795) and IL-6 -634 C/G (rs1800796) were in Hardy-Weinberg equilibrium for the control group. Multivariate regression analyses showed that subjects carrying the rs1143634 TT genotype had a significantly increased risk of acute pancreatitis, with an adjusted odds ratio (95% confidence interval) of 2.11 (1.03-4.51). Subjects carrying the IL-1β rs1143634 TT genotype had a significantly increased risk of acute pancreatitis in our Chinese population.

  19. Common polymorphisms influencing serum uric acid levels contribute to susceptibility to gout, but not to coronary artery disease.

    Directory of Open Access Journals (Sweden)

    Klaus Stark

    2009-11-01

    Full Text Available Recently, a large meta-analysis including over 28,000 participants identified nine different loci with association to serum uric acid (UA levels. Since elevated serum UA levels potentially cause gout and are a possible risk factor for coronary artery disease (CAD and myocardial infarction (MI, we performed two large case-control association analyses with participants from the German MI Family Study. In the first study, we assessed the association of the qualitative trait gout and ten single nucleotide polymorphisms (SNP markers that showed association to UA serum levels. In the second study, the same genetic polymorphisms were analyzed for association with CAD.A total of 683 patients suffering from gout and 1,563 healthy controls from the German MI Family Study were genotyped. Nine SNPs were identified from a recently performed genome-wide meta-analysis on serum UA levels (rs12129861, rs780094, rs734553, rs2231142, rs742132, rs1183201, rs12356193, rs17300741 and rs505802. Additionally, the marker rs6855911 was included which has been associated with gout in our cohort in a previous study. SNPs rs734553 and rs6855911, located in SLC2A9, and SNP rs2231142, known to be a missense polymorphism in ABCG2, were associated with gout (p=5.6*10(-7, p=1.1*10(-7, and p=1.3*10(-3, respectively. Other SNPs in the genes PDZK1, GCKR, LRRC16A, SLC17A1-SLC17A3, SLC16A9, SLC22A11 and SLC22A12 failed the significance level. None of the ten markers were associated with risk to CAD in our study sample of 1,473 CAD cases and 1,241 CAD-free controls.SNP markers in SLC2A9 and ABCG2 genes were found to be strongly associated with the phenotype gout. However, not all SNP markers influencing serum UA levels were also directly associated with the clinical manifestation of gout in our study sample. In addition, none of these SNPs showed association with the risk to CAD in the German MI Family Study.

  20. Common polymorphisms influencing serum uric acid levels contribute to susceptibility to gout, but not to coronary artery disease.

    Science.gov (United States)

    Stark, Klaus; Reinhard, Wibke; Grassl, Martina; Erdmann, Jeanette; Schunkert, Heribert; Illig, Thomas; Hengstenberg, Christian

    2009-11-05

    Recently, a large meta-analysis including over 28,000 participants identified nine different loci with association to serum uric acid (UA) levels. Since elevated serum UA levels potentially cause gout and are a possible risk factor for coronary artery disease (CAD) and myocardial infarction (MI), we performed two large case-control association analyses with participants from the German MI Family Study. In the first study, we assessed the association of the qualitative trait gout and ten single nucleotide polymorphisms (SNP) markers that showed association to UA serum levels. In the second study, the same genetic polymorphisms were analyzed for association with CAD. A total of 683 patients suffering from gout and 1,563 healthy controls from the German MI Family Study were genotyped. Nine SNPs were identified from a recently performed genome-wide meta-analysis on serum UA levels (rs12129861, rs780094, rs734553, rs2231142, rs742132, rs1183201, rs12356193, rs17300741 and rs505802). Additionally, the marker rs6855911 was included which has been associated with gout in our cohort in a previous study. SNPs rs734553 and rs6855911, located in SLC2A9, and SNP rs2231142, known to be a missense polymorphism in ABCG2, were associated with gout (p=5.6*10(-7), p=1.1*10(-7), and p=1.3*10(-3), respectively). Other SNPs in the genes PDZK1, GCKR, LRRC16A, SLC17A1-SLC17A3, SLC16A9, SLC22A11 and SLC22A12 failed the significance level. None of the ten markers were associated with risk to CAD in our study sample of 1,473 CAD cases and 1,241 CAD-free controls. SNP markers in SLC2A9 and ABCG2 genes were found to be strongly associated with the phenotype gout. However, not all SNP markers influencing serum UA levels were also directly associated with the clinical manifestation of gout in our study sample. In addition, none of these SNPs showed association with the risk to CAD in the German MI Family Study.

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

    Science.gov (United States)

    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

  2. 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

  3. CYP3A5 polymorphisms in renal transplant recipients: influence on tacrolimus treatment

    Directory of Open Access Journals (Sweden)

    Chen L

    2018-03-01

    Full Text Available Lucy Chen,1 G V Ramesh Prasad2 1Kidney Transplant Program, St Michael’s Hospital, Toronto, ON, Canada; 2Division of Nephrology, St Michael’s Hospital, Toronto, ON, Canada Abstract: Tacrolimus is a commonly used immunosuppressant after kidney transplantation. It has a narrow therapeutic range and demonstrates wide interindividual variability in pharmacokinetics, leading to potential underimmunosuppression or toxicity. Genetic polymorphism in CYP3A5 enzyme expression contributes to differences in tacrolimus bioavailability between individuals. Individuals carrying one or more copies of the wild-type allele *1 express CYP3A5, which increases tacrolimus clearance. CYP3A5 expressers require 1.5 to 2-fold higher tacrolimus doses compared to usual dosing to achieve therapeutic blood concentrations. Individuals with homozygous *3/*3 genotype are CYP3A5 nonexpressers. CYP3A5 nonexpression is the most frequent phenotype in most ethnic populations, except blacks. Differences between CYP3A5 genotypes in tacrolimus disposition have not translated into differences in clinical outcomes, such as acute rejection and graft survival. Therefore, although genotype-based dosing may improve achievement of therapeutic drug concentrations with empiric dosing, its role in clinical practice is unclear. CYP3A5 genotype may predict differences in absorption of extended-release and immediate-release oral formulations of tacrolimus. Two studies found that CYP3A5 expressers require higher doses of tacrolimus in the extended-release formulation compared to immediate release. CYP3A5 genotype plays a role in determining the impact of interacting drugs, such as fluconazole, on tacrolimus pharmacokinetics. Evidence conflicts regarding the impact of CYP3A5 genotype on risk of nephrotoxicity associated with tacrolimus. Further study is required. Keywords: calcineurin inhibitor, graft, pharmacogenomics, kidney, genotype

  4. Oxytocin gene polymorphisms influence human dopaminergic function in a sex-dependent manner.

    Science.gov (United States)

    Love, Tiffany M; Enoch, Mary-Anne; Hodgkinson, Colin A; Peciña, Marta; Mickey, Brian; Koeppe, Robert A; Stohler, Christian S; Goldman, David; Zubieta, Jon-Kar

    2012-08-01

    Oxytocin, classically involved in social and reproductive activities, is increasingly recognized as an antinociceptive and anxiolytic agent, effects which may be mediated via oxytocin's interactions with the dopamine system. Thus, genetic variation within the oxytocin gene (OXT) is likely to explain variability in dopamine-related stress responses. As such, we examined how OXT variation is associated with stress-induced dopaminergic neurotransmission in a healthy human sample. Fifty-five young healthy volunteers were scanned using [¹¹C]raclopride positron emission tomography while they underwent a standardized physical and emotional stressor that consisted of moderate levels of experimental sustained deep muscle pain, and a baseline, control state. Four haplotype tagging single nucleotide polymorphisms located in regions near OXT were genotyped. Measures of pain, affect, anxiety, well-being and interpersonal attachment were also assessed. Female rs4813625 C allele carriers demonstrated greater stress-induced dopamine release, measured as reductions in receptor availability from baseline to the pain-stress condition relative to female GG homozygotes. No significant differences were detected among males. We also observed that female rs4813625 C allele carriers exhibited higher attachment anxiety, higher trait anxiety and lower emotional well-being scores. In addition, greater stress-induced dopamine release was associated with lower emotional well-being scores in female rs4813625 C allele carriers. Our results suggest that variability within the oxytocin gene appear to explain interindividual differences in dopaminergic responses to stress, which are shown to be associated with anxiety traits, including those linked to attachment style, as well as emotional well-being in women. Copyright © 2012 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

  5. Influence of 677 C→T Polymorphism of Methylenetetrahydrofolate Reductase on Medium-Term Prognosis after Acute Coronary Syndromes

    OpenAIRE

    García-Pinilla, José M.; Espinosa-Caliani, Salvador; Jiménez-Navarro, Manuel; Gómez-Doblas, Juan J.; Cabrera-Bueno, Fernando; Reyes-Engel, Armando; de Teresa-Galván, Eduardo

    2007-01-01

    Various common genotypes of the polymorphism 677 C→T of the methylenetetrahydrofolate reductase enzyme result in lower activity of the enzyme and in a subsequent increase in homocysteine levels. Many studies have analyzed the connection between this polymorphism and the beginning of coronary artery disease. However, conclusions have been controversial, and evidence of a connection between this polymorphism and the prognosis of coronary artery disease has been poorly evaluated.

  6. Alcohol and aldehyde dehydrogenase gene polymorphisms influence susceptibility to esophageal cancer in Japanese alcoholics.

    Science.gov (United States)

    Yokoyama, A; Muramatsu, T; Omori, T; Matsushita, S; Yoshimizu, H; Higuchi, S; Yokoyama, T; Maruyama, K; Ishii, H

    1999-11-01

    Studies have consistently demonstrated that inactive aldehyde dehydrogenase-2 (ALDH2), encoded by ALDH2*1/2*2, is closely associated with alcohol-related carcinogenesis. Recently, the contributions of alcohol dehydrogenase-2 (ADH2) polymorphism to alcoholism, esophageal cancer, and the flushing response have also been described. To determine the effects of ALDH2 and ADH2 genotypes in genetically based cancer susceptibility, lymphocyte DNA samples from 668 Japanese alcoholic men more than 40 years of age (91 with and 577 without esophageal cancer) were genotyped and the results were expressed as odds ratios (ORs). This study also tested 82 of the alcoholics with esophageal cancer to determine whether cancer susceptibility is associated with patients' responses to simple questions about current or former flushing after drinking a glass of beer. The frequencies of ADH2*1/2*1 and ALDH2*1/2*2 were significantly higher in alcoholics with, than in those without, esophageal cancer (0.473 vs. 0.289 and 0.560 vs. 0.099, respectively). After adjustment for drinking and smoking, the analysis showed significantly increased cancer risk for alcoholics with either ADH2*1/2*I (OR = 2.03) or ALDH2*1/2*2 (OR = 12.76). For those having ADH2*1/2*1 combined with ALDH2*1/2*2, the esophageal cancer risk was enhanced in a multiplicative fashion (OR = 27.66). Responses to flushing questions showed that only 47.8% of the ALDH2*1/2*2 heterozygotes with ADH2*1/ 2*1, compared with 92.3% of those with ALDH2*1/2*2 and the ADH2*2 allele, reported current or former flushing. Genotyping showed that for alcoholics who reported ever flushing, the questionnaire was 71.4% correct in identifying ALDH2*1/2*2 and 87.9% correct in identifying ALDH2*1/2*1. Japanese alcoholics can be divided into cancer susceptibility groups on the basis of their combined ADH2 and ALDH2 genotypes. The flushing questionnaire can predict high risk ALDH2*1/2*2 fairly accurately in persons with ADH2*2 allele, but a reliable

  7. 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

  8. Influence of vitamin D receptor polymorphisms on biochemical markers of mineral bone disorders in South African patients with chronic kidney disease.

    Science.gov (United States)

    Waziri, Bala; Dix-Peek, Therese; Dickens, Caroline; Duarte, Raquel; Naicker, Saraladevi

    2018-02-07

    It remains unclear whether genetic factors may explain the reported variation in the levels of biochemical markers of chronic kidney disease mineral and bone disorders (CKD- MBD) across ethnic groups. Therefore, the aim of this study was to examine the influence of vitamin D receptor (VDR) polymorphisms on secondary hyperparathyroidism and its association with vitamin D levels in black and white South African study participants. This was a cross sectional study involving 272 CKD stage 3- 5D patients and 90 healthy controls. The four major VDR polymorphisms (Bsm 1, Fok 1, Taq 1, and Apa1) were genotyped using the polymerase chain reaction- restriction fragment length polymorphism (PCR -RFLP) method. In addition, biochemical markers of CKD-MBD were measured to determine their associations with the four VDR polymorphisms. With the exception of Taq I polymorphism, the distribution of the VDR polymorphisms differed significantly between blacks and whites. In hemodialysis patients, the Bb genotype was significantly associated with moderate secondary hyperparathyroidism (OR, 3.88; 95 CI 1.13-13.25, p = 0.03) and severe hyperparathyroidism (OR, 2.54; 95 CI 1.08-5.96, p = 0.03). This was consistent with the observed higher levels of median parathyroid hormone, fibroblast growth factor 23 and mean phosphate in patients with Bb genotype. This candidate risk genotype (Bb) was over represented in blacks compared to whites (71.0% versus 55.6%, p kidney disease. In addition, study participants with FokFf genotype are at increased of developing severe 25 -hydroxyvitamin D [25(OH)D] deficiency.

  9. Influence of The -202 A/C insulin-like growth factor-binding protein-3 promoter polymorphism on individual variation in height in Korean girls

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    Min Ju Yi

    2017-03-01

    Full Text Available PurposeThe most common single nucleotide polymorphism in the IGFBP3 promoter region occurs at position -202. This polymorphic variation occurs frequently and may influence growth hormone responsiveness and somatic growth. However, the effects of IGFBP3 promoter polymorphism on growth in children are unknown.MethodsRestriction fragment length polymorphism-based genotyping of the -202 single nucleotide polymorphism was performed in 146 Korean girls aged between 15 and 16 years, who were selected randomly from the Seoul School Health Promotion Center. The participants were divided into 3 groups (tall, medium, and short according to the height percentile established from normal reference values for Korean children. The serum levels of insulin-like growth factor I (IGF-I and IGF-binding protein-3 (IGFBP-3 were then compared according to genotype.ResultsThe genotype distribution in the participants was 79 AA (54.1%, 60 AC (41.1%, and 7 CC (4.8%. The C allele frequency at the -202 IGFBP3 position was 25.4% in this group. The mean serum IGFBP-3 concentration in girls with the AA genotype was higher than that in girls with the AC genotype in the medium (P=0.047 and short (P=0.035 groups, respectively. There was no difference in the IGF-I to IGFBP-3 molar ratio between the AA and AC genotype groups (P=0.161.ConclusionIn conclusion, the -202 polymorphism in the IGFBP3 promoter region is assumed to affect the serum concentration of IGFBP-3 in children as well as in adults. However, it is unclear whether this affects physical development according to the concentration of IGFBP-3.

  10. A Polymorphic Enhancer near GREM1 Influences Bowel Cancer Risk through Differential CDX2 and TCF7L2 Binding

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    Annabelle Lewis

    2014-08-01

    Full Text Available A rare germline duplication upstream of the bone morphogenetic protein antagonist GREM1 causes a Mendelian-dominant predisposition to colorectal cancer (CRC. The underlying disease mechanism is strong, ectopic GREM1 overexpression in the intestinal epithelium. Here, we confirm that a common GREM1 polymorphism, rs16969681, is also associated with CRC susceptibility, conferring ∼20% differential risk in the general population. We hypothesized the underlying cause to be moderate differences in GREM1 expression. We showed that rs16969681 lies in a region of active chromatin with allele- and tissue-specific enhancer activity. The CRC high-risk allele was associated with stronger gene expression, and higher Grem1 mRNA levels increased the intestinal tumor burden in ApcMin mice. The intestine-specific transcription factor CDX2 and Wnt effector TCF7L2 bound near rs16969681, with significantly higher affinity for the risk allele, and CDX2 overexpression in CDX2/GREM1-negative cells caused re-expression of GREM1. rs16969681 influences CRC risk through effects on Wnt-driven GREM1 expression in colorectal tumors.

  11. The i148m Pnpla3 polymorphism influences serum adiponectin in patients with fatty liver and healthy controls

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    Valenti Luca

    2012-08-01

    Full Text Available Abstract Background Reduced adiponectin is implicated in the pathogenesis of nonalcoholic fatty liver disease (NAFLD and steatohepatitis (NASH, and the I148M Patatin-like phospholipase domain-containing 3 (PNPLA3 polymorphism predisposes to NAFLD and liver damage progression in NASH and chronic hepatitis C (CHC by still undefined mechanisms, possibly involving regulation of adipose tissue function. Aim of this study was to evaluate whether the I148M PNPLA3 polymorphism influences serum adiponectin in liver diseases and healthy controls. Methods To this end, we considered 144 consecutive Italian patients with NAFLD, 261 with CHC, 35 severely obese subjects, and 257 healthy controls with very low probability of steatosis, all with complete clinical and genetic characterization, including adiponectin (ADIPOQ genotype. PNPLA3 rs738409 (I148M and ADIPOQ genotypes were evaluated by Taqman assays, serum adiponectin by ELISA. Adiponectin mRNA levels were evaluated by quantitative real-time PCR in the visceral adipose tissue (VAT of 35 obese subjects undergoing bariatric surgery. Results Adiponectin levels were independently associated with the risk of NAFLD and with the histological severity of the disease. Adiponectin levels decreased with the number of 148 M PNPLA3 alleles at risk of NASH both in patients with NAFLD (p = 0.03, and in healthy subjects (p = 0.04. At multivariate analysis, PNPLA3 148 M alleles were associated with low adiponectin levels (ADIPOQ genotype (OR 1.67, 95% c.i. 1.07-2.1 for each 148 M allele. The p.148 M PNPLA3 variant was associated with decreased adiponectin mRNA levels in the VAT of obese patients (p PNPLA3 and ADIPOQ genotypes and viral features. Conclusions The I148M PNPLA3 variant is associated with adiponectin levels in patients with NAFLD and in healthy subjects, but in the presence of adiponectin resistance not in CHC patients. The I148M PNPLA3 genotype may represent a genetic determinant of serum

  12. Do polymorphisms in MDR1 and CYP3A5 genes influence the risk of cytogenetic relapse in patients with chronic myeloid leukemia on imatinib therapy?

    Science.gov (United States)

    Harivenkatesh, Natarajan; Kumar, Lalit; Bakhshi, Sameer; Sharma, Atul; Kabra, Madhulika; Velpandian, Thirumurthy; Gogia, Ajay; Shastri, Shivaram S; Gupta, Yogendra Kumar

    2017-09-01

    Influence of polymorphisms in the genes coding for imatinib transporters and metabolizing enzymes on cytogenetic relapse in patients with chronic myeloid leukemia (CML) is not known. One hundred and four patients (52 cases with cytogenetic relapse and 52 controls without relapse) with chronic-phase CML on imatinib therapy and have completed 5 years of follow-up were enrolled. The following single nucleotide polymorphisms (SNPs) were genotyped; C1236T, C3435T, G2677T/A in MDR1 gene and A6986G in CYP3A5 gene, using PCR-RFLP method and validated by direct gene sequencing. Imatinib trough levels were measured using LC-MS/MS. Patients with CC genotype for MDR1-C1236T polymorphism were at significantly higher risk for cytogenetic relapse [OR =4.382, 95% CI (1.145, 16.774), p = .022], while those with TT genotype for MDR1-C3435T polymorphism had significantly lower risk of relapse [OR =0.309, 95% CI (0.134, 0.708), p = .005]. Imatinib trough levels were lower in patients with relapse compared to those without relapse (1551.4 ± 1324.1 vs. 2154.2 ± 1358.3 ng/mL; p = .041). MDR1-C3435T genotype [adjusted-OR: 0.266; 95% CI (0.111, 0.636); p = .003] and trough levels (p = .014) were independent predictors of relapse in multivariate analysis. To conclude, C1236T and C3435T polymorphisms in MDR1 gene and trough levels significantly influence the risk of cytogenetic relapse. MDR1-C3435T genotype might emerge as a potential biomarker to predict the risk of cytogenetic relapse in patients with CML.

  13. Do gene polymorphism in IL-1β, TNF-α and IL-6 influence therapeutic response in patients with drug refractory epilepsy?

    Science.gov (United States)

    Tiwari, Prabhakar; Dwivedi, Rekha; Mansoori, Nasim; Alam, Rizwan; Chauhan, Ugam Kumari; Tripathi, Manjari; Mukhopadhyay, Asok Kumar

    2012-09-01

    Pro-inflammatory cytokines may play an important pathophysiological role in patients with epilepsy. To understand the role of genes encoding pro-inflammatory cytokines in epilepsy, this study aimed to evaluate the polymorphisms of the promoter regions of IL-1β-511C>T (rs16944), TNF-α-308G>A (rs1800629) and IL-6-174G>C (rs1800795) genes and to look into the interaction between these genes in influencing seizure susceptibility, seizure frequency and response to therapy. The comparative frequency of polymorphism was determined in rs16944, rs1800629 and rs1800795 using PCR-RFLP in a group of 120 persons with epilepsy (PWE) and 110 ethnically matched healthy subjects of comparable age and sex in the North Indian population. Alleles and genotypes of rs16944, rs1800629 and rs1800795 were not found to influence the odds ratio of having susceptibility to epilepsy. Also gene-gene interaction of possible nine combinations of these genes did not show any positive association with epilepsy. The genotype and allelic frequency of rs1800795 showed a significant association (prs16944 and rs1800629 were not found to have such effect. This study demonstrates that the rs16944, rs1800629 and rs1800795 polymorphism does not act as a strong susceptibility factor for epilepsy in North Indian population. The genotypic association of rs1800795 with seizure frequency and drug-refractory epilepsy raises the issue that a specific set of polymorphic genes can influence seizures and therapeutic response in epilepsy. Copyright © 2012 Elsevier B.V. All rights reserved.

  14. [The influence of interleukin gene polymorphism on the serum cytokine level in the patients presenting with chonic suppurative otitis media].

    Science.gov (United States)

    Baike, E V; Vitkovsky, Yu A; Dutova, A A

    The objective of the present work was to study the influence of allelic variant associations of 1-beta interleukin (C3953T, &511C, T31C), interleukin-6 (C174G), and tumour necrosis factor-alpha (G308A) gene polymorphisms on the serum cytokine level in the patients presenting with chronic suppurative otitis media. A total of 299 patients at the age varying from 16 to 55 years with this condition divided into three groups were examined. Group 1 was comprised of 146 patients suffering from the tubotympanic form of chronic suppurative otitis media (CSOM). Group 2 was composed of 153 patients with epitympanic antral form of this condition. The control group included 183 subjects who have never suffered pathological changes in the middle ear. Human genomic DNA was analyzed with the use of the polymerase chain reaction (PCR). The serum cytokine levels were measured by the solid-state enzyme immunoassay in the beginning and at the end of the treatment period. The study has demonstrated that 56.2% of the healthy residents of the trans-Baikal region had the C/T Il-1b (C3953T) genotype. 79.1% of the patients presenting with the carious carious-destructive form of chronic suppurative otitis media were the heterozygous carriers of the T511C gene of 1-beta interleukin and had the maximally high concentrations of this interleukin in the blood serum. A rise in the production of the pro-inflammatory mediator (IL-6) was found to be related to the severity of the inflammatory process in the middle ear. The TNF-alpha content in the patients with CSOM during the active period of the disease proved to increase by a factor of 6 in comparison with that in the subjects of the control group irrespective of the type of mutation.

  15. NOS1 ex1f-VNTR polymorphism influences prefrontal brain oxygenation during a working memory task.

    Science.gov (United States)

    Kopf, Juliane; Schecklmann, Martin; Hahn, Tim; Dresler, Thomas; Dieler, Alica C; Herrmann, Martin J; Fallgatter, Andreas J; Reif, Andreas

    2011-08-15

    Nitric oxide (NO) synthase produces NO, which serves as first and second messenger in neurons, where the protein is encoded by the NOS1 gene. A functional variable number of tandem repeats (VNTR) polymorphism in the promoter region of the alternative first exon 1f of NOS1 is associated with various functions of human behavior, for example increased impulsivity, while another, non-functional variant was linked to decreased verbal working memory and a heightened risk for schizophrenia. We therefore investigated the influence of NOS1 ex 1f-VNTR on working memory function as reflected by both behavioral measures and prefrontal oxygenation. We hypothesized that homozygous short allele carriers exhibit altered brain oxygenation in task-related areas, namely the dorsolateral and ventrolateral prefrontal cortex and the parietal cortex. To this end, 56 healthy subjects were stratified into a homozygous long allele group and a homozygous short allele group comparable for age, sex and intelligence. All subjects completed a letter n-back task (one-, two-, and three-back), while concentration changes of oxygenated (O(2)Hb) hemoglobin in the prefrontal cortex were measured with functional near-infrared spectroscopy (fNIRS). We found load-associated O(2)Hb increases in the prefrontal and parts of the parietal cortex. Significant load-associated oxygenation differences between the two genotype groups could be shown for the dorsolateral prefrontal cortex and the parietal cortex. Specifically, short allele carriers showed a significantly larger increase in oxygenation in all three n-back tasks. This suggests a potential compensatory mechanism, with task-related brain regions being more active in short allele carriers to compensate for reduced NOS1 expression. Copyright © 2011 Elsevier Inc. All rights reserved.

  16. Influence of Cremophor EL and genetic polymorphisms on the pharmacokinetics of paclitaxel and its metabolites using a mechanism-based model.

    Science.gov (United States)

    Fransson, Martin N; Gréen, Henrik; Litton, Jan-Eric; Friberg, Lena E

    2011-02-01

    The formulation vehicle Cremophor EL has previously been shown to affect paclitaxel kinetics, but it is not known whether it also affects the kinetics of paclitaxel metabolites. This information may be important for understanding paclitaxel metabolism in vivo and in the investigation of the role of genetic polymorphisms in the metabolizing enzymes CYP2C8 and CYP3A4/CYP3A5 and the ABCB1 transporter. In this study we used the population pharmacokinetic approach to explore the influence of predicted Cremophor EL concentrations on paclitaxel (Taxol) metabolites. In addition, correlations between genetic polymorphisms and enzyme activity with clearance of paclitaxel, its two primary metabolites, 6α-hydroxypaclitaxel and p-3'-hydroxypaclitaxel, and its secondary metabolite, 6α-p-3'-dihydroxypaclitaxel were investigated. Model building was based on 1156 samples from a study with 33 women undergoing paclitaxel treatment for gynecological cancer. Total concentrations of paclitaxel were fitted to a model described previously. One-compartment models characterized unbound metabolite concentrations. Total concentrations of 6α-hydroxypaclitaxel and p-3'-hydroxypaclitaxel were strongly dependent on predicted Cremophor EL concentrations, but this association was not found for 6α-p-3'-dihydroxypaclitaxel. Clearance of 6α-hydroxypaclitaxel (fraction metabolized) was significantly correlated (p < 0.05) to the ABCB1 allele G2677T/A. Individuals carrying the polymorphisms G/A (n = 3) or G/G (n = 5) showed a 30% increase, whereas individuals with polymorphism T/T (n = 8) showed a 27% decrease relative to those with the polymorphism G/T (n = 17). The correlation of G2677T/A with 6α-hydroxypaclitaxel has not been described previously but supports other findings of the ABCB1 transporter playing a part in paclitaxel metabolism.

  17. Age and gender differences in the influences of eNOS T-786C polymorphism on arteriosclerotic parameters in general population in Japan.

    Science.gov (United States)

    Hashimoto, Marowa; Miyai, Nobuyuki; Hattori, Sonomi; Iwahara, Akihiko; Utsumi, Miyoko; Arita, Mikio; Takeshita, Tatsuya

    2016-07-01

    The influence of T-786C polymorphism in the promoter region of endothelial nitric oxide synthase (eNOS) on arteriosclerotic parameters by age and gender were examined. Brachial-ankle pulse wave velocity (baPWV), heart-rate adjusted augmentation index (AIx@75), pulse pressure (PP) and albumin-creatinine ratio (ACR) were assessed as arteriosclerotic parameters in addition to non-high-density lipoprotein cholesterol (non-HDL-C) to HDL-C (non-HDL-C/HDL-C) ratio in 1499 participants. T-786C polymorphism (rs2070744) was screened using a TaqMan allelic discrimination assay. Analyses of covariance were carried. Women with the non-C allele showed significantly lower AIx@75 in participants aged gender differences, possibly involving antioxidative and/or endothelial signaling other than inflammatory signaling.

  18. Polymorphisms in Plasmodium vivax Circumsporozoite Protein (CSP) Influence Parasite Burden and Cytokine Balance in a Pre-Amazon Endemic Area from Brazil

    Science.gov (United States)

    Ribeiro, Bruno de Paulo; Cassiano, Gustavo Capatti; de Souza, Rodrigo Medeiros; Cysne, Dalila Nunes; Grisotto, Marcos Augusto Grigolin; de Azevedo dos Santos, Ana Paula Silva; Marinho, Cláudio Romero Farias; Machado, Ricardo Luiz Dantas; Nascimento, Flávia Raquel Fernandes

    2016-01-01

    Mechanisms involved in severe P. vivax malaria remain unclear. Parasite polymorphisms, parasite load and host cytokine profile may influence the course of infection. In this study, we investigated the influence of circumsporozoite protein (CSP) polymorphisms on parasite load and cytokine profile in patients with vivax malaria. A cross-sectional study was carried out in three cities: São Luís, Cedral and Buriticupu, Maranhão state, Brazil, areas of high prevalence of P. vivax. Interleukin (IL)-2, IL-4, IL-10, IL-6, IL-17, tumor necrosis factor alpha (TNF-α, interferon gamma (IFN-γ and transforming growth factor beta (TGF-β were quantified in blood plasma of patients and in supernatants from peripheral blood mononuclear cell (PBMC) cultures. Furthermore, the levels of cytokines and parasite load were correlated with VK210, VK247 and P. vivax-like CSP variants. Patients infected with P. vivax showed increased IL-10 and IL-6 levels, which correlated with the parasite load, however, in multiple comparisons, only IL-10 kept this association. A regulatory cytokine profile prevailed in plasma, while an inflammatory profile prevailed in PBMC culture supernatants and these patterns were related to CSP polymorphisms. VK247 infected patients showed higher parasitaemia and IL-6 concentrations, which were not associated to IL-10 anti-inflammatory effect. By contrast, in VK210 patients, these two cytokines showed a strong positive correlation and the parasite load was lower. Patients with the VK210 variant showed a regulatory cytokine profile in plasma, while those infected with the VK247 variant have a predominantly inflammatory cytokine profile and higher parasite loads, which altogether may result in more complications in infection. In conclusion, we propose that CSP polymorphisms is associated to the increase of non-regulated inflammatory immune responses, which in turn may be associated with the outcome of infection. PMID:26943639

  19. Influence of decreased fibrinolytic activity and plasminogen activator inhibitor-1 4G/5G polymorphism on the risk of venous thrombosis.

    Science.gov (United States)

    Vuckovic, Biljana A; Djeric, Mirjana J; Tomic, Branko V; Djordjevic, Valentina J; Bajkin, Branislav V; Mitic, Gorana P

    2018-01-01

    : Objective of our study is to determine whether decreased fibrinolytic activity or plasminogen activator inhibitor (PAI)-1 4G/5G polymorphism influence the risk of venous thrombosis.Our case-control study included 100 patients with venous thrombosis, and 100 random controls. When patients were compared with random controls, unconditional logistic regression was used to calculate odds ratios (ORs) with 95% confidence intervals (CIs).Decreased fibrinolytic activity yielded a 2.7-fold increase in risk for venous thrombosis than physiological fibrinolytic activity (OR 2.70; 95% CI 1.22-5.98), when comparing patients with random controls. Adjustment for several putative confounders did not change the estimate (OR 3.02; 95% CI 1.26-7.22). Analysis of venous thrombotic risk influenced by PAI-1 genotype, showed no influence of PAI-1 4G/5G gene variant in comparison with 5G/5G genotype (OR 0.57 95% CI; 0.27-1.20).Decreased fibrinolytic activity increased, whereas PAI-1 4G/5G polymorphism did not influence venous thrombosis risk in this study.

  20. Influence of DPYD Genetic Polymorphisms on 5-Fluorouracil Toxicities in Patients with Colorectal Cancer: A Meta-Analysis

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    Qiang Li

    2014-01-01

    Full Text Available Our meta-analysis aggregated existing results from relevant studies to comprehensively investigate the correlations between genetic polymorphisms in dihydropyrimidine dehydrogenase (DPYD gene and 5-fluorouracil (5-FU toxicities in patients with colorectal cancer (CRC. The MEDLINE (1966∼2013, the Cochrane Library Database (Issue 12, 2013, EMBASE (1980∼2013, CINAHL (1982∼2013, Web of Science (1945∼2013, and the Chinese Biomedical Database (CBM (1982∼2013 were searched without language restrictions. Meta-analyses were conducted with the use of STATA software (Version 12.0, Stata Corporation, College Station, TX, USA. Seven clinical cohort studies with a total of 946 CRC patients met our inclusion criteria, and NOS scores of each of the included studies were ≥5. Our findings showed that DPYD genetic polymorphisms were significantly correlated with high incidences of 5-FU-related toxicity in CRC patients. SNP-stratified analysis indicated that there were remarkable connections of IVS14+1G>A, 464T>A, and 2194G>A polymorphisms with the incidence of marrow suppression in CRC patients receiving 5-FU chemotherapy. Furthermore, we found that IVS14+1G>A, 496A>G, and 2194G>A polymorphisms were correlated with the incidence of gastrointestinal reaction. Ethnicity-stratified analysis also revealed that DPYD genetic polymorphisms might contribute to the development of marrow suppression and gastrointestinal reaction among Asians, but not among Caucasians. The present meta-analysis suggests that DPYD genetic polymorphisms may be correlated with the incidence of 5-FU-related toxicity in CRC patients.

  1. Genetic polymorphisms in MDR1 and CYP3A4 genes in Asians and the influence of MDR1 haplotypes on cyclosporin disposition in heart transplant recipients.

    Science.gov (United States)

    Chowbay, Balram; Cumaraswamy, Sivathasan; Cheung, Yin Bun; Zhou, Qingyu; Lee, Edmund J D

    2003-02-01

    Intestinal cytochrome P450 3A4 (CYP3A4) and P-glycoprotein (P-gp) both play a vital role in the metabolism of oral cyclosporine (CsA). We investigated the genetic polymorphisms in CYP3A4(promoter region and exons 5, 7 and 9) and MDR1 (exons 12, 21 and 26) genes and the impact of these polymorphisms on the pharmacokinetics of oral CsA in stable heart transplant patients (n = 14). CYP3A4 polymorphisms were rare in the Asian population and transplant patients. Haplotype analysis revealed 12 haplotypes in the Chinese, eight in the Malays and 10 in the Indians. T-T-T was the most common haplotype in all ethnic groups. The frequency of the homozygous mutant genotype at all three loci (TT-TT-TT) was highest in the Indians (31%) compared to 19% and 15% in the Chinese and Malays, respectively. In heart transplant patients, CsA exposure (AUC(0-4 h), AUC(0-12 h) and C(max)) was high in patients with the T-T-T haplotypes compared to those with C-G-C haplotypes. These findings suggest that haplotypes rather than genotypes influence CsA disposition in transplant patients.

  2. The A736V TMPRSS6 polymorphism influences hepcidin and iron metabolism in chronic hemodialysis patients: TMPRSS6 and hepcidin in hemodialysis

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    Pelusi Serena

    2013-02-01

    Full Text Available Abstract Background Aim of this study was to evaluate whether the A736V TMPRSS6 polymorphism, a major genetic determinant of iron metabolism in healthy subjects, influences serum levels of hepcidin, the hormone regulating iron metabolism, and erythropoiesis in chronic hemodialysis (CHD. Methods To this end, we considered 199 CHD patients from Northern Italy (157 with hepcidin evaluation, and 188 healthy controls without iron deficiency, matched for age and gender. Genetic polymorphisms were evaluated by allele specific polymerase chain reaction assays, and hepcidin quantified by mass spectrometry. Results Serum hepcidin levels were not different between the whole CHD population and controls (median 7.1, interquartile range (IQR 0.55-17.1 vs. 7.4, 4.5-17.9 nM, respectively, but were higher in the CHD subgroup after exclusion of subjects with relative iron deficiency (p = 0.04. In CHD patients, the A736V TMPRSS6 polymorphism influenced serum hepcidin levels in individuals positive for mutations in the HFE gene of hereditary hemochromatosis (p 30 ng/ml; n = 86, hepcidin was associated with lower mean corpuscular volume (p = 0.002, suggesting that it contributed to iron-restricted erythropoiesis. In line with previous results, in patients without acute inflammation and severe iron deficiency the “high hepcidin” 736 V TMPRSS6 variant was associated with higher erythropoietin maintenance dose (p = 0.016, independently of subclinical inflammation (p = 0.02. Conclusions The A736V TMPRSS6 genotype influences hepcidin levels, erythropoiesis, and anemia management in CHD patients. Evaluation of the effect of TMPRSS6 genotype on clinical outcomes in prospective studies in CHD may be useful to predict the outcomes of hepcidin manipulation, and to guide treatment personalization by optimizing anemia management.

  3. 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.

  4. Influence of the β-fibrinogen-455G/A polymorphism on development of ischemic stroke and coronary heart disease.

    Science.gov (United States)

    Gu, Lian; Liu, Wenhui; Yan, Yan; Su, Li; Wu, Guangliang; Liang, Baoyun; Tan, Jinjing; Huang, Guihua

    2014-06-01

    Ischemic stroke (IS) and coronary heart disease (CHD) are two vascular disorders that are a common cause of death worldwide. Several studies have assessed the association of the β-fibrinogen-455G/A (FGB-455G/A) polymorphism and risk of IS and CHD, but the results are still inconsistent. Our study aimed to investigate whether the FGB-455G/A polymorphism was associated with susceptibility to IS and CHD by using meta-analysis. Relevant studies were identified from PubMed, Embase and four Chinese database up to July 2013.Data were analyzed and processed by Stata 11.2. A pooled OR with 95% CI was calculated to estimate the strength of the genetic association. Cumulative meta-analysis was performed to assess the tendency of pooled OR over time. 45 studies based on a total of 7238 cases and 7395 controls were included in our meta-analysis. The results indicated that the FGB-455G/A polymorphism is associated with the risk of IS when compared with the dominant model (OR=1.518, 95%CI=1.279-1.802 for AA+GA vs. GG). In the subgroup analysis by ethnicity, significantly elevated risks were associated with the A allele in Asians (OR=1.700, 95%CI=1.417-2.040), but not in Caucasians (OR=0.942, 95%CI=0.813-1.091). Both the hypertension and non-hypertension subgroups reached significant results, but no significance was found when stratified according to sex or subtype of IS. Results indicate that the FGB-455G/A polymorphism is associated with CHD (OR=1.802, 95%CI=1.445-2.246). Our meta-analysis suggests that the FGB-455G/A polymorphism contributes to susceptibility to IS and CHD. Copyright © 2014 Elsevier Ltd. All rights reserved.

  5. The influence of a polymorphism in the gene encoding angiotensin converting enzyme (ACE on treatment outcomes in late-onset Pompe patients receiving alglucosidase alfa

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    Rena C. Baek

    2016-09-01

    Full Text Available Correlations between angiotensin-converting enzyme (ACE genotype (I/I, I/D, D/D, disease severity at baseline and response to enzyme replacement therapy (ERT were assessed in the Pompe disease Late-Onset Treatment Study (LOTS. No correlations were observed between ACE genotype and disease severity at baseline. However, D/D patients appeared to have a reduced response to alglucosidase alfa treatment than I/I or I/D patients, suggesting that ACE polymorphisms may influence the response to alglucosidase alfa treatment and warrants further investigation.

  6. 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....

  7. 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.

  8. Association between PER3 length polymorphism and onco-hematological diseases and its influences on patients' functionality

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    María Belén Cerliani

    2015-12-01

    Full Text Available Circadian clock gene PER3 and its length polymorphism may have a role in oncogenesis as clock genes act as key regulators of cell cycle and DNA repair pathways. The polymorphism may affect the condition of patients who show disrupted circadian rhythm due to tumor development. The aim was to assess the association between PER3 polymorphism and onco-hematological diseases, and analyze whether this variant has an impact on patient’s functionality. We conducted a case-control study on 125 patients with onco-hematological diseases and 310 control patients. PER3 allelic variants were detected by using polymerase chain reaction. Sociodemographic data and information on patient’s habits and functionality were obtained through questionnaire. Genotypes 4/5 + 5/5 showed an odd ratio (OR = 1.39, with no statistical significance. However, those genotypes were associated with a two-fold increase in the risk of acute/chronic lymphoblastic/myeloblastic leukemia, taken all together. The occurrence of “changes in humor during last two months” was significantly associated with onco-hematological diseases. “Fatigue on awakening” and “self-reported snore” were associated with cases carrying the 4/5 or 5/5 genotypes. The results suggested that PER3 polymorphism may have a role in the risk of leukemia, and might be a possible marker for individual differences in susceptibility to sleep disruption. This work provides insights for the identification of individuals at high risk of cancer, and those who are more susceptible to circadian disruption, which may decrease the physiological defenses against the tumor.

  9. Period3 VNTR polymorphism influences the time-of-day pain onset of acute myocardial infarction with ST elevation.

    Science.gov (United States)

    Lipkova, Jolana; Splichal, Zbynek; Bienertova-Vasku, Julie Anna; Jurajda, Michal; Parenica, Jiri; Vasku, Anna; Goldbergova, Monika Pavkova

    2014-10-01

    It is well established that the incidence and infarct size in acute myocardial infarction (AMI) is subject to circadian variations. At the molecular level, circadian clocks in distinct cells, including cardiomyocytes, generate 24-h cycles of biochemical processes. Possible imbalance or impairment in the cell clock mechanism may alter the cardiac metabolism and function and increase the susceptibility of cardiovascular diseases. One of the key components of the human clock system PERIOD3 (PER3) has been recently demonstrated to affect circadian expression of various genes in different tissues, including the heart. The variable number tandem repeat (VNTR) polymorphism (rs57875989) in gene Period3 (Per3) is related to multiple phenotypic parameters, including diurnal preference, sleep homeostasis, infection and cancer. The aim of our study was to investigate the effect of this polymorphism in AMI with ST elevation (STEMI). The study subjects (314 patients of Caucasian origin with STEMI, and 332 healthy controls) were genotyped for Per3 VNTR polymorphism using an allele-specific polymerase chain reaction. A gender difference in circadian rhythmicity of pain onset was observed with significant circadian pattern in men. Furthermore, the Per3(5/5) variant carriers were associated with higher levels of interleukin-6, B-type natriuretic peptide and lower vitamin A levels. By using cosinor analysis we observed different circadian distribution patterns of AMI onset at the level of genotype and allelic frequencies. Genotypes with at least one 4-repeat allele (Per3(4/5) and Per3(4/4)) (N = 264) showed remarkable circadian activity in comparison with Per3(5/5) (N = 50), especially in men. No significant differences in genotype and/or allele frequencies of Per3 VNTR polymorphism were observed when comparing STEMI cases and controls. Our results indicate that the Per3 VNTR may contribute to modulation of cardiac functions and interindividual differences in development and

  10. Influence of IL-1RN intron 2 variable number of tandem repeats (VNTR) polymorphism on bipolar disorder.

    Science.gov (United States)

    Rafiei, A; Hosseini, S H; Taheri, M; Hosseni-khah, Z; Hajilooi, M; Mazaheri, Z

    2013-01-01

    Several lines of evidence point to the role of neurobiological mechanisms and genetic background in bipolar disorder (BD). The interleukin-1 receptor antagonist (IL-1Ra) is the principal regulator of IL-1α and IL-1β bioactivities. This study aimed to investigate the potential role of the variable number of tandem repeats (VNTR) polymorphisms of the IL-1Ra gene (IL1RN) in conferring susceptibility to BD. In total, 217 patients meeting DSM-IV-TR criteria for BD and 212 controls were recruited for the study. Genotyping of IL1RN was determined by polymerase chain reaction amplification of VNTR of 86 base pairs in intron 2 of IL1RN. The genotype distribution of IL1RN polymorphism was significantly different between BD patients and controls. The IL1RN*1/2 genotype was more prevalent in BD patients than in controls (44.2 vs. 30.2%, p = 0.003). Multiple logistic regression analysis demonstrated that IL1RN*1/2 heterozygotes had a significantly higher risk for BD (OR 1.83 and 95% CI 1.22-2.74, p = 0.003). Further stratification of the BD patients into IL1RN*2 allele carrier and noncarrier subgroups revealed a strong association between IL1RN*2 carriage and prolongation of the disease (p = 0.02). These findings suggest a positive association between VNTR polymorphism in IL1RN and BD. Additional studies, particularly with a prospective approach, are necessary to clarify the precise role of the VNTR polymorphism on the disease in different ethnic populations. Copyright © 2013 S. Karger AG, Basel.

  11. [INFLUENCE OF AZOSPIRILLUM BRASILENSE 10/1 ON ASSOCIATIVE NITROGEN FIXATION AND INTRAVARIETAL POLYMORPHISM OF SPRING TRITICALE].

    Science.gov (United States)

    Patika, V P; Nadkernichna, O V; Shahovnina, O O

    2015-01-01

    It is shown, that the perspective Ukrainian sorts of spring triticale characterizes by considerable polymorphism by associative N2-fixing ability in root zone of plants. Application of active strain Azospirillum brasilense 10/1 promotes the decline of variability of this sign within the limits of sort, increase potential nitrogen activity is on the average in 3,2-4,7 times and also distributing normalizations in the selections of the inoculated plants.

  12. ATF5 polymorphisms influence ATF function and response to treatment in children with childhood acute lymphoblastic leukemia

    OpenAIRE

    Rousseau, Julie; Gagné, Vincent; Labuda, Malgorzata; Beaubois, Cyrielle; Sinnett, Daniel; Laverdière, Caroline; Moghrabi, Albert; Sallan, Stephen E.; Silverman, Lewis B.; Neuberg, Donna; Kutok, Jeffery L.; Krajinovic, Maja

    2011-01-01

    Asparaginase is a standard and critical component in the therapy of childhood acute lymphoblastic leukemia. Asparagine synthetase (ASNS) and the basic region leucine zipper activating transcription factor 5 (ATF5) and arginosuccinate synthase 1 (ASS1) have been shown to mediate the antileukemic effect of asparaginase and to display variable expression between leukemia cells that are resistant and sensitive to treatment. Fourteen polymorphisms in the regulatory and coding regions of these gene...

  13. Androgen receptor CAG repeat polymorphism and epigenetic influence among the south Indian women with Polycystic Ovary Syndrome.

    Directory of Open Access Journals (Sweden)

    Shilpi Dasgupta

    Full Text Available The present study was carried out to assess the role of androgen receptor CAG repeat polymorphism and X chromosome inactivation (XCI pattern among Indian PCOS women and controls which has not been hitherto explored and also to test the hypothesis that shorter CAG alleles would be preferentially activated in PCOS. CAG repeat polymorphism and X chromosome methylation patterns were compared between PCOS and non-PCOS women. 250 PCOS women and 299 controls were included for this study. Androgen receptor CAG repeat sizes, XCI percentages, and clinical and biochemical parameters were measured. The mean CAG repeat number is similar between the cases (18.74±0.13 and controls (18.73±0.12. The obese PCOS women were significantly more frequent in the 20 CAG repeat category than the lean PCOS women, yielding a highly significant odds (p=0.001. Among the women with non-random X-inactivation, alleles with <19 repeats were more frequently activated among cases than controls (p=0.33. CAG repeat polymorphism by itself cannot be considered as a useful marker for discriminating PCOS. We observed a trend of preferential activation of the shorter allele among the PCOS cases with non random XCI pattern. In the obese PCOS women, this microsatellite variation may account for the hyperandrogenicity to a larger extent than the lean PCOS women.

  14. Influence of Angiotensin-Converting-Enzyme Gene Polymorphism on Echocardiographic Data of Patients with Ischemic Heart Failure

    Science.gov (United States)

    Duque, Gustavo Salgado; da Silva, Dayse Aparecida; de Albuquerque, Felipe Neves; Schneider, Roberta Siuffo; Gimenez, Alinne; Pozzan, Roberto; Rocha, Ricardo Mourilhe; de Albuquerque, Denilson Campos

    2016-01-01

    Background Association between angiotensin-converting-enzyme (ACE) gene polymorphisms and different clinical and echocardiographic outcomes has been described in patients with heart failure (HF) and coronary artery disease. Studying the genetic profile of the local population with both diseases is necessary to assess the occurrence of that association. Objectives To assess the frequency of ACE gene polymorphisms in patients with ischemic HF in a Rio de Janeiro population, as well as its association with echocardiographic findings. Methods Genetic assessment of I/D ACE polymorphism in association with clinical, laboratory and echocardiographic analysis of 99 patients. Results The allele frequency was: 53 I alleles, and 145 D alleles. Genotype frequencies were: 49.5% DD; 47.48% DI; 3.02% II. Drug treatment was optimized: 98% on beta-blockers, and 84.8% on ACE inhibitors or angiotensin-receptor blocker. Echocardiographic findings: difference between left ventricular diastolic diameters (ΔLVDD) during follow-up: 2.98±8.94 (DD) vs. 0.68±8.12 (DI) vs. -11.0±7.00 (II), p=0.018; worsening during follow-up of the LV systolic diameter (LVSD): 65.3% DD vs. 19.0% DI vs. 0.0% II, p=0.01; of the LV diastolic diameter (LVDD): 65.3% DD vs. 46.8% DI vs. 0.0% II, p=0.03; and of the LV ejection fraction (LVEF): 67.3% DD vs. 40.4% DI vs. 33.3% II, p=0.024. Correlated with D allele: ΔLVEF, ΔLVSD, ΔLVDD. Conclusions More DD genotype patients had worsening of the LVEF, LVSD and LVDD, followed by DI genotype patients, while II genotype patients had the best outcome. The same pattern was observed for ΔLVDD. PMID:27812677

  15. Influence of matrix metalloproteinase gene polymorphisms in healthy North Indians compared to variations in other ethnic groups worldwide.

    Science.gov (United States)

    Srivastava, Priyanka; Kapoor, Rakesh; Mittal, Rama Devi

    2009-01-01

    Matrix metalloproteinases have a range of biological functions, including the liberation of cytokines and membrane-bound receptors, with roles in promotion of tumor invasion and angiogenesis. Several polymorphisms in MMPs have been implicated in the development of cancer as well as other diseases. Since their frequency distributions in the general North Indian population is not known the present study was conducted with the focus on MMP-1(-519) Aandgt; G, MMP-1(-1607) 1Gandgt; 2G, and MMP-7(-181) Aandgt; G gene polymorphisms. PCR-based analysis was conducted for 200 normal healthy individuals of similar ethnicity. Allelic frequencies in wild type of MMP-1(-519) Aandgt; G were 71.2% A; MMP-1(-1607) 1Gandgt; 2G 48.2% 1G; MMP-7(-181) Aandgt; G 60.7% A. The variant allele frequencies were 29% A in MMP-1(-519) Aandgt; G; 52% 2G in MMP-1(-1607) 1Gandgt; 2G; and 39.3% G in MMP-7(-181) Aandgt; G respectively. We further compared frequency distribution for these genes with various published studies in different ethnicity globally. Our results suggest that frequency in these MMP genes exhibit distinctive patterns in India that could perhaps be attributed to ethnic variation. This study is important as it can form a baseline for screening individuals who are at high risk when exposed to environmental carcinogens. More emphasis is needed on evaluating polymorphisms, alone or in combination, as modifiers of risk from relevant environmental/lifestyle exposures.

  16. Influence of melatonin receptor 1A gene polymorphisms on seasonal reproduction in Sarda ewes with different body condition scores and ages.

    Science.gov (United States)

    Mura, M C; Luridiana, S; Bodano, S; Daga, C; Cosso, G; Diaz, M L; Bini, P P; Carcangiu, V

    2014-10-01

    In several species, circadian changes in melatonin concentrations play a key role in the photoperiodic control of seasonality. In sheep, two silent mutations in the melatonin receptor 1A gene (MTNR1A) at positions 606 and 612 of the exon II are associated with seasonal reproduction. However, in some sheep breeds, no relationships have been found between MTNR1A polymorphisms and reproductive seasonality. This lack of relationship could be due to effects of breed, body condition, age, and/or environmental conditions. Thus, the present study was conducted with the Sarda sheep breed with the aim of documenting the effect of MTNR1A gene polymorphisms on reproductive resumption and to evaluate whether such this effect was modified by differences in body condition score (BCS) and age. Six hundred three- to six-year-old multiparous ewes with BCSs between 2.5 and 3.5 were selected. Genomic DNA was extracted and subjected to PCR to amplify the ovine exon II of the MTNR1A gene. The amplicons were subjected to digestion with the restriction enzymes RsaI and MnlI to detect the T606C and A612G polymorphisms, respectively. Ewes carrying the G/G, G/A, C/C, and C/T genotypes exhibited higher fertility rates (Preproductive resumption in the Sarda sheep breed. Moreover, the data also indicated that, over the limited ranges evaluated in this study, BCS and age had no significant influence on reproductive activity. Copyright © 2014 Elsevier B.V. All rights reserved.

  17. Biological monitoring and the influence of genetic polymorphism of As3MT and GSTs on distribution of urinary arsenic species in occupational exposure workers.

    Science.gov (United States)

    Janasik, Beata; Reszka, Edyta; Stanislawska, Magdalena; Wieczorek, Edyta; Fendler, Wojciech; Wasowicz, Wojciech

    2015-08-01

    To examine the differences in urinary arsenic metabolism patterns in men affected by occupational exposure, we performed a study on 149 participants—workers of a copper mill and 52 healthy controls without occupational exposure. To elucidate the role of genetic factors in arsenic (As) metabolism, we studied the associations of six polymorphisms: As3MT Met287Thr (T>C) in exon 9; As3MT A>G in 5'UTR; As3MT C>G in intron 6; As3MT T>G in intron 1; GSTP1 Ile105Val and GSTO2 T>C. Air samples were collected using individual samplers during work shift. Urine samples were analyzed for total arsenic and arsenic chemical forms (As(III); As(V), MMA, DMA, AsB) using HPLC-ICP-MS. A specific polymerase chain reaction was done for the amplification of exons and flanking regions of As3MT and GSTs. The geometric mean arsenic concentrations in the air were 27.6 ± 4.9 µg/m(3). A significant correlation (p iAs +MMA and iAs. As3MT (rs3740400) GG homozygotes showed significantly (p iAs (21.8 ± 2.0) in urine than GC+CC heterozygotes (16.0 ± 2.1). A strong association between the gene variants and As species in urine was observed for GSTO2 (rs156697) polymorphism. The findings of the study point out that the concentration of iAs or the sum of iAs + MMA in urine can be a reliable biological indicator of occupational exposure to arsenic. This study demonstrates that As3MT and/or GSTs genotype may influence As metabolism. Nevertheless, further studies investigating genetic polymorphism in occupational conditions are required.

  18. The Association of PPARγ Pro12Ala and C161T Polymorphisms with Polycystic Ovary Syndrome and Their Influence on Lipid and Lipoprotein Profiles

    Directory of Open Access Journals (Sweden)

    Zohreh Rahimi

    2018-05-01

    Full Text Available Background The aim of present study was to clarify the role of the peroxisome proliferator-activated receptor (PPAR γ Pro12Ala and C161T polymorphisms in the pathogenesis of polycystic ovary syndrome (PCOS and their influence on lipid and lipoprotein profiles of patients. Materials and Methods The present cross-sectional study consisted of 50 women with PCOS, who referred to the Kermanshah University of Medical Sciences Clinic between April and October 2015, and 233 unrelated age-matched healthy women from the same region (West Iran. The PPARγ Pro12Ala and PPARγ C161T polymorphisms were gen- otyped using the polymerase chain reaction-restriction fragment length polymorphism method. Fasting blood sugar (FBS, serum triglycerides (TG, cholesterol, low density lipoprotein- cholesterol (LDL-C, high density lipoprotein- cholesterol (HDL-C and estradiol levels were measured. Results The serum level of estradiol was significantly lower in PCOS patients compared to healthy women. The PPARγ Pro12Ala (CG genotype increased the risk of PCOS 2.96-fold. The frequency of the PPARγ T allele (at C161T was 21% in patients and 17.2% in controls with no significant difference (P=0.52. In all studied individuals, the PPARγ CG geno- type was associated with significantly higher levels of TG. However, significantly lower levels of total cholesterol and LDL-C were observed in PPARγ TT individuals compared with those with the CC genotype. Within the PCOS group, the PPARγ CG genotype was significantly associated with lower levels of estradiol compared with the CC genotype. Also, the CG genotype was significantly associated with higher levels of TG when compared with the CC genotype. Conclusion Our study shows that, unlike PPARγ C161T, PPARγ Pro12Ala is associated with the risk of PCOS. Also, we found that the lipid and lipoprotein profiles significantly vary based on PPARγ Pro12Ala and C161T genotypes.

  19. Interaction of motor training and intermittent theta burst stimulation in modulating motor cortical plasticity: influence of BDNF Val66Met polymorphism.

    Directory of Open Access Journals (Sweden)

    Mina Lee

    Full Text Available Cortical physiology in human motor cortex is influenced by behavioral motor training (MT as well as repetitive transcranial magnetic stimulation protocol such as intermittent theta burst stimulation (iTBS. This study aimed to test whether MT and iTBS can interact with each other to produce additive changes in motor cortical physiology. We hypothesized that potential interaction between MT and iTBS would be dependent on BDNF Val66Met polymorphism, which is known to affect neuroplasticity in the human motor cortex. Eighty two healthy volunteers were genotyped for BDNF polymorphism. Thirty subjects were assigned for MT alone, 23 for iTBS alone, and 29 for MT + iTBS paradigms. TMS indices for cortical excitability and motor map areas were measured prior to and after each paradigm. MT alone significantly increased the motor cortical excitability and expanded the motor map areas. The iTBS alone paradigm also enhanced excitability and increased the motor map areas to a slightly greater extent than MT alone. A combination of MT and iTBS resulted in the largest increases in the cortical excitability, and the representational motor map expansion of MT + iTBS was significantly greater than MT or iTBS alone only in Val/Val genotype. As a result, the additive interaction between MT and iTBS was highly dependent on BDNF Val66Met polymorphism. Our results may have clinical relevance in designing rehabilitative strategies that combine therapeutic cortical stimulation and physical exercise for patients with motor disabilities.

  20. Interaction of motor training and intermittent theta burst stimulation in modulating motor cortical plasticity: influence of BDNF Val66Met polymorphism.

    Science.gov (United States)

    Lee, Mina; Kim, Song E; Kim, Won Sup; Lee, Jungyeun; Yoo, Hye Kyung; Park, Kee-Duk; Choi, Kyoung-Gyu; Jeong, Seon-Yong; Kim, Byung Gon; Lee, Hyang Woon

    2013-01-01

    Cortical physiology in human motor cortex is influenced by behavioral motor training (MT) as well as repetitive transcranial magnetic stimulation protocol such as intermittent theta burst stimulation (iTBS). This study aimed to test whether MT and iTBS can interact with each other to produce additive changes in motor cortical physiology. We hypothesized that potential interaction between MT and iTBS would be dependent on BDNF Val66Met polymorphism, which is known to affect neuroplasticity in the human motor cortex. Eighty two healthy volunteers were genotyped for BDNF polymorphism. Thirty subjects were assigned for MT alone, 23 for iTBS alone, and 29 for MT + iTBS paradigms. TMS indices for cortical excitability and motor map areas were measured prior to and after each paradigm. MT alone significantly increased the motor cortical excitability and expanded the motor map areas. The iTBS alone paradigm also enhanced excitability and increased the motor map areas to a slightly greater extent than MT alone. A combination of MT and iTBS resulted in the largest increases in the cortical excitability, and the representational motor map expansion of MT + iTBS was significantly greater than MT or iTBS alone only in Val/Val genotype. As a result, the additive interaction between MT and iTBS was highly dependent on BDNF Val66Met polymorphism. Our results may have clinical relevance in designing rehabilitative strategies that combine therapeutic cortical stimulation and physical exercise for patients with motor disabilities.

  1. Evidence of Alternative Cystatin C Signal Sequence Cleavage Which Is Influenced by the A25T Polymorphism.

    Directory of Open Access Journals (Sweden)

    Annie Nguyen

    Full Text Available Cystatin C (Cys C is a small, potent, cysteine protease inhibitor. An Ala25Thr (A25T polymorphism in Cys C has been associated with both macular degeneration and late-onset Alzheimer's disease. Previously, studies have suggested that this polymorphism may compromise the secretion of Cys C. Interestingly, we found that untagged A25T, A25T tagged C-terminally with FLAG, or A25T FLAG followed by green fluorescent protein (GFP, were all secreted as efficiently from immortalized human cells as their wild-type (WT counterparts (e.g., 112%, 100%, and 88% of WT levels from HEK-293T cells, respectively. Supporting these observations, WT and A25T Cys C variants also showed similar intracellular steady state levels. Furthermore, A25T Cys C did not activate the unfolded protein response and followed the same canonical endoplasmic reticulum (ER-Golgi trafficking pathway as WT Cys C. WT Cys C has been shown to undergo signal sequence cleavage between residues Gly26 and Ser27. While the A25T polymorphism did not affect Cys C secretion, we hypothesized that it may alter where the Cys C signal sequence is preferentially cleaved. Under normal conditions, WT and A25T Cys C have the same signal sequence cleavage site after Gly26 (referred to as 'site 2' cleavage. However, in particular circumstances when the residues around site 2 are modified (such as by the presence of an N-terminal FLAG tag immediately after Gly26, or by a Gly26Lys (G26K mutation, A25T has a significantly higher likelihood than WT Cys C of alternative signal sequence cleavage after Ala20 ('site 1' or even earlier in the Cys C sequence. Overall, our results indicate that the A25T polymorphism does not cause a significant reduction in Cys C secretion, but instead predisposes the protein to be cleaved at an alternative signal sequence cleavage site if site 2 is hindered. Additional N-terminal amino acids resulting from alternative signal sequence cleavage may, in turn, affect the protease

  2. Influence of microenvironment pH, humidity, and temperature on the stability of polymorphic and amorphous forms of clopidogrel bisulfate

    DEFF Research Database (Denmark)

    Raijada, Dhara K; Singh, Saranjit; Bansal, Arvind K

    2010-01-01

    The effect of microenvironment pH, humidity, and temperature was evaluated on the stability of polymorphic and amorphous forms of clopidogrel bisulfate, when present alone or in combinations. Oxalic acid and sodium carbonate were used as solid stressors to create acidic and alkaline p...... more degradation than the individual forms above critical relative humidity (85% RH). Similar higher degradation was observed between 75% RH and 85% RH in case of acid-stressed samples. In alkaline microenvironment, all the samples showed identical decomposition attributed to conversion of bisulfate...

  3. Serotonin transporter gene-linked polymorphic region (5-HTTLPR) influences decision making under ambiguity and risk in a large Chinese sample.

    Science.gov (United States)

    He, Qinghua; Xue, Gui; Chen, Chuansheng; Lu, Zhonglin; Dong, Qi; Lei, Xuemei; Ding, Ni; Li, Jin; Li, He; Chen, Chunhui; Li, Jun; Moyzis, Robert K; Bechara, Antoine

    2010-11-01

    Risky decision making is a complex process that involves weighing the probabilities of alternative options that can be desirable, undesirable, or neutral. Individuals vary greatly in how they make decisions either under ambiguity and/or under risk. Such individual differences may have genetic bases. Based on previous studies on the genetic basis of decision making, two decision making tasks [i.e., the Iowa Gambling Task (IGT) and Loss Aversion Task (LAT)] were used to test the effect of 5-HTTLPR polymorphism on decision making under ambiguity and under risk in a large Han Chinese sample (572 college students, 312 females). Basic intelligence and memory tests were also included to control for the influence of basic cognitive abilities on decision making. We found that 5-HTTLPR polymorphism significantly influenced performance in both IGT and LAT. After controlling for intelligence and memory abilities, subjects homozygous for s allele had lower IGT scores than l carriers in the first 40 trials of the IGT task. They also exhibited higher loss aversion than l carriers in the LAT task. Moreover, the effects of 5-HTTLPR were stronger for males than for females. These results extend the literature on the important role of emotion in decision making under ambiguity and risk, and shed additional lights on how decision making is influenced by culture as well as sex differences. Combining our results with existing literature, we propose that these effects might be mediated by a neural circuitry that comprises the amygdala, ventromedial prefrontal cortex, and insular cortex. Understanding the genetic factors affecting decision making in healthy subjects may allow us to better identify at-risk individuals, and better target the development of new potential treatments for specific disorders such as schizophrenia, addiction, and depression. Copyright © 2010 Elsevier Ltd. All rights reserved.

  4. Serotonin Transporter Gene-Linked Polymorphic Region (5-HTTLPR) Influences Decision Making under Ambiguity and Risk in a Large Chinese Sample

    Science.gov (United States)

    He, Qinghua; Xue, Gui; Chen, Chuansheng; Lu, Zhonglin; Dong, Qi; Lei, Xuemei; Ding, Ni; Li, Jin; Li, He; Chen, Chunhui; Li, Jun; Moyzis, Robert K.; Bechara, Antoine

    2010-01-01

    Risky decision-making is a complex process that involves weighing the probabilities of alternative options that can be desirable, undesirable, or neutral. Individuals vary greatly in how they make decisions either under ambiguity and/or under risk. Such individual differences may have genetic bases. Based on previous studies on the genetic basis of decision making, two decision making tasks [i.e., Iowa Gambling Task (IGT) and Loss Aversion Task (LAT)] were used to test the effect of 5-HTTLPR polymorphism on decision making under ambiguity and under risk in a large Han Chinese sample (572 college students, 312 females). Basic intelligence and memory tests were also included to control for the influence of basic cognitive abilities on decision making. We found that 5-HTTLPR polymorphism significantly influenced performance in both IGT and LAT. After controlling for intellectual and memory abilities, subjects homozygous for s allele had lower IGT scores than l carriers in the first 40 trials of the IGT task. They also exhibited higher loss aversion than l carriers in the LAT task. Moreover, the effects of 5-HTTLPR were stronger for males than for females. These results extend the literature on the important role of emotion in decision under ambiguity and risk, and provide additional lights on how decision-making is influenced by culture as well as sex differences. Combining our results with existing literature, we propose that these effects might be mediated by a neural circuitry that comprises the amygdala, ventromedial prefrontal cortex, and insular cortex. Understanding the genetic factors affecting decision in healthy subjects may allow us better identify at-risk individuals, and target better the development of new potential treatments for specific disorders such as schizophrenia, addiction, and depression. PMID:20659488

  5. Epistasis between 5-HTTLPR and ADRA2B polymorphisms influences attentional bias for emotional information in healthy volunteers.

    Science.gov (United States)

    Naudts, Kris H; Azevedo, Ruben T; David, Anthony S; van Heeringen, Kees; Gibbs, Ayana A

    2012-09-01

    Individual differences in emotional processing are likely to contribute to vulnerability and resilience to emotional disorders such as depression and anxiety. Genetic variation is known to contribute to these differences but they remain incompletely understood. The serotonin transporter (5-HTTLPR) and α2B-adrenergic autoreceptor (ADRA2B) insertion/deletion polymorphisms impact on two separate but interacting monaminergic signalling mechanisms that have been implicated in both emotional processing and emotional disorders. Recent studies suggest that the 5-HTTLPR s allele is associated with a negative attentional bias and an increased risk of emotional disorders. However, such complex behavioural traits are likely to exhibit polygenicity, including epistasis. This study examined the contribution of the 5-HTTLPR and ADRA2B insertion/deletion polymorphisms to attentional biases for aversive information in 94 healthy male volunteers and found evidence of a significant epistatic effect (pbias for aversive information was attenuated by possession of the ADRA2B deletion variant whereas in the absence of the s allele, the bias was enhanced. These data identify a cognitive mechanism linking genotype-dependent serotonergic and noradrenergic signalling that is likely to have implications for the development of cognitive markers for depression/anxiety as well as therapeutic drug effects and personalized approaches to treatment.

  6. C-reactive protein (+1444C>T) polymorphism influences CRP response following a moderate inflammatory stimulus.

    Science.gov (United States)

    D'Aiuto, Francesco; Casas, Juan P; Shah, Tina; Humphries, Steve E; Hingorani, Aroon D; Tonetti, Maurizio S

    2005-04-01

    Elevations in C-reactive protein (CRP) concentration are associated with an increased risk of future coronary events in prospective studies and it has been suggested that CRP could be used to aid risk prediction. A +1444C>T polymorphism in the CRP gene has been associated with differences in CRP concentration. We investigated the effect of this polymorphism on the CRP response to periodontal therapy, an intermediate inflammatory stimulus. Clinical parameters, CRP, and interleukin-6 (IL-6) concentrations were evaluated in 55 consecutive patients suffering from periodontitis at baseline, 1, 7 and 30 days after an intensive course of periodontal treatment. In a multivariate analysis individuals homozygous for the +1444T allele showed higher CRP concentrations (day 1, 21.10+/-4.81 mg/L and day 7, 4.89+/-0.74 mg/L) compared with C-allele carriers (day 1, 12.37+/-1.61 mg/L and day 7, 3.08+/-2.00 mg/L). This effect was independent of conventional cardiovascular risk factors and inflammatory factors known to affect CRP concentrations. CRP genotype may need to be considered when CRP values are used in coronary risk prediction.

  7. Gene-environment interaction: Does fluoride influence the reproductive hormones in male farmers modified by ERα gene polymorphisms?

    Science.gov (United States)

    Ma, Qiang; Huang, Hui; Sun, Long; Zhou, Tong; Zhu, Jingyuan; Cheng, Xuemin; Duan, Lijv; Li, Zhiyuan; Cui, Liuxin; Ba, Yue

    2017-12-01

    The occurrence of endemic fluorosis is derived from high fluoride levels in drinking water and industrial fumes or dust. Reproductive disruption is also a major harm caused by fluoride exposure besides dental and skeletal lesions. However, few studies focus on the mechanism of fluoride exposure on male reproductive function, especially the possible interaction of fluoride exposure and gene polymorphism on male reproductive hormones. Therefore, we conducted a cross-sectional study in rural areas of Henan province in China to explore the interaction between the estrogen receptor alpha (ERα) gene and fluoride exposure on reproductive hormone levels in male farmers living in the endemic fluorosis villages. The results showed that fluoride exposure significantly increased the serum level of estradiol in the hypothalamic-pituitary-testicular (HPT) axis in male farmers. Moreover, the observations indicated that fluoride exposure and genetic markers had an interaction on serum concentration of follicle-stimulating hormone and estradiol, and the interaction among different loci of the ERα gene could impact the serum testosterone level. Findings in the present work suggest that chronic fluoride exposure in drinking water could modulate the levels of reproductive hormones in males living in endemic fluorosis areas, and the interaction between fluoride exposure and ERα polymorphisms might affect the serum levels of hormones in the HPT axis in male farmers. Copyright © 2017 Elsevier Ltd. All rights reserved.

  8. Polymorphisms in CTLA4 influence incidence of drug-induced liver injury after renal transplantation in Chinese recipients.

    Directory of Open Access Journals (Sweden)

    Yifeng Guo

    Full Text Available Genetic polymorphisms in cytotoxic T lymphocyte-associated antigen 4 (CTLA4 play an influential role in graft rejection and the long-term clinical outcome of organ transplantation. We investigated the association of 5 CTLA4 single-nucleotide polymorphisms (SNPs (rs733618 C/T, rs4553808 A/G, rs5742909 C/T, rs231775 A/G, and rs3087243 G/A with drug-induced liver injury (DILI in Chinese renal transplantation (RT recipients. Each recipient underwent a 24-month follow-up observation for drug-induced liver damage. The CTLA4 SNPs were genotyped in 864 renal transplantation recipients. A significant association was found between the rs231775 genotype and an early onset of DILI in the recipients. Multivariate analyses revealed that a risk factor, recipient rs231775 genotype (p = 0.040, was associated with DILI. Five haplotypes were estimated for 4 SNPs (excluding rs733618; the frequency of haplotype ACGG was significantly higher in the DILI group (68.9% than in the non-DILI group (61.1% (p = 0.041. In conclusion, CTLA4 haplotype ACGG was partially associated with the development of DILI in Chinese kidney transplant recipients. The rs231775 GG genotype may be a risk factor for immunosuppressive drug-induced liver damage.

  9. The influence of TAP1 and TAP2 gene polymorphisms on TAP function and its inhibition by viral immune evasion proteins.

    Science.gov (United States)

    Praest, P; Luteijn, R D; Brak-Boer, I G J; Lanfermeijer, J; Hoelen, H; Ijgosse, L; Costa, A I; Gorham, R D; Lebbink, R J; Wiertz, E J H J

    2018-06-04

    Herpesviruses encode numerous immune evasion molecules that interfere with the immune system, particularly with certain stages in the MHC class I antigen presentation pathway. In this pathway, the transporter associated with antigen processing (TAP) is a frequent target of viral immune evasion strategies. This ER-resident transporter is composed of the proteins TAP1 and TAP2, and plays a crucial role in the loading of viral peptides onto MHC class I molecules. Several variants of TAP1 and TAP2 occur in the human population, some of which are linked to autoimmune disorders and susceptibility to infections. Here, we assessed the influence of naturally occurring TAP variants on peptide transport and MHC class I expression. In addition, we tested the inhibitory capacity of three viral immune evasion proteins, the TAP inhibitors US6 from human cytomegalovirus, ICP47 from herpes simplex virus type 1 and BNLF2a from Epstein-Barr virus, for a series of TAP1 and TAP2 variants. Our results suggest that these TAP polymorphisms have no or limited effect on peptide transport or MHC class I expression. Furthermore, our study indicates that the herpesvirus-encoded TAP inhibitors target a broad spectrum of TAP variants; inhibition of TAP is not affected by the naturally occurring polymorphisms of TAP tested in this study. Our findings suggest that the long-term coevolution of herpesviruses and their host did not result in selection of inhibitor-resistant TAP variants in the human population. Copyright © 2018. Published by Elsevier Ltd.

  10. A novel TaqI polymorphism in the coding region of the ovine TNXB gene in the MHC class III region: morphostructural and physiological influences.

    Science.gov (United States)

    Ajayi, Oyeyemi O; Adefenwa, Mufliat A; Agaviezor, Brilliant O; Ikeobi, Christian O N; Wheto, Matthew; Okpeku, Moses; Amusan, Samuel A; Yakubu, Abdulmojeed; De Donato, Marcos; Peters, Sunday O; Imumorin, Ikhide G

    2014-02-01

    The tenascin-XB (TNXB) gene has antiadhesive effects, functions in matrix maturation in connective tissues, and localizes to the major histocompatibility complex class III region. We hypothesized that it may influence adaptive physiological response through an effect on blood vessel function. We identified a novel g.1324 A→G polymorphism at a TaqI recognition site in a 454 bp fragment of ovine TNXB and genotyped it in 150 Nigerian sheep using PCR-RFLP. The missense mutation changes glutamic acid (GAA) to glycine (GGA). Among SNP genotypes, significant differences (P bone length. Interaction effects of breed, SNP genotype, and geographic location had a significant effect (P < 0.05) on chest girth. The SNP genotype was significantly (P < 0.05) associated with physiological traits of pulse rate and skin temperature. The observed effect of this novel polymorphism may be mediated through its role in connective tissue biology, requiring further association and functional studies.

  11. The influence of KIR gene presence/absence polymorphisms on the development of periodontal disease in smokers and non-smokers.

    Science.gov (United States)

    Mazurek-Mochol, Małgorzata; Majorczyk, Edyta; Banach, Jadwiga; Dembowska, Elżbieta; Kuśnierczyk, Piotr; Safranow, Krzysztof; Pawlik, Andrzej

    2017-01-01

    Periodontal diseases are highly prevalent inflammatory, multifactorial diseases. Smoking is one of the most important environmental risk factors for the development and severity of periodontal disease. Killer cell immunoglobulin-like receptors (KIRs) are members of the immunoglobulin (Ig) superfamily and play an essential role in the regulation of NK cell activity, allowing natural killer (NK) cells to sense and respond to human leukocyte antigen (HLA) class I. The aim of this study was to evaluate the influence of KIR gene presence/absence polymorphisms on the development of periodontal disease in smokers and non-smokers. This study enrolled 400 Caucasian subjects (age range 25-69 years) from the West Pomeranian region of Poland. The subjects were categorized into four subgroups (smoking and non-smoking patients with periodontal disease; smoking and non-smoking subjects without periodontal disease - control subjects). The differences of KIR gene frequencies between non-smoking patients and non-smoking control subjects as well as smoking patients and control subjects were not statistically significant. In multivariate regression analysis advanced age of patients and smoking were independent factors associated with increased frequency of periodontal disease. The results of this study suggest that the main factor associated with increased risk of periodontal disease is smoking, whereas KIR presence/absence polymorphism is not a significant factor involved in the pathogenesis of periodontal disease.

  12. Supplementation with Watermelon Extract Reduces Total Cholesterol and LDL Cholesterol in Adults with Dyslipidemia under the Influence of the MTHFR C677T Polymorphism.

    Science.gov (United States)

    Massa, Nayara M L; Silva, Alexandre S; de Oliveira, Caio V C; Costa, Maria J C; Persuhn, Darlene C; Barbosa, Carlos V S; Gonçalves, Maria da C R

    2016-08-01

    Dyslipidemia and genetic polymorphisms are associated with increased risk for developing cardiovascular diseases, and watermelon appears to have the potential to improve hyperlipidemia due to the presence of nutrients such as arginine and citrulline. To test the hypolipidemic effect of watermelon extract (Citrullus lanatus) and the influence of the methylenetetrahydrofolate reductase genotype (MTHFR C677T) on supplementation response. This is an experimental clinical phase II randomized and double-blind study. Forty-three subjects with dyslipidemia were randomly divided into 2 groups: experimental (n = 22) and control (n = 21) groups. The subjects were supplemented daily for 42 days with 6 g of watermelon extract or a mixture of carbohydrates (sucrose/glucose/fructose). The use of watermelon extract reduced plasma total cholesterol (p watermelon extract in reducing plasma levels of lipids in humans. The MTHFR C677T polymorphism did not affect the plasma lipid concentration but made individuals more responsive to treatment with watermelon. The consumption of this functional food represents an alternative therapy in the combined treatment of patients with dyslipidemia, promoting health and minimizing the development of risk factors for cardiovascular diseases.

  13. Outcome after BCG treatment for urinary bladder cancer may be influenced by polymorphisms in the NOS2 and NOS3 genes.

    Science.gov (United States)

    Ryk, Charlotta; Koskela, Lotta Renström; Thiel, Tomas; Wiklund, N Peter; Steineck, Gunnar; Schumacher, Martin C; de Verdier, Petra J

    2015-12-01

    Bacillus Calmette-Guérin (BCG)-treatment is an established treatment for bladder cancer, but its mechanisms of action are not fully understood. High-risk non-muscle invasive bladder-cancer (NMIBC)-patients failing to respond to BCG-treatment have worse prognosis than those undergoing immediate radical cystectomy and identification of patients at risk for BCG-failure is of high priority. Several studies indicate a role for nitric oxide (NO) in the cytotoxic effect that BCG exerts on bladder cancer cells. In this study we investigated whether NO-synthase (NOS)-gene polymorphisms, NOS2-promoter microsatellite (CCTTT)n, and the NOS3-polymorphisms-786T>C (rs2070744) and Glu298Asp (rs1799983), can serve as possible molecular markers for outcome after BCG-treatment for NMIBC. All NMIBC-patients from a well-characterized population based cohort were analyzed (n=88). Polymorphism data were combined with information from 15-years of clinical follow-up. The effect of BCG-treatment on cancer-specific death (CSD), recurrence and progression in patients with varying NOS-genotypes were studied using Cox proportional hazard-models and log rank tests. BCG-treatment resulted in significantly better survival in patients without (Log rank: p=0.006; HR: 0.12, p=0.048), but not in patients with a long version ((CCTTT)n ≧13 repeats) of the NOS2-promoter microsatellite. The NOS3-rs2070744(TT) and rs1799983(GG)-genotypes showed decreased risk for CSD (Log rank(TT): p=0.001; Log rank(GG): p=0.010, HR(GG): 0.16, p=0.030) and progression (Log rank(TT): p<0.001, HR(TT): 0.05, p=0.005; Log rank(GG): p<0.001, HR(GG): 0.10, p=0.003) after BCG-therapy compared to the other genotypes. There was also a reduction in recurrence in BCG-treated patients that was mostly genotype independent. Analysis of combined genotypes identified a subgroup of 30% of the BCG-treated patients that did not benefit from BCG-treatment. Our results suggest that the investigated polymorphisms influence patient response

  14. Acute Normal Tissue Reactions in Head-and-Neck Cancer Patients Treated With IMRT: Influence of Dose and Association With Genetic Polymorphisms in DNA DSB Repair Genes

    International Nuclear Information System (INIS)

    Werbrouck, Joke; Ruyck, Kim de; Duprez, Frederic; Veldeman, Liv; Claes, Kathleen; Eijkeren, Marc van; Boterberg, Tom; Willems, Petra; Vral, Anne; Neve, Wilfried de; Thierens, Hubert

    2009-01-01

    Purpose: To investigate the association between dose-related parameters and polymorphisms in DNA DSB repair genes XRCC3 (c.-1843A>G, c.562-14A>G, c.722C>T), Rad51 (c.-3429G>C, c.-3392G>T), Lig4 (c.26C>T, c.1704T>C), Ku70 (c.-1310C>G), and Ku80 (c.2110-2408G>A) and the occurrence of acute reactions after radiotherapy. Materials and Methods: The study population consisted of 88 intensity-modulated radiation therapy (IMRT)-treated head-and-neck cancer patients. Mucositis, dermatitis, and dysphagia were scored using the Common Terminology Criteria (CTC) for Adverse Events v.3.0 scale. The population was divided into a CTC0-2 and CTC3+ group for the analysis of each acute effect. The influence of the dose on critical structures was analyzed using dose-volume histograms. Genotypes were determined by polymerase chain reaction (PCR) combined with restriction fragment length polymorphism or PCR-single base extension assays. Results: The mean dose (D mean ) to the oral cavity and constrictor pharyngeus (PC) muscles was significantly associated with the development of mucositis and dysphagia, respectively. These parameters were considered confounding factors in the radiogenomics analyses. The XRCC3c.722CT/TT and Ku70c.-1310CG/GG genotypes were significantly associated with the development of severe dysphagia (CTC3+). No association was found between the investigated polymorphisms and the development of mucositis or dermatitis. A risk analysis model for severe dysphagia, which was developed based on the XRCC3c.722CT/TT and Ku70c.-1310CG/GG genotypes and the PC dose, showed a sensitivity of 78.6% and a specificity of 77.6%. Conclusions: The XRCC3c.722C>T and Ku70c.-1310C>G polymorphisms as well as the D mean to the PC muscles were highly associated with the development of severe dysphagia after IMRT. The prediction model developed using these parameters showed a high sensitivity and specificity

  15. Influence of VEGFA gene polymorphisms rs2010963 and rs699947 on clinical and laboratory indicators in diabetic retinopathy among patients with type 2 diabetes mellitus

    Directory of Open Access Journals (Sweden)

    A.S. Gudz

    2017-10-01

    Full Text Available Background. A key factor of neoangiogenesis deve­lopment in diabetic retinopathy (DR among patients with type 2 diabetes mellitus (DM is vascular endothelial growth factor A (VEGFA. The important role of genetic polymorphisms of the VEGFA gene indicates a number of studies and meta-analyzes, that have shown their association with DR, especially with its proliferative variant, which varies in different populations. Accordingly, the purpose of this work was to find out the influence of the polymorphic genotypes rs2010963 and rs699947 of the VEGFA gene on clinical and laboratory parameters of DR in DM patients from Ukrainian population. Materials and methods. The study involved 302 patients with type 2 diabetes mellitus and DR. Diagnosis was established according to the international clinical classification adopted by the American Academy of Ophthalmology (2003. The control group consisted of 98 people who did not have DM and DR, as well as other ophthalmic diseases. All patients were operated on cataract. In the intraocular fluid collected during the surgery, the VEGFA content was determined by the immunoassay method. Analysis of the polymorphic DNA loci of the VEGFA gene: rs2010963 and rs699947 was performed in a real time polymerase chain reaction using TaqMan Mutation Detection Assays (Thermo Fisher Scientific, USA. Results. An analysis of the study results showed that rs2010963 polymorphism had an effect on the intraocular fluid VEGFA level (maximum — under the C/C risk genotype. This polymorphism was related to the sex (the genotype C/C was more common in men than in women: 3 : 1, the presence of proliferative DR (most often was determined by the presence of the genotype C/C: 45.4 % and neovascularization of the optic disc (most often determined by the pre­sence of heterozygotes G/C: 21.4 %. Polymorphism rs699947 had an effect on the visual acuity (the minimum was available in the genotype C/C, the thickness of the retina (the maximum

  16. The influence of high intensity exercise and the Val66Met polymorphism on circulating BDNF and locomotor learning.

    Science.gov (United States)

    Helm, Erin E; Matt, Kathleen S; Kirschner, Kenneth F; Pohlig, Ryan T; Kohl, Dave; Reisman, Darcy S

    2017-10-01

    Brain-derived neurotrophic factor (BDNF) has been directly related to exercise-enhanced motor performance in the neurologically injured animal model; however literature concerning the role of BDNF in the enhancement of motor learning in the human population is limited. Previous studies in healthy subjects have examined the relationship between intensity of an acute bout of exercise, increases in peripheral BDNF and motor learning of a simple isometric upper extremity task. The current study examined the role of high intensity exercise on upregulation of peripheral BDNF levels as well as the role of high intensity exercise in mediation of motor learning and retention of a novel locomotor task in neurologically intact adults. In addition, the impact of a single nucleotide polymorphism in the BDNF gene (Val66Met) in moderating the relationship between exercise and motor learning was explored. It was hypothesized that participation in high intensity exercise prior to practicing a novel walking task (split-belt treadmill walking) would elicit increases in peripheral BDNF as well as promote an increased rate and magnitude of within session learning and retention on a second day of exposure to the walking task. Within session learning and retention would be moderated by the presence or absence of Val66Met polymorphism. Fifty-four neurologically intact participants participated in two sessions of split-belt treadmill walking. Step length and limb phase were measured to assess learning of spatial and temporal parameters of walking. Serum BDNF was collected prior to and immediately following either high intensity exercise or 5min of quiet rest. The results demonstrated that high intensity exercise provides limited additional benefit to learning of a novel locomotor pattern in neurologically intact adults, despite increases in circulating BDNF. In addition, presence of a single nucleotide polymorphism on the BDNF gene did not moderate the magnitude of serum BDNF increases

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

    Directory of Open Access Journals (Sweden)

    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

  18. Influence of NR3C1 and VDR polymorphisms on stable warfarin dose in patients with mechanical cardiac valves.

    Science.gov (United States)

    Lee, Kyung Eun; Chung, Jee Eun; Yi, Boram; Cho, Yoon Jeong; Kim, Hyun Jeong; Lee, Gwan Yung; Kim, Joo Hee; Chang, Byung Chul; Gwak, Hye Sun

    2017-06-01

    The aim of this study was to evaluate the associations between polymorphisms of VKORC1, CYP2C9, CYP4F2, NR3C1 and VDR genes and stable warfarin doses in Korean patients with mechanical heart valves. Seventeen single-nucleotide polymorphisms (SNPs) in 204 patients with stable warfarin dose were analyzed: VKORC1 (rs9934438), CYP2C9 (rs1057910), CYP4F2 (rs2108622), NR3C1 (rs41423247, rs1800445, rs56149945, rs10052957, rs6198, rs33388, rs6196, and rs244465), and VDR (rs1544410, rs11568820, rs731236, rs757343, rs7975232, and rs2228570). Statistical analyses were conducted to evaluate the associations of gene variations with stable warfarin dose. Number needed to genotype was obtained by calculating the percentage of patients whose predicted dose was at least 20% higher or lower than the actual stable dose. The combined genotypes of rs7975232 and rs2228570 of the VDR gene revealed a significant association with stable warfarin dose, along with VKORC1, CYP2C9, and CYP4F2 polymorphisms. Patients with the genotype combination GT,TT/CT,CC of VDR rs7975232/rs2228570 required significantly higher stable warfarin dose (5.79±2.02mg) than those with the other genotypic combinations (5.19±1.78mg, p=0.034). Multivariate analysis showed that VDR rs7975232/rs2228570 explained 2.0% of the 47.5% variability in overall warfarin dose. Adding VDR SNP combinations to the base model including non-genetic variables (age, sex, and body weight) and genetic variables (VKORC1 rs9934438, CYP2C9 rs1057910, and CYP4F2 rs2108622) gave a number needed to genotype of 41. This study showed that stable warfarin dose is associated with VDR SNPs along with VKORC1, CYP2C9, and CYP4F2 SNPs. Copyright © 2017 Elsevier B.V. All rights reserved.

  19. 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.

  20. Influence of correlation between HLA-G polymorphism and Interleukin-6 (IL6) gene expression on the risk of schizophrenia.

    Science.gov (United States)

    Shivakumar, Venkataram; Debnath, Monojit; Venugopal, Deepthi; Rajasekaran, Ashwini; Kalmady, Sunil V; Subbanna, Manjula; Narayanaswamy, Janardhanan C; Amaresha, Anekal C; Venkatasubramanian, Ganesan

    2018-07-01

    Converging evidence suggests important implications of immuno-inflammatory pathway in the risk and progression of schizophrenia. Prenatal infection resulting in maternal immune activation and developmental neuroinflammation reportedly increases the risk of schizophrenia in the offspring by generating pro-inflammatory cytokines including IL-6. However, it is not known how prenatal infection can induce immuno-inflammatory responses despite the presence of immuno-inhibitory Human Leukocyte Antigen-G (HLA-G) molecules. To address this, the present study was aimed at examining the correlation between 14 bp Insertion/Deletion (INDEL) polymorphism of HLA-G and IL-6 gene expression in schizophrenia patients. The 14 bp INDEL polymorphism was studied by PCR amplification/direct sequencing and IL-6 gene expression was quantified by using real-time RT-PCR in 56 schizophrenia patients and 99 healthy controls. We observed significantly low IL6 gene expression in the peripheral mononuclear cells (PBMCs) of schizophrenia patients (t = 3.8, p = .004) compared to the controls. In addition, schizophrenia patients carrying Del/Del genotype of HLA-G 14 bp INDEL exhibited significantly lower IL6 gene expression (t = 3.1; p = .004) than the Del/Ins as well as Ins/Ins carriers. Our findings suggest that presence of "high-expressor" HLA-G 14 bp Del/Del genotype in schizophrenia patients could attenuate IL-6 mediated inflammation in schizophrenia. Based on these findings it can be assumed that HLA-G and cytokine interactions might play an important role in the immunological underpinnings of schizophrenia. Copyright © 2017 Elsevier Ltd. All rights reserved.

  1. Influence of music on steroid hormones and the relationship between receptor polymorphisms and musical ability: a pilot study.

    Science.gov (United States)

    Fukui, Hajime; Toyoshima, Kumiko

    2013-01-01

    Studies have shown that music confers plasticity to the brain. In a preliminary pilot study, we examined the effect of music listening on steroid hormones and the relationship between steroid hormone receptor polymorphisms and musical ability. Twenty-one subjects (10 males and 11 females) were recruited and divided into musically talented and control groups. The subjects selected (1) music they preferred (chill-inducing music) and (2) music they did not like. Before and after the experiments, saliva was collected to measure the levels of steroid hormones such as testosterone, estradiol, and cortisol. DNA was also isolated from the saliva samples to determine the androgen receptor (AR) and arginine vasopressin receptor 1A genotypes. Advanced Measures of Music Audiation (AMMA) was used to determine the musical ability of the subjects. With both types of music, the cortisol levels decreased significantly in both sexes. The testosterone (T) levels declined in males when they listened to both types of music. In females, the T levels increased in those listening to chill-inducing music but declined when they listened to music they disliked. However, these differences were not significant. The 17-beta estradiol levels increased in males with both types of music, whereas the levels increased with chill-inducing music but declined with disliked music in females. The AMMA scores were higher for the short repeat length-type AR than for the long repeat length-type. Comparisons of AR polymorphisms and T levels before the experiments showed that the T levels were within the low range in the short repeat length-type group and there was a positive relationship with the repeat length, although it was not significant. This is the first study conducted in humans to analyze the relationships between the AR gene, T levels, and musical ability.

  2. The influence of L-opsin gene polymorphisms and neural ageing on spatio-chromatic contrast sensitivity in 20-71 year olds.

    Science.gov (United States)

    Dees, Elise W; Gilson, Stuart J; Neitz, Maureen; Baraas, Rigmor C

    2015-11-01

    Chromatic contrast sensitivity may be a more sensitive measure of an individual's visual function than achromatic contrast sensitivity. Here, the first aim was to quantify individual- and age-related variations in chromatic contrast sensitivity to a range of spatial frequencies for stimuli along two complementary directions in color space. The second aim was to examine whether polymorphisms at specific amino acid residues of the L- and M-opsin genes (OPN1LW and OPN1MW) known to affect spectral tuning of the photoreceptors could influence spatio-chromatic contrast sensitivity. Chromatic contrast sensitivity functions were measured in 50 healthy individuals (20-71 years) employing a novel pseudo-isochromatic grating stimulus. The spatio-chromatic contrast sensitivity functions were found to be low pass for all subjects, independent of age and color vision. The results revealed a senescent decline in spatio-chromatic contrast sensitivity. There were considerable between-individual differences in sensitivity within each age decade for individuals 49 years old or younger, and age did not predict sensitivity for these age decades alone. Forty-six subjects (including a color deficient male and eight female carriers) were genotyped for L- and M-opsin genes. The Ser180Ala polymorphisms on the L-opsin gene were found to influence the subject's color discrimination and their sensitivity to spatio-chromatic patterns. The results expose the significant role of neural and genetic factors in the deterioration of visual function with increasing age. Copyright © 2015 Elsevier Ltd. All rights reserved.

  3. Neurological toxicity after phenytoin infusion in a pediatric patient with epilepsy: influence of CYP2C9, CYP2C19 and ABCB1 genetic polymorphisms.

    Science.gov (United States)

    Dorado, P; López-Torres, E; Peñas-Lledó, E M; Martínez-Antón, J; Llerena, A

    2013-08-01

    Pharmacogenetic studies have shown that genetic defects in drug-metabolizing enzymes encoded by CYP2C9, CYP2C19 genes and by the transporter ABCB1 gene can influence phenytoin (PTH) plasma levels and toxicity. The patient reported here is a 2-year-old girl with a medical history of cryptogenic (probably symptomatic) epilepsy, who had her first focal seizure with secondary generalization at 13 months of age. She initially received oral valproate treatment and three months later, she was prescribed an oral oxcarbazepine treatment. At 20 months of age, she was admitted to the Emergency Department because of generalized convulsive Status Epilepticus needing to be immediately treated with rectal diazepam (0.5 mg kg(-1)), intravenous diazepam (0.3 mg kg(-1)), and intravenous phenytoin with an initial-loading dose of 15 mg kg(-1). However, two hours after the initial-loading dose of PTH, the patient developed dizziness, nystagmus, ataxia and excessive sedation. Other potential causes of PTH toxicity were excluded such as drug interactions, decreased albumin or lab error. Therefore, to explain the neurological toxicity, PTH plasma levels and CYP2C9, CYP2C19 and ABCB1 genetic polymorphisms were analyzed. Initial plasma PTH levels were higher than expected (69 mg l(-1); normal range: 10-20 mg l(-1)), and the patient was homozygous for the CYP2C9*2 allele, heterozygous for the CYP2C19*4 allele and homozygous for the 3435C and 1236C ABCB1 alleles. Present findings support the previously established relationship between CYP2C9 and CYP2C19 genetic polymorphisms and the increased risk to develop PTH toxicity owing to high plasma concentrations. Nevertheless, although the association of these genes with PTH-induced adverse effects has been well-documented in adult populations, this is the first report examining the influence of these genetic polymorphisms on PTH plasma levels and toxicity in a pediatric patient.

  4. 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

    DEFF Research Database (Denmark)

    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...

  5. IkappaBalpha polymorphism at promoter region (rs2233408) influences the susceptibility of gastric cancer in Chinese.

    Science.gov (United States)

    Wang, Shiyan; Tian, Linwei; Zeng, Zhirong; Zhang, Mingdong; Wu, Kaichun; Chen, Minhu; Fan, Daiming; Hu, Pinjin; Sung, Joseph J Y; Yu, Jun

    2010-02-05

    Nuclear factor of kappa B inhibitor alpha (I kappaB alpha) protein is implicated in regulating a variety of cellular process from inflammation to tumorigenesis. The objective of this study was to investigate the susceptibility of rs2233408 T/C genotype in the promoter region of I kappaB alpha to gastric cancer and the association of this polymorphism with clinicopathologic variables in gastric cancer patients. A population-based case-control study was conducted between 1999 and 2006 in Guangdong Province, China. A total of 564 gastric cancer patients and 566 healthy controls were enrolled in this study. rs2233408 genotypes in I kappaB alpha were analyzed by TaqMan SNP genotyping assay. Both rs2233408 T homozygote (TT) and T heterozygotes (TC and TT) had significantly reduced gastric cancer risk (TT: OR = 0.250, 95% CI = 0.069-0.909, P = 0.035; TC and TT: OR = 0.721, 95% CI = 0.530-0.981, P = 0.037), compared with rs2233408 C homozygote (CC). rs2233408 T heterozygotes were significantly associated with reduced risk of intestinal-type gastric cancer with ORs of 0.648 (95% CI = 0.459-0.916, P = 0.014), but not with the diffuse or mix type of gastric cancer. The association between rs2233408 T heterozygotes and gastric cancer appeared more apparent in the older patients (age>40) (OR = 0.674, 95% CI = 0.484-0.939, P = 0.02). rs2233408 T heterozygotes was associated with non-cardiac gastric cancer (OR = 0.594, 95% CI = 0.411-0.859, P = 0.006), but not with cardiac gastric cancer. However, rs2233408 polymorphism was not associated with the prognosis of gastric cancer patients. I kappaB alpha rs2233408 T heterozygotes were associated with reduced risk of gastric cancer, especially for the development of certain subtypes of gastric cancer in Chinese population.

  6. IκBα polymorphism at promoter region (rs2233408 influences the susceptibility of gastric cancer in Chinese

    Directory of Open Access Journals (Sweden)

    Sung Joseph JY

    2010-02-01

    Full Text Available Abstract Background Nuclear factor of kappa B inhibitor alpha (IκBα protein is implicated in regulating a variety of cellular process from inflammation to tumorigenesis. The objective of this study was to investigate the susceptibility of rs2233408 T/C genotype in the promoter region of IκBα to gastric cancer and the association of this polymorphism with clinicopathologic variables in gastric cancer patients. Methods A population-based case-control study was conducted between 1999 and 2006 in Guangdong Province, China. A total of 564 gastric cancer patients and 566 healthy controls were enrolled in this study. rs2233408 genotypes in IκBα were analyzed by TaqMan SNP genotyping assay. Results Both rs2233408 T homozygote (TT and T heterozygotes (TC and TT had significantly reduced gastric cancer risk (TT: OR = 0.250, 95% CI = 0.069-0.909, P = 0.035; TC and TT: OR = 0.721, 95% CI = 0.530-0.981, P = 0.037, compared with rs2233408 C homozygote (CC. rs2233408 T heterozygotes were significantly associated with reduced risk of intestinal-type gastric cancer with ORs of 0.648 (95% CI = 0.459-0.916, P = 0.014, but not with the diffuse or mix type of gastric cancer. The association between rs2233408 T heterozygotes and gastric cancer appeared more apparent in the older patients (age>40 (OR = 0.674, 95% CI = 0.484-0.939, P = 0.02. rs2233408 T heterozygotes was associated with non-cardiac gastric cancer (OR = 0.594, 95% CI = 0.411-0.859, P = 0.006, but not with cardiac gastric cancer. However, rs2233408 polymorphism was not associated with the prognosis of gastric cancer patients. Conclusions IκBα rs2233408 T heterozygotes were associated with reduced risk of gastric cancer, especially for the development of certain subtypes of gastric cancer in Chinese population.

  7. Experiments on different materials (polyamide, stainless & galvanized steel) influencing geothermal CaCO3 scaling formation: Polymorphs & elemental incorporation

    Science.gov (United States)

    Wedenig, Michael; Dietzel, Martin; Boch, Ronny; Hippler, Dorothee

    2016-04-01

    Thermal water is increasingly used for heat and electric power production providing base-load capable renewable and virtually unlimited geothermal energy. Compared to other energy sources geothermal facilities are less harmful to the environment, i.e. chemically and visually. In order to promote the economic viability of these systems compared to other traditional and renewable energy sources, production hindering processes such as corrosion and scaling of components arising from the typically high salinity thermal waters have to be considered as important economic factors. In this context, using proper materials being in contact with the thermal water is crucial and a playground for further improvements. Aim of the study presented, are basic experiments and observations of scaling and corrosive effects from hydrothermal water interacting with different materials and surfaces (stainless steel, polyamide, galvanized steel) and in particular the nucleation and growth effects of these materials regarding the precipitation of solid carbonate phases. The incorporation of Mg, Sr and Ba cations into the carbonate scalings are investigated as environmental proxy. For this purpose, hydrothermal carbonate precipitating experiments were initialized by mixing NaHCO3 and Ca-Mg-Sr-Ba-chloride solutions at temperatures ranging from 40 to 80 °C in glass reactors hosting artificial substrates of the above mentioned materials. The experiments show a strong dependence of the precipitation behaviour of calcium carbonate polymorphs on the particular material being present. Stainless steel and polyamide seem to restrict aragonite formation, whereas galvanized steel supports aragonite nucleation. Vaterite formation is promoted by polyamide surfaces. Importantly, vaterite is more soluble (less stable) compared to the other anhydrous calcium carbonate polymorphs, i.e. vaterite can be more easily re-dissolved. Thus, the use of polyamide components might reduce the amount and durability of

  8. Brain-derived neurotrophic factor (BDNF) Val66Met polymorphism interacts with gender to influence cortisol responses to mental stress.

    Science.gov (United States)

    Jiang, Rong; Babyak, Michael A; Brummett, Beverly H; Siegler, Ilene C; Kuhn, Cynthia M; Williams, Redford B

    2017-05-01

    Brain-derived neurotrophic factor (BDNF) Val66Met polymorphism has been associated with cortisol responses to stress with gender differences reported, although the findings are not entirely consistent. To evaluate the role of Val66Met genotype and gender on cortisol responses to stress, we conducted a 45-min mental stress protocol including four tasks and four rest periods. Blood cortisol was collected for assay immediately before and after each task and rest period. A significant two-way interaction of Val66Met genotype×gender (P=0.022) was observed on the total area under the curve (AUC), a total cortisol response over time, such that the Val/Val genotype was associated with a larger cortisol response to stress as compared to the Met group in women but not in men. Further contrast analyses between the Val/Val and Met group for each stress task showed a similar increased cortisol pattern among women Val/Val genotype but not among men. The present findings indicate the gender differences in the effect of Val66Met genotype on the cortisol responses to stress protocol, and extend the evidence for the importance of gender and the role of Val66Met in the modulation of stress reactivity and subsequent depression prevalence. Further studies and the underlying mechanism need to be investigated, which may provide an insight for prevention, intervention, and treatment strategies that target those at high risk. Copyright © 2017 Elsevier Ltd. All rights reserved.

  9. Influence of genetic polymorphisms and mutations in the cardiac pathology of iron overload in thalassemia and sickle cell anemia patients: a retrospective study

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    Veronica Agrigento

    2012-11-01

    Full Text Available Cardiac disease in thalassemia is determined by the accumulation of iron in the tissue. Genetic factors could influence the severity and the rapidity of the modifications of the cardiac tissue. Mutations or polymorphisms of genes have already been described as being implicated in cardiac disease. In particular, we studied the polymorphisms C1091T in the Connexin 37 gene (CX 37, 4G -668 5G in the Plasminogen Activator Inhibitor-1 gene (PAI 1 and 5A-1171 6A in the Stromelysin-1 gene (SL in 193 randomly selected patients affected by hemoglobinopathies and 100 normal subjects randomly selected from the general population. A retrospective analysis based on history, clinical data and imaging studies was carried out to assess the presence and type of heart disease. The results of our study do not demonstrate a close association between polymorphism in these candidate genes and cardiac disease, and in particular with myocardial infarction in a cohort of Sicilian patients affected by hemoglobinopathies. 地中海贫血心脏病的关键诱因是组织中的铁沉积。遗传因子可能影响心脏组织修复的严重程度和速度。基因突变或基因多态性与心脏病有关。尤其是,我们研究了193名随机选择的血红蛋白病患者以及从普通人群中随机选择的100名正常受试者的连接蛋白37基因(CX37)的C1091T、纤溶酶原激活物抑制剂-1基因(PAI1)的4G -668 5G 和基质分解素-1基因(SL)的5A-1171 6A等多态性。根据病史、临床资料和影像研究进行回顾性分析,以评估心脏病的存在情况和类型。我们的研究结果并没有表明这些候选基因的多态性和心脏疾病之间存在密切联系,尤其是与一组西西里岛血红蛋白病患者的心肌梗塞存在密切联系。

  10. The c.-1639g>A polymorphism of the VKORC1 gene and his influence on the therapeutic response during oral anticoagulants use

    Directory of Open Access Journals (Sweden)

    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.

  11. Polymorphisms of the GR and HSD11B1 genes influence body mass index and weight gain during hormone replacement treatment in patients with Addison's disease.

    Science.gov (United States)

    Molnár, Ágnes; Kövesdi, Annamária; Szücs, Nikolette; Tóth, Miklós; Igaz, Péter; Rácz, Károly; Patócs, Attila

    2016-08-01

    Glucocorticoid substitution is essential in patients with chronic primary adrenocortical insufficiency (Addison's disease) and both over-treatment and inadequate dosage have deleterious effects. Individual sensitivity to glucocorticoids is partly genetically determined. To test the hypothesis whether the well-characterized SNPs of the GR and HSD11B1 genes may modulate the individual sensitivity to exogenous glucocorticoids and may influence clinical and/or laboratory parameters and the glucocorticoid substitution dosage in patients with Addison's disease. 68 patients with primary adrenocortical insufficiency were involved. Clinical and laboratory data, as well as the dosage of the hormone replacement therapy were collected. Peripheral blood DNA was isolated, and the GR and HSD11B1 SNPs were examined using allele-specific PCR or Taqman assay on Real Time PCR. The allele frequency of the GR N363S polymorphism was higher in patients compared to the control group and the disease appeared significantly earlier in patients harbouring the GR A3669G compared to noncarriers. These patients had higher ACTH level measured at the time of diagnosis. Homozygous BclI carriers had higher body mass index (BMI) and lower total hydrocortisone equivalent supplementation dose needed than heterozygous or noncarriers. The BMI and weight gain during hormone replacement therapy were also higher in carriers of the HSD11B1 rs4844880 treated with glucocorticoids other than dexamethasone. The BclI polymorphism of the GR gene and the rs4844880 of the HSD11B1 gene may contribute to weight gain and may affect the individual need of glucocorticoid substitution dose in these patients. © 2016 John Wiley & Sons Ltd.

  12. Analysis of the influence of the T393C polymorphism of the GNAS gene on the clinical expression of primary hyperparathyroidism.

    Science.gov (United States)

    Piedra, María; Berja, Ana; Ramos, Laura; García-Unzueta, María Teresa; Morán, Jesús Manuel; Ruiz, David; Amado, José Antonio

    2017-12-01

    The receptor of parathyroid hormone and parathyroid hormone-related-protein (PTH/PTHrp) is located in the cell membrane of target tissues - kidney and osteoblasts. It is a G protein-coupled-receptor whose G s α subunit is encoded by the GNAS gene. Our aim was to study whether the single nucleotide polymorphism (SNP) T393C of the GNAS gene is associated with renal stones, bone mineral density (BMD), or bone remodelling markers in primary hyperparathyroidism (PHPT). An analysis was made of clinical and biochemical parameters and densitometric values in three areas and their relationship with the T393C SNP of the GNAS gene in 261 patients with primary hyperparathyroidism and in 328 healthy controls. Genotyping was performed using the Custom Taqman ® SNP Genotyping assay. The genotype frequencies of GNAS T/C 393 were similar in the control and PHPT groups. No association was found between genotypes and clinical expression of PHPT (renal stones and bone fractures). A nonstatistically significant trend was seen to lower BMD in the lumbar spine, femoral neck, and total hip in both PHPT and control C homozygote subjects. Genetic susceptibility to PHPT related to the GNAS T393C polymorphism or a major influence in its development and clinical expression were found. A C allele-related susceptibility to lower BMD in trabecular bone in both PHPT and control subjects is not sufficient to suggest a more severe clinical expression of PHPT. This trend may be considered as a basis for further studies with larger sample sizes and complementary functional evaluation. Copyright © 2017 SEEN y SED. Publicado por Elsevier España, S.L.U. All rights reserved.

  13. Androgen receptor gene CAG repeat polymorphism independently influences recovery of male sexual function after testosterone replacement therapy in postsurgical hypogonadotropic hypogonadism.

    Science.gov (United States)

    Tirabassi, Giacomo; Delli Muti, Nicola; Corona, Giovanni; Maggi, Mario; Balercia, Giancarlo

    2014-05-01

    Few and contradictory studies have evaluated the possible influence of androgen receptor (AR) gene CAG repeat polymorphism on male sexual function. In this study we evaluated the role of AR gene CAG repeat polymorphism in the recovery of sexual function after testosterone replacement therapy (TRT) in men affected by postsurgical hypogonadotropic hypogonadism, a condition which is often associated with hypopituitarism and in which the sexual benefits of TRT must be distinguished from those of pituitary-function replacement therapies. Fifteen men affected by postsurgical hypogonadotropic hypogonadism were retrospectively assessed before and after TRT. Main outcome measures included sexual parameters as assessed by the International Index of Erectile Function questionnaire, levels of pituitary dependent hormones (total testosterone, free T3, free T4, cortisol, insulin-like growth factor-1 [IGF-1], prolactin), and results of genetic analysis (AR gene CAG repeat number). Plasma concentrations of free T3, free T4, cortisol, and prolactin did not vary significantly between the two phases, while testosterone and IGF-1 increased significantly after TRT. A significant improvement in all sexual parameters studied was found. The number of CAG triplets was negatively and significantly correlated with changes in all the sexual parameters, while opposite correlations were found between changes in sexual parameters and changes in testosterone levels; no correlation of change in IGF1 with change in sexual parameters was reported. On multiple linear regression analysis, after correction for changes in testosterone, nearly all the associations between the number of CAG triplets and changes in sexual parameters were confirmed. Shorter length AR gene CAG repeat number is associated with the recovery of sexual function after TRT in postsurgical male hypogonadotropic hypogonadism, independently of the effects of concomitant pituitary-replacement therapies. © 2014 International Society

  14. Influence of interleukin-1 beta gene polymorphisms on the risk of myocardial infarction and ischemic stroke at young age in vivo and in vitro.

    Science.gov (United States)

    Yang, Bo; Zhao, Hua; X, Bin; Wang, Ya-Bin; Zhang, Jian; Cao, Yu-Kang; Wu, Qing; Cao, Feng

    2015-01-01

    In this study, by using vivo and vitro model, we assessed whether interleukin (IL)-1beta gene polymorphisms influence on the risk of myocardial infarction and ischemic stroke at young age. 147 patients (age stroke were deeded as control group and greed to give blood samples for DNA analysis and biochemical measurements by written informed consent. IL-1β-511 wild type (WT, CC) and SNP (TT) were established and transfected into Rat myocardial H9c2 cell and Mouse brain endothelial bEND.3 cells. In Young Age MI or stroke patients, the IL-1β levels of patients with 511CC are higher than that of patients with 511TT. In our study, NF-κB miRNA, iNOS activity, NF-κB, iNOS and Bax protein expressions of MI-induced H9c2 cell or stroke-induced bEND.3 cells in IL-1β-511TT group were lower than those of IL-1β-511CC. Additionally, the protein expression of MMP-2 of MI-induced H9c2 cell or stroke-induced bEND.3 cells in IL-1β-511TT group were higher than that of IL-1β 511CC group. In conclusion, our data indicate that IL-1β-511TT/CC influence on the risk of myocardial infarction and ischemic stroke at young age through NF-κB, iNOS, MMP-2 and Bax.

  15. Polymorphisms of genes related to the hypothalamic-pituitary-adrenal axis influence the cortisol awakening response as well as self-perceived stress.

    Science.gov (United States)

    Li-Tempel, Ting; Larra, Mauro F; Winnikes, Ulrike; Tempel, Tobias; DeRijk, Roel H; Schulz, André; Schächinger, Hartmut; Meyer, Jobst; Schote, Andrea B

    2016-09-01

    The hypothalamus-pituitary-adrenal (HPA) axis is a crucial endocrine system for coping with stress. A reliable and stable marker for the basal state of that system is the cortisol awakening response (CAR). We examined the influence of variants of four relevant candidate genes; the mineralocorticoid receptor gene (MR), the glucocorticoid receptor gene (GR), the serotonin transporter gene (5-HTT) and the gene encoding the brain-derived neurotrophic factor (BDNF) on CAR and self-perceived stress in 217 healthy subjects. We found that polymorphisms of GR influenced both, the basal state of the HPA axis as well as self-perceived stress. MR only associated with self-perceived stress and 5-HTT only with CAR. BDNF did not affected any of the investigated indices. In summary, we suggest that GR variants together with the CAR and supplemented with self reports on perceived stress might be useful indicators for the basal HPA axis activity. Copyright © 2016 Elsevier B.V. All rights reserved.

  16. The influence of heavy metals on the polymorphs of dicalcium silicate in the belite-rich clinkers produced from electroplating sludge.

    Science.gov (United States)

    Chen, Ying-Liang; Shih, Pai-Haung; Chiang, Li-Choung; Chang, Yi-Kuo; Lu, Hsing-Cheng; Chang, Juu-En

    2009-10-15

    The purpose of this study is to utilize an electroplating sludge for belite-rich clinker production and to observe the influence of heavy metals on the polymorphs of dicalcium silicate (C(2)S). Belite-rich clinkers prepared with 0.5-2% of NiO, ZnO, CuO, and Cr(2)O(3) were used to investigate the individual effects of the heavy metals in question. The Reference Intensity Ratio (RIR) method was employed to determine the weight fractions of gamma-C(2)S and beta-C(2)S in the clinkers, and their microstructures were examined by the transmission electron microscopy (TEM). The results showed that nickel, zinc, and chromium have positive effects on beta-C(2)S stabilization (Cr(3+)>Ni(2+)>Zn(2+)), whereas copper has a negative effect. The addition of up to 10% electroplating sludge did not have any negative influence on the formation of C(2)S. It was observed that gamma-C(2)S decreased while beta-C(2)S increased with a rise in the addition of the electroplating sludge. Moreover, nickel and chromium mainly contributed to stabilizing beta-C(2)S in the belite-rich clinkers produced from the electroplating sludge.

  17. Fatty acid CoA ligase-4 gene polymorphism influences fatty acid metabolism in metabolic syndrome, but not in depression.

    Science.gov (United States)

    Zeman, Miroslav; Vecka, Marek; Jáchymová, Marie; Jirák, Roman; Tvrzická, Eva; Stanková, Barbora; Zák, Ales

    2009-04-01

    The composition of polyunsaturated fatty acids (PUFAs) in cell membranes and body tissues is altered in metabolic syndrome (MetS) and depressive disorder (DD). Within the cell, fatty acid coenzyme A (CoA) ligases (FACLs) activate PUFAs by esterifying with CoA. The FACL4 isoform prefers PUFAs (arachidonic and eicosapentaenoic acid) as substrates, and the FACL4 gene is mapped to Xq23. We have analyzed the association between the common single nucleotide polymorphism (SNP) (rs1324805, C to T substitution) in the first intron of the FACL4 gene and MetS or DD. The study included 113 healthy subjects (54 Males/59 Females), 56 MetS patients (34M/22F) and 41 DD patients (7M/34F). In MetS group, T-carriers and patients with CC or C0 (CC/C0) genotype did not differ in the values of metabolic indices of MetS and M/F ratio. Nevertheless, in comparison with CC/C0, the T-allele carriers were characterized by enhanced unfavorable changes in fatty acid metabolism typical for MetS: higher content of dihomogammalinolenic acid (P phosphatidylcholine (PC) (P = 0.052), lower index of Delta5 desaturation (P insulin, conjugated dienes and index of insulin resistance, but showed no significant association with the studied SNP. The present study shows that the common SNP (C to T substitution) in the first intron of the FACL4 gene is associated with altered FA composition of plasma phosphatidylcholines in patients with MetS.

  18. An NFKB1 promoter insertion/deletion polymorphism influences risk and outcome in acute respiratory distress syndrome among Caucasians.

    Directory of Open Access Journals (Sweden)

    Ednan K Bajwa

    2011-05-01

    Full Text Available Nuclear factor-κB (NF-κB is required for transcription of many pro-inflammatory genes and has been implicated in the pathogenesis of acute respiratory distress syndrome (ARDS. We hypothesized that a known functional polymorphism in the promoter of the NFKB1 gene may affect susceptibility to and outcome from ARDS.A case control study was conducted among a cohort of patients admitted to the intensive care unit (ICU with risk factors for the development of ARDS. 379 patients with ARDS and 793 at-risk controls were studied. Patients were followed for 60 days with development of ARDS as a primary outcome; ARDS-related mortality and organ dysfunction were secondary outcomes.Patients homozygous for the 4 base pair deletion in the promoter of NFKB1 (del/del did not have an increased odds ratio (OR of developing ARDS in unadjusted analysis but were more likely to develop ARDS in the presence of a significant interaction between the del/del genotype and age (OR 5.21, 95% CI 1.35-20.0. In multivariate analysis, patients with ARDS and the del/del genotype also had increased 60 day mortality (HR 1.54, 95% CI 1.01-2.36 and more severe daily organ dysfunction (P<.001 when compared to ARDS patients with other genotypes.The del/del genotype is associated with an age-dependent increase in odds of developing ARDS. Patients with the del/del genotype and ARDS also have increased hazard of 60 day mortality and more organ failure.

  19. Polymorphisms in the dopamine receptor 2 gene region influence improvements during working memory training in children and adolescents.

    Science.gov (United States)

    Söderqvist, Stina; Matsson, Hans; Peyrard-Janvid, Myriam; Kere, Juha; Klingberg, Torkel

    2014-01-01

    Studying the effects of cognitive training can lead to finding better treatments, but it can also be a tool for investigating factors important for brain plasticity and acquisition of cognitive skills. In this study, we investigated how single-nucleotide polymorphisms (SNPs) and ratings of intrinsic motivation were associated to interindividual differences in improvement during working memory training. The study included 256 children aged 7-19 years who were genotyped for 13 SNPs within or near eight candidate genes previously implicated in learning: COMT, SLC6A3 (DAT1), DRD4, DRD2, PPP1R1B (DARPP32), MAOA, LMX1A, and BDNF. Ratings on the intrinsic motivation inventory were also available for 156 of these children. All participants performed at least 20 sessions of working memory training, and performance during the training was logged and used as the outcome variable. We found that two SNPs, rs1800497 and rs2283265, located near and within the dopamine receptor 2 (DRD2) gene, respectively, were significantly associated with improvements during training (p motivation did not correlate with training outcome. However, we observed both the main effect of genotype at those two loci as well as the interaction between genotypes and ratings of intrinsic motivation (perceived competence). Both SNPs have previously been shown to affect DRD2 receptor density primarily in the BG. Our results suggest that genetic variation is accounting for some interindividual differences in how children acquire cognitive skills and that part of this effect is also seen on intrinsic motivation. Moreover, they suggest that dopamine D2 transmission in the BG is a key factor for cognitive plasticity.

  20. Sex influences eQTL effects of SLE and Sjögren's syndrome-associated genetic polymorphisms.

    Science.gov (United States)

    Lindén, Magdalena; Ramírez Sepúlveda, Jorge I; James, Tojo; Thorlacius, Gudny Ella; Brauner, Susanna; Gómez-Cabrero, David; Olsson, Tomas; Kockum, Ingrid; Wahren-Herlenius, Marie

    2017-10-25

    Systemic lupus erythematosus (SLE) and primary Sjögren's syndrome (pSS) are autoimmune disorders characterized by autoantibodies, dysregulated B cells, and notably high female-to-male incidence ratios. Genome-wide association studies have identified several susceptibility SNPs for both diseases. Many SNPs in the genome are expression quantitative trait loci (eQTLs), with context-dependent effects. Assuming that sex is a biological context, we investigated whether SLE/pSS SNPs act as eQTLs in B cells and used a disease-targeted approach to understand if they display sex-specific effects. We used genome-wide genotype and gene expression data from primary B cells from 125 males and 162 females. The MatrixEQTL R package was used to identify eQTLs within a genomic window of 2 Mb centered on each of 22 established SLE and/or pSS susceptibility SNPs. To find sex-specific eQTLs, we used a linear model with a SNP * sex interaction term. We found ten SNPs affecting the expression of 16 different genes (FDR rs7574865-INPP1, rs7574865-MYO1B, rs4938573-CD3D, rs11755393-SNRPC, and rs4963128-PHRF1 were novel observations for the immune compartment and B cells. By analyzing the SNP * sex interaction terms, we identified six genes with differentially regulated expression in females compared to males, depending on the genotype of SLE/pSS-associated SNPs: SLC39A8 (BANK1 locus), CD74 (TNIP1 locus), PXK, CTSB (BLK/FAM167A locus), ARCN1 (CXCR5 locus), and DHX9 (NCF2 locus). We identified several unknown sex-specific eQTL effects of SLE/pSS-associated genetic polymorphisms and provide novel insight into how gene-sex interactions may contribute to the sex bias in systemic autoimmune diseases.

  1. Influence of Angiotensin-Converting-Enzyme Gene Polymorphism on Echocardiographic Data of Patients with Ischemic Heart Failure.

    Science.gov (United States)

    Duque, Gustavo Salgado; Silva, Dayse Aparecida da; Albuquerque, Felipe Neves de; Schneider, Roberta Siuffo; Gimenez, Alinne; Pozzan, Roberto; Rocha, Ricardo Mourilhe; Albuquerque, Denilson Campos de

    2016-11-01

    Association between angiotensin-converting-enzyme (ACE) gene polymorphisms and different clinical and echocardiographic outcomes has been described in patients with heart failure (HF) and coronary artery disease. Studying the genetic profile of the local population with both diseases is necessary to assess the occurrence of that association. To assess the frequency of ACE gene polymorphisms in patients with ischemic HF in a Rio de Janeiro population, as well as its association with echocardiographic findings. Genetic assessment of I/D ACE polymorphism in association with clinical, laboratory and echocardiographic analysis of 99 patients. The allele frequency was: 53 I alleles, and 145 D alleles. Genotype frequencies were: 49.5% DD; 47.48% DI; 3.02% II. Drug treatment was optimized: 98% on beta-blockers, and 84.8% on ACE inhibitors or angiotensin-receptor blocker. Echocardiographic findings: difference between left ventricular diastolic diameters (ΔLVDD) during follow-up: 2.98±8.94 (DD) vs. 0.68±8.12 (DI) vs. -11.0±7.00 (II), p=0.018; worsening during follow-up of the LV systolic diameter (LVSD): 65.3% DD vs. 19.0% DI vs. 0.0% II, p=0.01; of the LV diastolic diameter (LVDD): 65.3% DD vs. 46.8% DI vs. 0.0% II, p=0.03; and of the LV ejection fraction (LVEF): 67.3% DD vs. 40.4% DI vs. 33.3% II, p=0.024. Correlated with D allele: ΔLVEF, ΔLVSD, ΔLVDD. More DD genotype patients had worsening of the LVEF, LVSD and LVDD, followed by DI genotype patients, while II genotype patients had the best outcome. The same pattern was observed for ΔLVDD. Associação entre polimorfismos genéticos da enzima conversora da angiotensina (ECA) e diferentes evoluções clínicas e ecocardiográficas foi descrita em pacientes com insuficiência cardíaca (IC) e coronariopatia. O estudo do perfil genético da população local com as duas doenças torna-se necessário para verificar a ocorrência dessa associação. Avaliar a frequência dos polimorfismos genéticos da ECA em

  2. Using Single-nucleotide Polymorphisms and Genetic Mapping to find Candidate Genes that Influence Varroa-Specific Hygiene

    Science.gov (United States)

    Varroa-sensitive hygienic (VSH) behavior is one of two behaviors identified that are most important for controlling the growth of Varroa mite populations in bee hives. A study was conducted to map quantitative trait loci (QTL) that influence VSH so that resistance genes could be identified. Crosses ...

  3. The influence of NSAIDs on coumarin sensitivity in patients with CYP2C9 polymorphism after total hip replacement surgery.

    NARCIS (Netherlands)

    Beinema, M.J.; Jong, P.H. de; Salden, H.J.; Wijnen, M.H.W.A.; Meer, J.W.M. van der; Brouwers, J.R.B.J.

    2007-01-01

    OBJECTIVE: To determine the influence of NSAIDs on the international normalized ratio (INR) in patients with cytochrome P450 (CYP)-2C9 enzyme variants starting acenocoumarol (an oral coumarin) therapy during the first 7 days after total hip replacement surgery. METHODS: In this prospective study, an

  4. The influence of NSAIDs on coumarin sensitivity in patients with CYP2C9 polymorphism after total hip replacement surgery

    NARCIS (Netherlands)

    Beinema, Maarten J.; de Jong, Petra H.; Salden, Har J. M.; van Wijnen, Merel; van der Meer, Jan; Brouwers, Jacobus R. B. J.

    2007-01-01

    Objective: To determine the influence of NSAIDs on the international normalized ratio (INR) in patients with cytochrome P450 (CYP)-2C9 enzyme variants starting acenocoumarol (an oral coumarin) therapy during the first 7 days after total hip replacement surgery. Methods: In this prospective study, an

  5. Influence of chemotherapeutic drug-related gene polymorphisms on toxicity and survival of early breast cancer patients receiving adjuvant chemotherapy.

    Science.gov (United States)

    Ludovini, Vienna; Antognelli, Cinzia; Rulli, Antonio; Foglietta, Jennifer; Pistola, Lorenza; Eliana, Rulli; Floriani, Irene; Nocentini, Giuseppe; Tofanetti, Francesca Romana; Piattoni, Simonetta; Minenza, Elisa; Talesa, Vincenzo Nicola; Sidoni, Angelo; Tonato, Maurizio; Crinò, Lucio; Gori, Stefania

    2017-07-26

    We investigated whether GSTT1 ("null" allele), GSTM1 ("null"allele), GSTP1 (A313G), RFC1 (G80A), MTHFR (C677T), TS (2R/3R) polymorphisms were associated with toxicity and survival in patients with early breast cancer (EBC) treated with adjuvant chemotherapy (CT). This prospective trial included patients with stage I-III BC subjected to CT with CMF or FEC regimens. PCR-RFLP was performed for MTHFR, RFC1 and GSTP1, while PCR for TS, GSTT1 and GSTM1 genes. Among the 244 patients consecutively enrolled, 48.7% were treated with FEC and 51.3% with CMF. Patients with TS2R/3R genotype showed less frequently severe neutropenia (G3/G4) than those with TS2R/2R and 3R/3R genotype (p = 0.038). Patients with MTHFRCT genotype had a higher probability of developing severe neutropenia than those with MTHFR CC genotype (p = 0.043). Patients with RFC1GG or GSTT1-null genotype or their combination (GSTT1-null/RFC1GG) were significantly associated with a shorter disease free survival (DFS) (p = 0.009, p = 0.053, p = 0.003, respectively) and overall survival (OS) (p = 0.036, p = 0.015, p = 0.005, respectively). Multivariate analysis confirmed the association of RFC1GG genotype with a shorter DFS (p = 0.018) and of GSTT1-null genotype of a worse OS (p = 0.003), as well as for the combined genotypes GSTT1-null/RFC1GG, (DFS: p = 0.004 and OS: p = 0.003). Our data suggest that TS2R/2R and 3R/3R or MTHFR CT genotypes have a potential role in identifying patients with greater risk of toxicity to CMF/FEC and that RFC1 GG and GSTT1-null genotypes alone or in combination could be important markers in predicting clinical outcome in EBC patients.

  6. Chemokine MCP1/CCL2 and RANTES/CCL5 gene polymorphisms influence Henoch–Schönlein purpura susceptibility and severity

    Directory of Open Access Journals (Sweden)

    Hsin-Hui Yu

    2015-04-01

    Conclusion: Our results support the fact that chemokines play important roles in the pathogenesis of HSP. MCP1/CCL2 gene polymorphisms were associated with susceptibility for HSP. RANTES/CCL5 gene polymorphisms may be related to disease severity and HSP nephritis.

  7. A polymorphism in the IGF-I gene influences the age-related decline in circulating total IGF-I levels

    NARCIS (Netherlands)

    I. Rietveld (Ingrid); J.A.M.J.L. Janssen (Joseph); A. Hofman (Albert); C.M. van Duijn (Cornelia); S.W.J. Lamberts (Steven); H.A.P. Pols (Huib)

    2003-01-01

    markdownabstractOBJECTIVE: Recent studies have demonstrated an association between a 192 bp polymorphism of the IGF-I gene and total IGF-I serum levels, birth weight, body height and the risk of developing diabetes and cardiovascular diseases later on in life. This IGF-I gene polymorphism in the

  8. Polymorphism of the FTO Gene Influences Body Weight in Children with Type 1 Diabetes without Severe Obesity

    OpenAIRE

    Łuczyński, Włodzimierz; Fendler, Wojciech; Ramatowska, Anna; Szypowska, Agnieszka; Szadkowska, Agnieszka; Młynarski, Wojciech; Chumiecki, Miron; Jarosz-Chobot, Przemysława; Chrzanowska, Joanna; Noczyńska, Anna; Brandt, Agnieszka; Myśliwiec, Małgorzata; Głowińska-Olszewska, Barbara; Bernatowicz, Paweł; Kowalczuk, Oksana

    2014-01-01

    The objective was to compare the impact of clinical and genetic factors on body mass index (BMI) in children with type 1 diabetes (T1DM) without severe obesity. A total of 1,119 children with T1DM (aged 4–18 years) were qualified to take part in the study. All children were genotyped for variants of FTO, MC4R, INSIG2, FASN, NPC1, PTER, SIRT1, MAF, IRT1, and CD36. Results. Variants of FTO showed significant association with BMI-SDS in the T1DM group. The main factors influencing BMI-SDS in chi...

  9. No influence of the polymorphisms CYP2C19 and CYP2D6 on the efficacy of cyclophosphamide, thalidomide, and bortezomib in patients with Multiple Myeloma

    International Nuclear Information System (INIS)

    Vangsted, Annette J; Rasmussen, Henrik B; Søeby, Karen; Klausen, Tobias W; Abildgaard, Niels; Andersen, Niels F; Gimsing, Peter; Gregersen, Henrik; Vogel, Ulla; Werge, Thomas

    2010-01-01

    The response to treatment varies among patients with multiple myeloma and markers for prediction of treatment outcome are highly needed. Bioactivation of cyclophosphamide and thalidomide, and biodegradation of bortezomib, is dependent on cytochrome P450 metabolism. We explored the potential influence of different polymorphisms in the CYP enzymes on the outcome of treatment. Data was analyzed from 348 patients undergoing high-dose treatment and stem cell support in Denmark in 1994 to 2004. Clinical information on relapse treatment in 243 individual patients was collected. The patients were genotyped for the non-functional alleles CYP2C19*2 and CYP2D6*3, *4, *5 (gene deletion), *6, and CYP2D6 gene duplication. In patients who were treated with bortezomib and were carriers of one or two defective CYP2D6 alleles there was a trend towards a better time-to-next treatment. We found no association between the number of functional CYP2C19 and CYP2D6 alleles and outcome of treatment with cyclophosphamide or thalidomide. Neither was the number of functional CYP2C19 and CYP2D6 alleles associated with neurological adverse reactions to thalidomide and bortezomib. There was no association between functional CYP2C19 and CYP2D6 alleles and treatment outcome in multiple myeloma patients treated with cyclophosphamide, thalidomide or bortezomib. A larger number of patients treated with bortezomib are needed to determine the role of CYP2D6 alleles in treatment outcome

  10. The influence of lysozyme on mannitol polymorphism in freeze-dried and spray-dried formulations depends on the selection of the drying process.

    Science.gov (United States)

    Grohganz, Holger; Lee, Yan-Ying; Rantanen, Jukka; Yang, Mingshi

    2013-04-15

    Freeze-drying and spray-drying are often applied drying techniques for biopharmaceutical formulations. The formation of different solid forms upon drying is often dependent on the complex interplay between excipient selection and process parameters. The purpose of this study was to investigate the influence of the chosen drying method on the solid state form. Mannitol-lysozyme solutions of 20mg/mL, with the amount of lysozyme varying between 2.5% and 50% (w/w) of total solid content, were freeze-dried and spray-dried, respectively. The resulting solid state of mannitol was analysed by near-infrared spectroscopy in combination with multivariate analysis and further, results were verified with X-ray powder diffraction. It was seen that the prevalence of the mannitol polymorphic form shifted from β-mannitol to δ-mannitol with increasing protein concentration in freeze-dried formulations. In spray-dried formulations an increase in protein concentration resulted in a shift from β-mannitol to α-mannitol. An increase in final drying temperature of the freeze-drying process towards the temperature of the spray-drying process did not lead to significant changes. It can thus be concluded that it is the drying process in itself, rather than the temperature, that leads to the observed solid state changes. Copyright © 2013 Elsevier B.V. All rights reserved.

  11. Polymorphic Contracts

    Science.gov (United States)

    Belo, João Filipe; Greenberg, Michael; Igarashi, Atsushi; Pierce, Benjamin C.

    Manifest contracts track precise properties by refining types with predicates - e.g., {x : Int |x > 0 } denotes the positive integers. Contracts and polymorphism make a natural combination: programmers can give strong contracts to abstract types, precisely stating pre- and post-conditions while hiding implementation details - for example, an abstract type of stacks might specify that the pop operation has input type {x :α Stack |not ( empty x )} . We formalize this combination by defining FH, a polymorphic calculus with manifest contracts, and establishing fundamental properties including type soundness and relational parametricity. Our development relies on a significant technical improvement over earlier presentations of contracts: instead of introducing a denotational model to break a problematic circularity between typing, subtyping, and evaluation, we develop the metatheory of contracts in a completely syntactic fashion, omitting subtyping from the core system and recovering it post facto as a derived property.

  12. Influence of FTO rs9939609 polymorphism on appetite, ghrelin, leptin, IL6, TNFα levels, and food intake of women with morbid obesity.

    Science.gov (United States)

    Magno, Fernanda Cristina Carvalho Mattos; Guaraná, Helena Chrispim; Fonseca, Ana Carolina Proença; Cabello, Giselda Maria Kalil; Carneiro, João Régis Ivar; Pedrosa, Aline Pereira; Ximenes, Ana Carolina; Rosado, Eliane Lopes

    2018-01-01

    The fat mass and obesity-related ( FTO ) gene has a strong relationship with obesity, extreme obesity and inflammatory state, and may also be associated with food intake regulation. The aim of the present study was to evaluate the influence of the rs9939609 single-nucleotide polymorphism of the FTO gene on appetite, ghrelin, leptin, interleukin 6 (IL6), tumor necrosis factor α (TNFα) levels and food intake of morbidly obese women. The study comprised 70 women, aged between 20 and 48 years, from Rio de Janeiro, Brazil. The participants were selected according to the body mass index between 40 and 60 kg/m 2 . Anthropometric and biochemical data were measured during fasting. Hormones and inflammatory data were measured before and after the participants ate an isocaloric meal. Dietary records were calculated and analyzed using a nutritional assessment program. Visual analog scales were used for behaviors of the sensations of appetite and food preferences. The FTO rs9939609 variant was genotyped using real-time polymerase chain reaction. Participants with the AA genotype had lower values of ghrelin and IL6 and higher values of leptin than those with TT and TA in the postprandial period. Comparing the plasma concentrations of ghrelin, insulin, IL6 and TNFα intragenotypes, it was observed that those with TT had decreased leptin and increased IL6 at the postprandial period. Subjects with TA showed increased postprandial IL6, and those with AA had decreased postprandial ghrelin. There was no difference in TNFα intra- and intergenotypes. The postprandial sensations of hunger were lower in AA than those with TT. There were differences between genotypes regarding ingested grams of protein by weight, cholesterol, B3, B5, B6 and B12 vitamins, and selenium potassium and sodium minerals. These findings suggest that genetics may exert an influence on physiologic factors and might alter eating behavior.

  13. Influence of Polymorphisms in the HTR3A and HTR3B Genes on Experimental Pain and the Effect of the 5-HT3 Antagonist Granisetron.

    Directory of Open Access Journals (Sweden)

    Sofia Louca Jounger

    Full Text Available The aim of this study was to investigate experimentally if 5-HT3 single nucleotide polymorphisms (SNP contribute to pain perception and efficacy of the 5-HT3-antagonist granisetron and sex differences. Sixty healthy participants were genotyped regarding HTR3A (rs1062613 and HTR3B (rs1176744. First, pain was induced by bilateral hypertonic saline injections (HS, 5.5%, 0.2 mL into the masseter muscles. Thirty min later the masseter muscle on one side was pretreated with 0.5 mL granisetron (1 mg/mL and on the other side with 0.5 mL placebo (isotonic saline followed by another HS injection (0.2 mL. Pain intensity, pain duration, pain area and pressure pain thresholds (PPTs were assessed after each injection. HS evoked moderate pain, with higher intensity in the women (P = 0.023, but had no effect on PPTs. None of the SNPs influenced any pain variable in general, but compared to men, the pain area was larger in women carrying the C/C (HTR3A (P = 0.015 and pain intensity higher in women with the A/C alleles (HTR3B (P = 0.019. Pre-treatment with granisetron reduced pain intensity, duration and area to a lesser degree in women (P < 0.05, but the SNPs did not in general influence the efficacy of granisetron. Women carrying the C/T & T/T (HTR3A genotype had less reduction of pain intensity (P = 0.041 and area (P = 0.005, and women with the C/C genotype (HTR3B had less reduction of pain intensity (P = 0.030, duration (P = 0.030 and area compared to men (P = 0.017. In conclusion, SNPs did not influence experimental muscle pain or the effect of granisetron on pain variables in general, but there were some sex differences in pain variables that seem to be influenced by genotypes. However, due to the small sample size further research is needed before any firm conclusions can be drawn.

  14. gene polymorphism and its serum lev

    Indian Academy of Sciences (India)

    Navya

    Association of Interleukin-10 (-1082 A>G, -819 C >T and -592 C >A) gene polymorphism and its ... Th2 induced component of anti-β cell immunity is mediated principally by IL-10 (Lee et al. ..... promoter polymorphisms influence the clinical outcome of diffuse large B-cell lymphoma. ... Bone Marrow Transplant 36, 1089-1095.

  15. Influence of Polymorphisms in the HTR3A and HTR3B Genes on Experimental Pain and the Effect of the 5-HT3 Antagonist Granisetron.

    Science.gov (United States)

    Louca Jounger, Sofia; Christidis, Nikolaos; Hedenberg-Magnusson, Britt; List, Thomas; Svensson, Peter; Schalling, Martin; Ernberg, Malin

    2016-01-01

    The aim of this study was to investigate experimentally if 5-HT3 single nucleotide polymorphisms (SNP) contribute to pain perception and efficacy of the 5-HT3-antagonist granisetron and sex differences. Sixty healthy participants were genotyped regarding HTR3A (rs1062613) and HTR3B (rs1176744). First, pain was induced by bilateral hypertonic saline injections (HS, 5.5%, 0.2 mL) into the masseter muscles. Thirty min later the masseter muscle on one side was pretreated with 0.5 mL granisetron (1 mg/mL) and on the other side with 0.5 mL placebo (isotonic saline) followed by another HS injection (0.2 mL). Pain intensity, pain duration, pain area and pressure pain thresholds (PPTs) were assessed after each injection. HS evoked moderate pain, with higher intensity in the women (P = 0.023), but had no effect on PPTs. None of the SNPs influenced any pain variable in general, but compared to men, the pain area was larger in women carrying the C/C (HTR3A) (P = 0.015) and pain intensity higher in women with the A/C alleles (HTR3B) (P = 0.019). Pre-treatment with granisetron reduced pain intensity, duration and area to a lesser degree in women (P granisetron. Women carrying the C/T & T/T (HTR3A) genotype had less reduction of pain intensity (P = 0.041) and area (P = 0.005), and women with the C/C genotype (HTR3B) had less reduction of pain intensity (P = 0.030), duration (P = 0.030) and area compared to men (P = 0.017). In conclusion, SNPs did not influence experimental muscle pain or the effect of granisetron on pain variables in general, but there were some sex differences in pain variables that seem to be influenced by genotypes. However, due to the small sample size further research is needed before any firm conclusions can be drawn.

  16. Influence of SNP Polymorphisms in DNA Repair Genes on the Level of Persistent Damage in Human Lymphocytes After Exposure to 2 Gy of Ionising Radiation

    International Nuclear Information System (INIS)

    Milic, M.; Rozgaj, R.; Kasuba, V.; Kubelka, D.; Angelini, S.; Hrelia, P.

    2011-01-01

    Variation in cell response to ionising radiation could be result of changes in gene expression and/or polymorphisms of DNA repair genes. The aim of the study was to estimate the DNA damage level in human lymphocytes after exposure to 2 Gy of ionising radiation. Medical workers occupationally exposed to low doses of ionising radiation (N = 20) and matched controls (N 20) were genotyped for polymorphic hOGG1, XRCC1, APE1, XPD10, XPD23, XRCC3, PARP1 and MGMT genes. Micronucleus (MN) test was used for the estimation of DNA damage before and after radiation. Incidence of MN in irradiated samples positively correlated with age and negatively with polymorphic variants of XPD23. Significant difference was observed between irradiated homozygotes (HO) and heterozygotes (HE). HO and HE APE1 differed in MN before exposure. HO and polymorphic variants of XPD10 differed in MN after exposure. Gender showed different MN in the exposed group after exposure. Age correlated positively with MN after exposure, working probation and received dose. Multiple regression analysis revealed connection between polymorphic variants of APE1 and XRCC3 with MN before exposure. These results confirm the value of micronucleus assay in DNA damage estimation and suggest possible use of polymorphic genes in monitoring of individuals professionaly exposed to ionising radiation. (author)

  17. Sulfamerazine: Understanding the Influence of Slip Planes in the Polymorphic Phase Transformation through X-Ray Crystallographic Studies and ab Initio Lattice Dynamics.

    Science.gov (United States)

    Pallipurath, Anuradha R; Skelton, Jonathan M; Warren, Mark R; Kamali, Naghmeh; McArdle, Patrick; Erxleben, Andrea

    2015-10-05

    Understanding the polymorphism exhibited by organic active-pharmaceutical ingredients (APIs), in particular the relationships between crystal structure and the thermodynamics of polymorph stability, is vital for the production of more stable drugs and better therapeutics, and for the economics of the pharmaceutical industry in general. In this article, we report a detailed study of the structure-property relationships among the polymorphs of the model API, Sulfamerazine. Detailed experimental characterization using synchrotron radiation is complemented by computational modeling of the lattice dynamics and mechanical properties, in order to study the origin of differences in millability and to investigate the thermodynamics of the phase equilibria. Good agreement is observed between the simulated phonon spectra and mid-infrared and Raman spectra. The presence of slip planes, which are found to give rise to low-frequency lattice vibrations, explains the higher millability of Form I compared to Form II. Energy/volume curves for the three polymorphs, together with the temperature dependence of the thermodynamic free energy computed from the phonon frequencies, explains why Form II converts to Form I at high temperature, whereas Form III is a rare polymorph that is difficult to isolate. The combined experimental and theoretical approach employed here should be generally applicable to the study of other systems that exhibit polymorphism.

  18. SLC2A3 single-nucleotide polymorphism and duplication influence cognitive processing and population-specific risk for attention-deficit/hyperactivity disorder.

    Science.gov (United States)

    Merker, Sören; Reif, Andreas; Ziegler, Georg C; Weber, Heike; Mayer, Ute; Ehlis, Ann-Christine; Conzelmann, Annette; Johansson, Stefan; Müller-Reible, Clemens; Nanda, Indrajit; Haaf, Thomas; Ullmann, Reinhard; Romanos, Marcel; Fallgatter, Andreas J; Pauli, Paul; Strekalova, Tatyana; Jansch, Charline; Vasquez, Alejandro Arias; Haavik, Jan; Ribasés, Marta; Ramos-Quiroga, Josep Antoni; Buitelaar, Jan K; Franke, Barbara; Lesch, Klaus-Peter

    2017-07-01

    Attention-deficit/hyperactivity disorder (ADHD) is a common, highly heritable neurodevelopmental disorder with profound cognitive, behavioral, and psychosocial impairments with persistence across the life cycle. Our initial genome-wide screening approach for copy number variants (CNVs) in ADHD implicated a duplication of SLC2A3, encoding glucose transporter-3 (GLUT3). GLUT3 plays a critical role in cerebral glucose metabolism, providing energy for the activity of neurons, which, in turn, moderates the excitatory-inhibitory balance impacting both brain development and activity-dependent neural plasticity. We therefore aimed to provide additional genetic and functional evidence for GLUT3 dysfunction in ADHD. Case-control association analyses of SLC2A3 single-nucleotide polymorphisms (SNPs) and CNVs were conducted in several European cohorts of patients with childhood and adult ADHD (SNP, n = 1,886 vs. 1,988; CNV, n = 1,692 vs. 1,721). These studies were complemented by SLC2A3 expression analyses in peripheral cells, functional EEG recordings during neurocognitive tasks, and ratings of food energy content. Meta-analysis of all cohorts detected an association of SNP rs12842 with ADHD. While CNV analysis detected a population-specific enrichment of SLC2A3 duplications only in German ADHD patients, the CNV + rs12842 haplotype influenced ADHD risk in both the German and Spanish cohorts. Duplication carriers displayed elevated SLC2A3 mRNA expression in peripheral blood cells and altered event-related potentials reflecting deficits in working memory and cognitive response control, both endophenotypic traits of ADHD, and an underestimation of energy units of high-caloric food. Taken together, our results indicate that both common and rare SLC2A3 variation impacting regulation of neuronal glucose utilization and energy homeostasis may result in neurocognitive deficits known to contribute to ADHD risk. © 2017 Association for Child and Adolescent Mental Health.

  19. Influence of tumour suppressor gene (TP53, BRCA1 and BRCA2) polymorphisms on polycystic ovary syndrome in South Indian women.

    Science.gov (United States)

    Siddamalla, Swapna; Reddy, Tumu Venkat; Govatati, Suresh; Guruvaiah, Praveen; Deenadayal, Mamata; Shivaji, Sisinthy; Bhanoori, Manjula

    2018-05-24

    Polycystic Ovary Syndrome (PCOS) is a heterogeneous multifactorial endocrine metabolic disorder. In addition to hyperandrogenism, acne, hirsutism, obesity, oligoanovulation and infertility, insulin resistance is also a common feature in women of PCOS. Tumor suppressor genes (TSGs) perform essential function in the maintenance of genomic stability and regulatory pathways influencing the activity of several replication and transcription factors. The main aim of this study was to investigate the association of Single Nucleotide Polymorphisms of TP53, BRCA1and BRCA2 genes with the susceptibility to PCOS in South Indian women. Present study investigated association between TP53 gene (rs1042522 G/C), BRCA1 (rs71361504 -/GTT, rs3092986 T/C) and BRCA2 (rs206118 A/G) and, SNPs and PCOS risk. Genotyping of TSGs was carried out on DNA from PCOS patients (n = 110) and controls (n = 130) of South Indian origin by polymerase chain reaction (PCR) and confirmed by sequencing analysis. The genotype frequency and allele distributions of cases and controls were analyzed using Fisher's exact test. Haplotype frequencies for multiple loci and the standardized disequilibrium coefficient (D') for pair wise linkage disequilibrium (LD) were assessed by Haploview Software. Significant increase in frequencies ofTP53 (rs1042522 G/C), BRCA1 (rs71361504 -/GTT, rs3092986 T/C) genotypes and alleles in patients compared to controls. In addition, the frequency of the C/T (P = 0.002) and A/C (P = 0.012) haplotype was also significantly elevated in patients. But BRCA2 (rs206118 A/G) did not show significant association with PCOS. The TP53 and BRCA1 may constitute an inheritable risk factor for PCOS in South Indian women. Copyright © 2018 Elsevier B.V. All rights reserved.

  20. Analysis of TLR polymorphisms in typhoid patients and ...

    African Journals Online (AJOL)

    Ilakkia Sivaji

    2016-01-20

    Jan 20, 2016 ... implicated the genetic variations (polymorphisms) in TLR genes to influence the host susceptibility to infectious diseases. However, the available literature on TLR polymorphism and susceptibility to typhoid fever is unclear. Aim: This study aimed to investigate the polymorphism of TLRs 1, 2, 4 and 5 in ...

  1. Influence of A-21T and C-262T genetic polymorphisms at the promoter region of the catalase (CAT) on gene expression.

    Science.gov (United States)

    Saify, Khyber; Saadat, Iraj; Saadat, Mostafa

    2016-09-01

    Catalase (CAT, OMIM: 115500) is one of the major antioxidant enzymes, which plays an important role in the clearance of reactive oxygen species. Three genetic polymorphisms of A-21T (rs7943316), C-262T (rs1001179), and C-844T (rs769214) in the promoter region of the CAT have been reported. It has been suggested that these polymorphisms may alter the recognition sites of transcriptional factors, therefore it might be concluded that these polymorphisms may alter the expression levels of the gene. The aim of the present study is to evaluate the associations between these genetic variations and the CAT mRNA levels in human peripheral blood cells. The present study consisted of 47 healthy students of Shiraz University (south-west Iran). Genotypes of the CAT polymorphisms were determined by PCR based method. The quantitative CAT mRNA expression levels were investigated using quantitative real-time PCR. Analysis of variance revealed significant differences between the study genotypes (For A-21T polymorphism: F = 7.45; df = 2, 44; P = 0.002; For C-262T polymorphism: F = 15.17; df = 2, 44; P CAT in the AC/TT, TC/TC, TC/TT, and TC/TC diplotypes significantly were higher than the mRNA levels in AC/AC diplotype. There was a significant difference between the study genotypes (F = 9.24; df = 5, 41; P CAT mRNA levels compared with the AC/AC diplotype. The present findings indicated that these polymorphisms were significantly associated with the gene expression.

  2. The 5-HT₁A receptor C(1019)G polymorphism influences the intravaginal ejaculation latency time in Dutch Caucasian men with lifelong premature ejaculation.

    Science.gov (United States)

    Janssen, Paddy K C; van Schaik, R; Zwinderman, Aeilko H; Olivier, Berend; Waldinger, Marcel D

    2014-06-01

    Lifelong premature ejaculation (LPE) is characterized by persistent intravaginal ejaculation latency times (IELTs) of less than 1 min, and has been postulated as a neurobiological dysfunction related to diminished serotonergic neurotransmission with 5-HT₁A receptor hyperfunction and 5-HT₂C hypofunction. To investigate the relationship between 5-HT₁A receptor gene (HTR₁A)-C(1019)G promoter polymorphism and IELT in men with LPE. This polymorphism is known to increase 5-HT1A receptor expression. A prospective study was conducted in 54 Dutch Caucasian men with LPE. Baseline IELT during coitus was assessed by stopwatch over a 1-month period. All men were genotyped for HTR₁A gene polymorphism. Allele frequencies and genotypes of C and G variants of HTR₁A polymorphism were determined. Association between CC, CG, and GG genotypes and the IELT in men with LPE were investigated. IELT measured by stopwatch, HTR₁A polymorphism. In this cohort of men with LPE, the geometric mean IELT was 23.8 s. Of the 54 men, the CC, CG and GG genotype frequency for the C(1019)G polymorphism of the 5-HT₁A gene was 33%, 43% and 24%, respectively. The geometric mean IELT for the CC, CG and GG genotypes were 14.5, 27.7 and 36.0 s, respectively (p=0.019). Compared to GG and CG genotypes, men with CC genotype had a 250% and 190% shorter ejaculation time, respectively. HTR₁A gene polymorphism is associated with the IELT in men with LPE. Men with CC genotype have shorter IELTs than men with GG and CG genotypes. Copyright © 2014 Elsevier Inc. All rights reserved.

  3. Influence of FTO rs9939609 polymorphism on appetite, ghrelin, leptin, IL6, TNFα levels, and food intake of women with morbid obesity

    Directory of Open Access Journals (Sweden)

    Magno FCCM

    2018-05-01

    Full Text Available Fernanda Cristina Carvalho Mattos Magno,1 Helena Chrispim Guaraná,1 Ana Carolina Proença Fonseca,2 Giselda Maria Kalil Cabello,2 João Régis Ivar Carneiro,3 Aline Pereira Pedrosa,1 Ana Carolina Ximenes,1 Eliane Lopes Rosado1 1Institute of Nutrition, Federal University of Rio de Janeiro, Rio de Janeiro, RJ, Brazil; 2Oswaldo Cruz Foundation (FIOCRUZ, Oswaldo Cruz Institute (IOC, Human Genetics Laboratory, Rio de Janeiro, RJ, Brazil; 3Federal University of Rio de Janeiro, University Hospital Clementino Fraga Filho, Service of Nutrology, Rio de Janeiro, RJ, Brazil Background: The fat mass and obesity-related (FTO gene has a strong relationship with obesity, extreme obesity and inflammatory state, and may also be associated with food intake regulation.Objective: The aim of the present study was to evaluate the influence of the rs9939609 single-nucleotide polymorphism of the FTO gene on appetite, ghrelin, leptin, interleukin 6 (IL6, tumor necrosis factor α (TNFα levels and food intake of morbidly obese women.Materials and methods: The study comprised 70 women, aged between 20 and 48 years, from Rio de Janeiro, Brazil. The participants were selected according to the body mass index between 40 and 60 kg/m2. Anthropometric and biochemical data were measured during fasting. Hormones and inflammatory data were measured before and after the participants ate an isocaloric meal. Dietary records were calculated and analyzed using a nutritional assessment program. Visual analog scales were used for behaviors of the sensations of appetite and food preferences. The FTO rs9939609 variant was genotyped using real-time polymerase chain reaction.Results: Participants with the AA genotype had lower values of ghrelin and IL6 and higher values of leptin than those with TT and TA in the postprandial period. Comparing the plasma concentrations of ghrelin, insulin, IL6 and TNFα intragenotypes, it was observed that those with TT had decreased leptin and increased IL6

  4. Influence of serum leptin levels and Q223R leptin receptor polymorphism on clinical characteristic of patients with rheumatoid arthritis from Western Mexico.

    Science.gov (United States)

    Angel-Chávez, Luis I; Ruelas-Cinco, Elizabeth; Hernández-Bello, Jorge; Castro, Elena; Vázquez-Villamar, Mirna; Parra-Rojas, Isela; Brennan-Bourdon, L Michele; Muñoz-Barrios, Salvador; Guerrero-Velázquez, Celia; Muñoz-Valle, José Francisco

    2018-04-01

    The aim of the present study was to evaluate the possible association between the Q223R Leptin receptor (LEPR) polymorphism (A>G; rs1137101) and leptin levels in patients with rheumatoid arthritis (RA) from Western Mexico. A cross-sectional study was performed with 70 RA patients and 74 controls subject (CS). Disease activity was evaluated using DAS28 score, the Q223R LEPR polymorphism was determined by the Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP) and serum leptin levels, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) and rheumatoid factor (RF) were quantified. RA patients had significant high serum leptin levels compared with CS; leptin levels correlated strongly with body composition measures, but not with inflammatory markers, disease evolution, and activity. The genotype and allele frequencies of the Q223R LEPR polymorphism were not associated with RA. Similarly, leptin levels did not differ between Q223R LEPR genotypes. The LEPR Q223R polymorphism was not associated with RA risk in patients from Mexican population, even though high levels of serum leptin were present and these could explain the low weight observed in RA patients when they were compared to control subjects. However, the serum leptin levels did not correlate with inflammatory markers, severity and disease evolution.

  5. Influence of genetic polymorphisms on the effect of high- and standard-dose clopidogrel after percutaneous coronary intervention: the GIFT (Genotype Information and Functional Testing) study.

    Science.gov (United States)

    Price, Matthew J; Murray, Sarah S; Angiolillo, Dominick J; Lillie, Elizabeth; Smith, Erin N; Tisch, Rebecca L; Schork, Nicholas J; Teirstein, Paul S; Topol, Eric J

    2012-05-29

    This study sought to evaluate the influence of single nucleotide polymorphisms (SNPs) on the pharmacodynamic effect of high- or standard-dose clopidogrel after percutaneous coronary intervention (PCI). There is a lack of prospective, multicenter data regarding the effect of different genetic variants on clopidogrel pharmacodynamics over time in patients undergoing PCI. The GRAVITAS (Gauging Responsiveness with A VerifyNow assay-Impact on Thrombosis And Safety) trial screened patients with platelet function testing after PCI and randomly assigned those with high on-treatment reactivity (OTR) to either high- or standard-dose clopidogrel; a cohort of patients without high OTR were also followed. DNA samples obtained from 1,028 patients were genotyped for 41 SNPs in 17 genes related to platelet reactivity. After adjusting for clinical characteristics, the associations between the SNPs and OTR using linear regression were evaluated. CYP2C19*2 was significantly associated with OTR at 12 to 24 h (R(2) = 0.07, p = 2.2 × 10(-15)), 30 days (R(2) = 0.10, p = 1.3 × 10(-7)), and 6 months after PCI (R(2) = 0.07, p = 1.9 × 10(-11)), whereas PON1, ABCB1 3435 C→T, and other candidate SNPs were not. Carriers of 1 and 2 reduced-function CYP2C19 alleles were significantly more likely to display persistently high OTR at 30 days and 6 months, irrespective of treatment assignment. The portion of the risk of persistently high OTR at 30 days attributable to reduced-function CYP2C19 allele carriage was 5.2% in the patients randomly assigned to high-dose clopidogrel. CYP2C19, but not PON1 or ABCB1, is a significant determinant of the pharmacodynamic effects of clopidogrel, both early and late after PCI. In patients with high OTR identified by platelet function testing, the CYP2C19 genotype provides limited incremental information regarding the risk of persistently high reactivity with clopidogrel 150-mg maintenance dosing. (Genotype Information and Functional Testing Study [GIFT]; NCT

  6. The maternal homocysteine pathway is influenced by riboflavin intake and MTHFR polymorphisms without affecting the risk of orofacial clefts in the offspring.

    NARCIS (Netherlands)

    Vujkovic, M.; Steegers, E.A.P.; Meurs, J. van; Yazdanpanah, N.; Rooij, I.A.L.M. van; Uitterlinden, A.G.; Steegers-Theunissen, R.P.M.

    2010-01-01

    BACKGROUND/OBJECTIVES: Riboflavin is a cofactor for the 5,10-methylenetetrahydrofolate reductase (MTHFR) enzyme involved in the homocysteine pathway. The aim of this study was to investigate the effects of maternal riboflavin intake and two MTHFR polymorphisms (677C>T; Ala222Val and 1298A>C;

  7. Influence of IL-1RN intron 2 variable number of tandem repeats (VNTR) polymorphism on the age at onset of neuropsychiatric symptoms in Wilson's disease.

    Science.gov (United States)

    Gromadzka, Grazyna; Członkowska, Anna

    2011-01-01

    ABSTRACT Wilson's disease (WND) is an autosomal recessive copper storage disease characterized with diverse clinical pictures with the hepatic and/or neuropsychiatric symptoms manifesting at variable age. On the basis of the existing knowledge on possible copper-proinflammatory cytokines interactions, we hypothesized that in WND hereditary, over-/underexpression of PC or anti-inflammatory cytokines may have an impact on the course of the disease. We analyzed the clinical manifestations of WND in relationship to polymorphisms within genes for interleukin-1 receptor antagonist (IL1RN intron 2 VNTR polymorphism), interleukin-1α (IL1A G4845T), IL-1β (IL1B C-511T), IL-6 (IL6 G-174C), and tumor necrosis factor (TNF G-308A) in a total sample of 332 patients. The IL1B C-511T and IL1RN VNTR polymorphisms had an impact on copper metabolism parameters. None of the studied gene polymorphisms had effect on the mode of WND manifestation (neuropsychiatric vs. hepatic). Carriership of the IL1RN *2 allele was related to earlier WND onset, especially among patients with neuropsychiatric form of the disease (median 27.5 vs. 32.0 years, p = .003). Because of the crucial modulatory role of IL1ra on IL-1α and IL-1β proinflammatory functions, IL1ra and its interactions may play a role in the pathogenesis of the neurodegenerative process in WND; our results need to be replicated, possibly in different ethnic groups.

  8. 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...

  9. A gene-gene interaction between polymorphisms in the OCT2 and MATE1 genes influences the renal clearance of metformin

    DEFF Research Database (Denmark)

    Hougaard Christensen, Mette Marie; Pedersen, Rasmus Steen; Stage, Tore Bjerregaard

    2013-01-01

    The aim of this study was to determine the association between the renal clearance (CL(renal)) of metformin in healthy Caucasian volunteers and the single-nucleotide polymorphism (SNP) c.808G>T (rs316019) in OCT2 as well as the relevance of the gene-gene interactions between this SNP and (a) the ...

  10. The influence of a single nucleotide polymorphism within CNDP1 on susceptibility to diabetic nephropathy in Japanese women with type 2 diabetes.

    Directory of Open Access Journals (Sweden)

    Mahiro Kurashige

    Full Text Available BACKGROUND: Several linkage analyses have mapped a susceptibility locus for diabetic nephropathy to chromosome 18q22-23, and polymorphisms within the carnosine dipeptidase 1 gene (CNDP1, located on 18q22.3, have been shown to be associated with diabetic nephropathy in European subjects with type 2 diabetes. However, the association of this locus with diabetic nephropathy has not been evaluated in the Japanese population. In this study, we examined the association of polymorphisms within the CNDP1/CNDP 2 locus with diabetic nephropathy in Japanese subjects with type 2 diabetes. METHODOLOGY/PRINCIPAL FINDINGS: We genotyped a leucine repeat polymorphism (D18S880 that is within CNDP1 along with 29 single nucleotide polymorphisms (SNPs in the CNDP1/CNDP2 locus for 2,740 Japanese subjects with type 2 diabetes (1,205 nephropathy cases with overt nephropathy or with end-stage renal disease [ESRD], and 1,535 controls with normoalbuminuria. The association of each polymorphism with diabetic nephropathy was analysed by performing logistic regression analysis. We did not observe any association between D18S880 and diabetic nephropathy in Japanese subjects with type 2 diabetes. None of the 29 SNPs within the CNDP1/CNDP2 locus were associated with diabetic nephropathy, but a subsequent sex-stratified analysis revealed that 1 SNP in CNDP1 was nominally associated with diabetic nephropathy in women (rs12604675-A; p = 0.005, odds ratio [OR] = 1.76, 95% confidence interval [CI], 1.19-2.61. Rs12604675 was associated with overt proteinuria (p = 0.002, OR = 2.18, 95% CI, 1.32-3.60, but not with ESRD in Japanese women with type 2 diabetes. CONCLUSIONS/SIGNIFICANCE: Rs12604675-A in CNDP1 may confer susceptibility to overt proteinuria in Japanese women with type 2 diabetes.

  11. The 5-HT2C receptor gene Cys23Ser polymorphism influences the intravaginal ejaculation latency time in Dutch Caucasian men with lifelong premature ejaculation

    Directory of Open Access Journals (Sweden)

    Paddy KC Janssen

    2014-08-01

    Full Text Available It has been postulated that the persistent short intravaginal ejaculation latency time (IELT of men with lifelong premature ejaculation (LPE is related to 5-hydroxytryptamine (HT2C receptor functioning. The aim of this study was to investigate the relationship of Cys23Ser 5-HT2C receptor gene polymorphism and the duration of IELT in men with LPE. Therefore, a prospective study was conducted in 64 Dutch Caucasian men with LPE. Baseline IELT during coitus was assessed by stopwatch over a 1-month period. All men were genotyped for Cys23Ser 5-HT2C receptor gene polymorphism. Allele frequencies and genotypes of Cys and Ser variants of 5-HT2C receptor gene polymorphism were determined. Association between Cys/Cys and Ser/Ser genotypes and the natural logarithm of the IELT in men with LPE were investigated. As a result, the geometric mean, median and natural mean IELT were 25.2, 27.0, 33.9 s, respectively. Of all men, 20.0%, 10.8%, 23.1% and 41.5% ejaculated within 10, 10-20, 20-30 and 30-60 s after vaginal penetration. Of the 64 men, the Cys/Cys and Ser/Ser genotype frequency for the Cys23Ser polymorphism of the 5-HT2C receptor gene was 81% and 19%, respectively. The geometric mean IELT of the wildtypes (Cys/Cys is significantly lower (22.6 s; 95% CI 18.3-27.8 s than in male homozygous mutants (Ser/Ser (40.4 s; 95% CI 20.3-80.4 s (P = 0.03. It is concluded that Cys23Ser 5-HT2C receptor gene polymorphism is associated with the IELT in men with LPE. Men with Cys/Cys genotype have shorter IELTs than men with Ser/Ser genotypes.

  12. The 5-HT2C receptor gene Cys23Ser polymorphism influences the intravaginal ejaculation latency time in Dutch Caucasian men with lifelong premature ejaculation.

    Science.gov (United States)

    Janssen, Paddy Kc; Schaik, Ron van; Olivier, Berend; Waldinger, Marcel D

    2014-01-01

    It has been postulated that the persistent short intravaginal ejaculation latency time (IELT) of men with lifelong premature ejaculation (LPE) is related to 5-hydroxytryptamine (HT)2C receptor functioning. The aim of this study was to investigate the relationship of Cys23Ser 5-HT2C receptor gene polymorphism and the duration of IELT in men with LPE. Therefore, a prospective study was conducted in 64 Dutch Caucasian men with LPE. Baseline IELT during coitus was assessed by stopwatch over a 1-month period. All men were genotyped for Cys23Ser 5-HT2C receptor gene polymorphism. Allele frequencies and genotypes of Cys and Ser variants of 5-HT2C receptor gene polymorphism were determined. Association between Cys/Cys and Ser/Ser genotypes and the natural logarithm of the IELT in men with LPE were investigated. As a result, the geometric mean, median and natural mean IELT were 25.2, 27.0, 33.9 s, respectively. Of all men, 20.0%, 10.8%, 23.1% and 41.5% ejaculated within 10, 10-20, 20-30 and 30-60 s after vaginal penetration. Of the 64 men, the Cys/Cys and Ser/Ser genotype frequency for the Cys23Ser polymorphism of the 5-HT2C receptor gene was 81% and 19%, respectively. The geometric mean IELT of the wildtypes (Cys/Cys) is significantly lower (22.6 s; 95% CI 18.3-27.8 s) than in male homozygous mutants (Ser/Ser) (40.4 s; 95% CI 20.3-80.4 s) (P = 0.03). It is concluded that Cys23Ser 5-HT2C receptor gene polymorphism is associated with the IELT in men with LPE. Men with Cys/Cys genotype have shorter IELTs than men with Ser/Ser genotypes.

  13. Association between frequency of chromosomal aberrations and cancer risk is not influenced by genetic polymorphisms in GSTM1 and GSTT1

    DEFF Research Database (Denmark)

    Rossi, Anna Maria; Hansteen, Inger-Lise; Skjelbred, Camilla Furu

    2009-01-01

    (OR(high) = 4.0, 95% CrI, 1.4-10.0), and the digestive tract (OR(high) = 2.8, 95% CrI, 1.2-5.8). CONCLUSIONS: Despite the small size of the study groups, our results substantiate the cancer risk predictivity of CA frequency, ruling against a strong modifying effect of GSTM1 and GSTT1 polymorphisms....

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

    Directory of Open Access Journals (Sweden)

    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.

  15. A polymorphism in the stearoyl-CoA desaturase gene promoter influences monounsaturated fatty acid content of Duroc × Iberian hams

    Energy Technology Data Exchange (ETDEWEB)

    Henriquez-Rodriguez, E.; Tor, M.; Pena, R.N.; Estany, J.

    2015-07-01

    Data on 74 dry-cured hams from Duroc × Iberian pigs were used to examine whether the tag polymorphism AY487830:g.2228T>C in the promoter region of the stearoyl-CoA desaturase [SCD] gene affect fat desaturation and monounsaturated fatty acid (MUFA) as previously described in purebred Duroc hams. Samples were taken from sliced trays of dry-cured hams marketed as Jamón Ibérico de cebo, which were randomly purchased from the same supplier in different stores of the same supermarket chain. Genomic DNA was isolated from each sample to genotype for SCD and gender. Also, a sample of two slices was used to determine fat content and fatty acid (FA) composition by gas chromatography. The effect of the genotype (TT and CT) and gender (barrows and gilts) was estimated under a Bayesian setting. Results showed that the SCD polymorphism was associated to fat composition but not to fat content, with TT hams showing increased C18:1n-7, C18:1n-9, C20:1n-9 and MUFA (probability between 0.92-0.98) and decreased C18:2n-6, C20:4n-6 and polyunsaturated FA (PUFA) (probability between 0.91-0.99) as compared to the CT. As a result, the TT hams had more MUFA (0.95%) and a higher MUFA/PUFA ratio (0.43) than the CT. Barrows had more saturated FA (SFA) and less PUFA than gilts. No differences in MUFA content were found between genders. The SCD polymorphism had a greater impact on MUFA than using hams from barrows instead of gilts. It is concluded that the SCD polymorphism is a good tool to increase MUFA and MUFA/PUFA ratio in Duroc crossbred dry-cured hams. (Author)

  16. Polymorphisms in the genes ERCC2, XRCC3 and CD3EAP influence treatment outcome in multiple myeloma patients undergoing autologous bone marrow transplantation

    DEFF Research Database (Denmark)

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

    2007-01-01

    ) of polymorphism in the DNA repair genes ERCC1, ERCC2 and XRCC3, and in the apoptotic genes PPP1R13L and CD3EAP in 348 patients with multiple myeloma undergoing autologous bone marrow transplantation. Carriers of the variant C-allele of ERCC2 K751Q, the variant T-allele of XRCC3 T241M and the variant A...... the outcome for patients treated with autologous stem cell transplantation. Udgivelsesdato: 2007-Mar-1...

  17. Impulsive traits and 5-HT2A receptor promoter polymorphism in alcohol dependents: Possible association but no influence of personality disorders

    OpenAIRE

    Preuss, Ulrich W.; Koller, G.; Bondy, Brigitta; Bahlmann, Miriam; Soyka, Michael

    2001-01-01

    Objective: Impulsive behavior in alcoholics puts them at serious risk of severer course of disease and has been related to the serotonergic neurotransmission dysfunction. The aim of this study is to investigate the association between impulsive aggression in alcohol dependents with regard to the G-1438A polymorphism in the promoter region of the 5-HT2A receptor gene. Furthermore, we investigated the statistical interaction between 5-HT2A alleles, antisocial personality disorder (APD) and impu...

  18. Influence of asymmetrical mating patterns and male reproductive success on the maintenance of sexual polymorphism in Acer pictum subsp. mono (Aceraceae).

    Science.gov (United States)

    Shang, Hui; Luo, Yi-Bo; Bai, Wei-Ning

    2012-08-01

    Populations of Acer species often contain more than three sex phenotypes with complex sexual polymorphism including duodichogamy, protandry and protogyny. We identified the mechanisms that maintain sexual polymorphism in Acer pictum subsp. mono, a temperate tree from northern China, by investigating maternal mating patterns and male reproductive success. We used paternity analyses to estimate rates of outcrossing and disassortative mating, as well as male outcrossed siring success, in a population of A. pictum subsp. mono with uneven sex phenotype ratios (duodichogamous 69.1%, protandrous 19.6%, protogynous 11.3%). We used a pollen-transfer model to investigate whether the unequal ratios of sex phenotypes could be explained by the observed patterns of mating. Most progeny resulted from outcrossing, particularly disassortative among the sex phenotypes. Although the duodichogamous phenotype showed a significant amount of intraphenotypic mating, the frequency did not exceed that of disassortative mating. We detected no significant differences in male outcrossed siring success among the sex phenotypes. The pollen-transfer model demonstrated that sex phenotype ratios could be maintained by the observed mating pattern in the population. Our results indicate that disassortative mating among the sex phenotypes can maintain sexual polymorphism in A. pictum subsp. mono and that ratios biased towards duodichogamy can result from frequent intraphenotypic mating in this phenotype. © 2012 Blackwell Publishing Ltd.

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

    Science.gov (United States)

    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.

  20. Dietary carotenoid-rich oil supplementation improves exercise-induced anisocytosis in runners: influences of haptoglobin, MnSOD (Val9Ala), CAT (21A/T) and GPX1 (Pro198Leu) gene polymorphisms in dilutional pseudoanemia (sports anemia).

    Science.gov (United States)

    Miranda-Vilela, Ana L; Akimoto, Arthur K; Alves, Penha C Z; Pereira, Luiz C S; Klautau-Guimarães, Maria N; Grisolia, Cesar K

    2010-04-01

    Physical training induces beneficial adaptation, whereas exhaustive exercises increase reactive oxygen-species generation, thereby causing oxidative damage in plasma and erythrocytes, fractions susceptible to lipid peroxidation. Pequi (Caryocar brasiliense Camb.) is a Brazilian Cerrado fruit containing a carotenoid-rich oil. The aim was to investigate the effects of pequi-oil on exercise-induced oxidative damage in plasma and erythrocytes, after running in the same environment and undergoing weekly training under the same conditions as to type, intensity and length. Evaluations were accomplished after outdoor running on flat land before and after ingestion of 400 mg pequi-oil capsules for 14 days. Blood samples were taken after running and submitted to TBARS assay and erythrogram analysis. Haptoglobin, MnSOD (Val9Ala), CAT (21A/T) and GPX1 (Pro198Leu) gene polymorphisms were priorly investigated, so as to estimate genetic influence The reduction in erythrocytes, hemoglobin and hematocrit after pequi-oil treatment was notably associated with higher plasma expansion. Except for MCHC (mean corpuscular hemoglobin concentration) and RDW (red cell distribution width), the results were influenced by the polymorphisms studied. The best response to pequi-oil was presented by MnSOD Val/Val, CAT AA or AT genotypes and the GPX1 Pro allele. The significantly lower RDW and higher MHCH values were related to pequi-oil protective effects. Pequi oil, besides possessing other nutritional properties, showed protective blood effects.

  1. Dietary carotenoid-rich oil supplementation improves exercise-induced anisocytosis in runners: influences of haptoglobin, MnSOD (Val9Ala, CAT (21A/T and GPX1 (Pro198Leu gene polymorphisms in dilutional pseudoanemia ("sports anemia"

    Directory of Open Access Journals (Sweden)

    Ana L. Miranda-Vilela

    2010-01-01

    Full Text Available Physical training induces beneficial adaptation, whereas exhaustive exercises increase reactive oxygen-species generation, thereby causing oxidative damage in plasma and erythrocytes, fractions susceptible to lipid peroxidation. Pequi (Caryocar brasiliense Camb. is a Brazilian Cerrado fruit containing a carotenoid-rich oil. The aim was to investigate the effects of pequi-oil on exercise-induced oxidative damage in plasma and erythrocytes, after running in the same environment and undergoing weekly training under the same conditions as to type, intensity and length. Evaluations were accomplished after outdoor running on flat land before and after ingestion of 400 mg pequi-oil capsules for 14 days. Blood samples were taken after running and submitted to TBARS assay and erythrogram analysis. Haptoglobin, MnSOD (Val9Ala, CAT (21A/T and GPX1 (Pro198Leu gene polymorphisms were priorly investigated, so as to estimate genetic influence The reduction in erythrocytes, hemoglobin and hematocrit after pequi-oil treatment was notably associated with higher plasma expansion. Except for MCHC (mean corpuscular hemoglobin concentration and RDW (red cell distribution width, the results were influenced by the polymorphisms studied. The best response to pequi-oil was presented by MnSOD Val/Val, CAT AA or AT genotypes and the GPX1 Pro allele. The significantly lower RDW and higher MHCH values were related to pequi-oil protective effects. Pequi oil, besides possessing other nutritional properties, showed protective blood effects.

  2. [The influence of hormonal replacement therapy on bone density in postmenopausal women depending on polymorphism of vitamin D receptor (VDR) and estrogen receptor (ER) genes].

    Science.gov (United States)

    Brodowska, Agnieszka

    2003-01-01

    Osteoporosis is still an important health problem in modern societies. The densitometric criterion for the diagnosis of this condition established by WHO in 1994 is bone mass density (BMD) lower than 2.5 standard deviation (SD) from the mean value for young healthy individuals of the same sex. Between 60 and 90% of bone density (quantity of bone tissue in the human skeleton) at the time when growth is terminated is genetically determined. For this reason, genes predisposing to osteoporosis and mechanisms of their activity remain the object of investigations. Among them are genes coding for vitamin D receptor (VDR), estrogen receptor (ER), type I collagen, TGF-beta and IL-6. Diminishing bone density past the age of thirty is a physiologic process. Bone loss averages 0.3-0.6% per year. Acceleration of this process to 1.2-6% per year in postmenopausal women has been attributed to constantly decreasing estrogen concentration. Hence, the gold standard in osteoporosis prevention and treatment includes estrogen-progestagen therapy enriched with vitamin D analogues, calcium-rich diet and regular physical exercises. Treatment of osteoporosis can be long and expensive. The condition may lead to disability. Osteoporotic fractures and their complications may be fatal. For these reasons, the chief priority in osteoporosis is prevention. Unfortunately, current diagnostic methods (for detection of osteoporosis and monitoring of treatment) remain unsatisfactory. Molecular techniques offer a promising approach to diagnosis and monitoring of therapy. Additionally, the risk of osteoporosis in 1st degree relatives can be assessed and early prevention can be started. The present study addressed the following questions: 1. Are there differences in spine BMD in untreated women with postmenopausal osteoporosis depending on polymorphism of VDR and ER genes? 2. Does efficacy of treatment (increase in spine BMD) in women with postmenopausal osteoporosis depend on polymorphism of VDR and ER

  3. 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...

  4. Warfarin dose requirement in Turkish patients: the influences of patient characteristics and polymorphisms in CYP2C9, VKORC1 and factor VII.

    Science.gov (United States)

    Yildirim, E; Erol, K; Birdane, A

    2014-01-01

    To determine the contribution of cytochrome P4502C9 (CYP2C9), vitamin K epoxide reductase (VKORC1) and factor VII genotypes, age, body mass index (BMI), international normalized ratio (INR) and other individual patient characteristics on warfarin dose requirements in an adult Turkish population. Blood samples were collected from 101 Turkish patients. Genetic analyses for CYP2C9*2 and *3, VKORC1 -1639 G>A and factor VII -401 G>T polymorphisms were performed. Age, INR, BMI values and other individual patient characteristics were also recorded. The mean daily warfarin dosage was significantly higher in patients with the CYP2C9*1/*1 genotype than in the CYP2C9*2/*2 and CYP2C9*1/*3 groups (p ≤ 0.05). With respect to the VKORC1 -1639 G>A polymorphism, the mean warfarin daily dose requirement was higher in the wild type group compared to the heterozygous group (p≤0.001). The mean daily dose requirement for patients with the GG form of factor VII was significantly higher than that of patients with the TT genotype (p ≤ 0.05). Age, gender, BMI, INR had no statistically significant correlation with warfarin dose (p ≥ 0.05). Polymorphisms in CYP2C9, VKORC1 and factor VII did partially affect daily warfarin dose requirements, while age, gender, BMI and INR do not. However, further case-control studies with a larger study size and different genetic loci are needed to confirm our study.

  5. Influence of angiotensin converting enzyme (ACE) gene rs4362 polymorphism on the progression of kidney failure in patients with autosomal dominant polycystic kidney disease (ADPKD).

    Science.gov (United States)

    Ramanathan, Gnanasambandan; Ghosh, Santu; Elumalai, Ramprasad; Periyasamy, Soundararajan; Lakkakula, Bhaskar V K S

    2016-06-01

    Autosomal dominant polycystic kidney disease (ADPKD) is an inherited systemic disorder, characterized by the fluid filled cysts in the kidneys leading to end stage renal failure in later years of life. Hypertension is one of the major factors independently contributing to the chronic kidney disease (CKD) progression. The renin-angiotensin aldosterone system (RAAS) genes have been extensively studied as hypertension candidate genes. The aim of the present study was to investigate the role of angiotensin converting enzyme tagging - single nucleotide polymorphisms (ACE tag-SNPs) in progression of CKD in patients with ADPKD. m0 ethods: In the present study six ACE tagSNPs (angiotensin converting enzyme tag single nucleotide polymorphisms) and insertion/deletion (I/D) in 102 ADPKD patients and 106 control subjects were investigated. The tagSNPs were genotyped using FRET-based KASPar method and ACE ID by polymerase chain reaction (PCR) and electrophoresis. Genotypes and haplotypes were compared between ADPKD patients and controls. Univariate and multivariate logistic regression analyses were performed to assess the effect of genotypes and hypertension on CKD advancement. Mantel-Haenszel (M-H) stratified analysis was performed to study the relationship between different CKD stages and hypertension and their interaction. All loci were polymorphic and except rs4293 SNP the remaining loci followed Hardy-Weinberg equilibrium. Distribution of ACE genotypes and haplotypes in controls and ADPKD patients was not significant. A significant linkage disequilibrium (LD) was observed between SNPs forming two LD blocks. The univariate analysis revealed that the age, hypertension, family history of diabetes and ACE rs4362 contributed to the advancement of CKD. The results suggest that the ACE genotypes are effect modifiers of the relationship between hypertension and CKD advancement among the ADPKD patients.

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

    Science.gov (United States)

    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.

  7. Influence of eNOS gene 4a/bVNTR polymorphism on development of endothelial dysfunction and respiratory system disorders in children - residents of radioactively contaminated areas

    International Nuclear Information System (INIS)

    Stepanova, Je.Yi.; Kolpakov, Yi.Je.; Zigalo, V.M.; And Others

    2015-01-01

    Total of 184 children were examined to determine the possible associative links between eNOS gene intron 4m polymorphism and indices characterizing the functional state of the endothelium and the bronchopulmonary system. Of them the main group of children consisted of 135 childrenresidents of radioactively contaminated areas, the control group - of 49 healthy children who lived in ''clean'' regions by the radioactive con tamination and were not belonging to victims of the Chernobyl accident contingents. The molecular genetic study determining the eNOS gene intron 4 polymorphism was performed. Children of the main group did not differ from that of control and literature data by the frequency of geno types 4a/b and eNOS gene allele polymorphism. An increase in the duration of circulation restoration up to the ini tial level after occlusion test was noted in children of the main group with genotype 4a/4b comparing to children with genotype 4b/4b ; a decrease in the nitrite content was observed in blood serum. The integral indices of elastic ity and tensility of the lung tissue, respiratory permeability were decreased; the signs of bronchospasm were record ed 1.5 times more often. These adverse effects were associated with the presence of genotype allele 4a , the signs of endothelial dysfunction and the level of the incorporated 137 Cs. More pronounced changes in vascular endothelial reaction to occlusion and the significant decrease of serum nitrite level in allele 4a carriers, especially in children who live in adverse ecological conditions, give the right to include them into the risk group for the development of endothelial dysfunction, and to conside pulmonary dysfunction as one of its manifestations

  8. A single nucleotide polymorphism within the novel sex-linked testis-specific retrotransposed PGAM4 gene influences human male fertility.

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    Hidenobu Okuda

    Full Text Available The development of novel fertilization treatments, including in vitro fertilization and intracytoplasmic injection, has made pregnancy possible regardless of the level of activity of the spermatozoa; however, the etiology of male-factor infertility is poorly understood. Multiple studies, primarily through the use of transgenic animals, have contributed to a list of candidate genes that may affect male infertility in humans. We examined single nucleotide polymorphisms (SNPs as a cause of male infertility in an analysis of spermatogenesis-specific genes.We carried out the prevalence of SNPs in the coding region of phosphoglycerate mutase 4 (PGAM4 on the X chromosome by the direct sequencing of PCR-amplified DNA from male patients. Using RT-PCR and western blot analyses, we identified that PGAM4 is a functional retrogene that is expressed predominantly in the testes and is associated with male infertility. PGAM4 is expressed in post-meiotic stages, including spermatids and spermatozoa in the testes, and the principal piece of the flagellum and acrosome in ejaculated spermatozoa. A case-control study revealed that 4.5% of infertile patients carry the G75C polymorphism, which causes an amino acid substitution in the encoded protein. Furthermore, an assay for enzymatic activity demonstrated that this polymorphism decreases the enzyme's activity both in vitro and in vivo.These results suggest that PGAM4, an X-linked retrogene, is a fundamental gene in human male reproduction and may escape meiotic sex chromosome inactivation. These findings provide fresh insight into elucidating the mechanisms of male infertility.

  9. High-dose folic acid supplementation alters the human sperm methylome and is influenced by the MTHFR C677T polymorphism.

    Science.gov (United States)

    Aarabi, Mahmoud; San Gabriel, Maria C; Chan, Donovan; Behan, Nathalie A; Caron, Maxime; Pastinen, Tomi; Bourque, Guillaume; MacFarlane, Amanda J; Zini, Armand; Trasler, Jacquetta

    2015-11-15

    Dietary folate is a major source of methyl groups required for DNA methylation, an epigenetic modification that is actively maintained and remodeled during spermatogenesis. While high-dose folic acid supplementation (up to 10 times the daily recommended dose) has been shown to improve sperm parameters in infertile men, the effects of supplementation on the sperm epigenome are unknown. To assess the impact of 6 months of high-dose folic acid supplementation on the sperm epigenome, we studied 30 men with idiopathic infertility. Blood folate concentrations increased significantly after supplementation with no significant improvements in sperm parameters. Methylation levels of the differentially methylated regions of several imprinted loci (H19, DLK1/GTL2, MEST, SNRPN, PLAGL1, KCNQ1OT1) were normal both before and after supplementation. Reduced representation bisulfite sequencing (RRBS) revealed a significant global loss of methylation across different regions of the sperm genome. The most marked loss of DNA methylation was found in sperm from patients homozygous for the methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism, a common polymorphism in a key enzyme required for folate metabolism. RRBS analysis also showed that most of the differentially methylated tiles were located in DNA repeats, low CpG-density and intergenic regions. Ingenuity Pathway Analysis revealed that methylation of promoter regions was altered in several genes involved in cancer and neurobehavioral disorders including CBFA2T3, PTPN6, COL18A1, ALDH2, UBE4B, ERBB2, GABRB3, CNTNAP4 and NIPA1. Our data reveal alterations of the human sperm epigenome associated with high-dose folic acid supplementation, effects that were exacerbated by a common polymorphism in MTHFR. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  10. Arg16Gly and Gln27Glu β2 adrenergic polymorphisms influence cardiac autonomic modulation and baroreflex sensitivity in healthy young Brazilians

    Science.gov (United States)

    Atala, Magda M; Goulart, Alessandra; Guerra, Grazia M; Mostarda, Cristiano; Rodrigues, Bruno; Mello, Priscila R; Casarine, Dulce E; Irigoyen, Maria-Claudia; Pereira, Alexandre C; Consolim-Colombo, Fernanda M

    2015-01-01

    The association between functional β2 adrenergic receptor (β2-AR) polymorphisms and cardiac autonomic modulation is still unclear. Thus, two common polymorphisms in the β2-AR gene (Gln27Glu β2 and Arg16Gly β2) were studied to determine whether they might affect tonic and reflex cardiac sympathetic activity in healthy young subjects. A total of 213 healthy young white subjects of both genders (53% female), aged 18-30 years (23.5±3.4 y), had their continuous blood pressure curves noninvasively recorded by Finometer at baseline, and other hemodynamic parameters, as cardiac autonomic modulation, baroreflex sensitivity, and allele, genotype, and diplotype frequencies calculated. Associations were made between Arg16Gly β2 and Gln27Glu β2 polymorphisms and between β2-AR diplotypes and all variables. The heart rate was significantly lower (P<0.001) in the presence of homozygous Arg/Arg alleles (60.9±1.5 bpm) than in that of Arg/Gly heterozygotes (65.9±1.0 bpm) or Gly/Gly homozygotes (66.3±1.2 bpm). Homozygous carriers of Arg16 allele had an alpha index (19.2±1.3) significantly higher (P<0.001) than that of the subjects with the Gly allele Gly/Gly (14.5±0.7) or Arg/Gly (14.6±0.7). Furthermore, the recessive Glu27Glu and the heterozygous Gln27Glu genotypes had a higher percentage of low-frequency components (LF%) than the homozygous Gln27Gln (15.1% vs. 16.0% vs. 8.2%, P=0.03, respectively). In healthy young subjects, the presence of β2-AR Arg16 allele in a recessive model was associated with higher baroreflex sensitivity, and increased parasympathetic modulation in studied individuals. PMID:25755837

  11. The plasminogen activator inhibitor-1 (PAI-1) gene -844 A/G and -675 4G/5G promoter polymorphism significantly influences plasma PAI-1 levels in women with polycystic ovary syndrome.

    Science.gov (United States)

    Lin, Sun; Huiya, Zhang; Bo, Liu; Wei, Wei; Yongmei, Guan

    2009-12-01

    Mutations in the plasminogen activator inhibitor-1 (PAI-1) gene, along with increased PAI-1 levels, have been implicated in the pathogenesis of polycystic ovarian syndrome (PCOS). We investigated a possible influence of the promoter polymorphism (-844 A/G and -675 4G/5G) in the PAI-1 gene on plasma PAI-1 levels in 126 PCOS patients and 97 healthy controls. Levels of total testosterone, luteinizing hormone (LH), follicle stimulating hormone (FSH), fasting plasma glucose (FPG), fasting insulin, and PAI-1 were measured, and body mass index (BMI), waist-to-hip ratio (WHR), LH/FSH ratio, and homeostasis model assessment for insulin resistance (HOMA-IR) were calculated. PAI-1 -675 4G/5G and -844 A/G gene polymorphisms were also performed. Total testosterone, fasting insulin, and PAI-1 levels; BMI, LH/FSH, and HOMA-IR were significantly higher in PCOS patients than controls (P 5G or 5G/5G genotype. The plasma PAI-1 levels of the combination of the PAI-1 -844 A/A and -675 4G/4G or 4G/5G genotypes, or the coadunation of 4G/4G and -844 non-G/G (A/A + A/G) genotypes were significantly high in PCOS women compared with controls. A trend to a positive interaction between PAI-1 -675 4G/5G and -844 A/G gene polymorphism may elevate plasma PAI-1 levels and hypofibrinolysis, which is probably an important hereditary risk factor in PCOS.

  12. Quantitative assessment of the influence of TP63 gene polymorphisms and lung cancer risk: evidence based on 93,751 subjects.

    Directory of Open Access Journals (Sweden)

    Liang Zhang

    Full Text Available BACKGROUND: Several genome-wide association studies on lung cancer (LC have reported similar findings of a new susceptibility locus, 3q28. After that, a number of studies reported that the rs10937405, and rs4488809 polymorphism in chromosome 3q28 has been implicated in LC risk. However, the studies have yielded contradictory results. METHODS: PubMed, ISI web of science, EMBASE and the Chinese National Knowledge Infrastructure databases were systematically searched to identify relevant studies. Data were abstracted independently by two reviewers. A meta-analysis was performed to examine the association between rs10937405, rs4488809 polymorphism at 3q28 and susceptibility to LC. Odds ratios (ORs and 95% confidence intervals (95% CIs were calculated. Heterogeneity and publication bias were also tested. RESULTS: A total of 9 studies including 35,961 LC cases and 57,790 controls were involved in this meta-analysis. An overall random-effects per-allele OR of1.19 (95% CI: 1.14-1.25; P<10(-5 and 1.19 (95% CI: 1.13-1.25; P<10(-5 was found for the rs10937405 and rs4488809 polymorphism respectively. Similar results were also observed using dominant or recessive genetic model. After stratified by ethnicity, significant associations were found among East Asians (per-allele OR = 1.22, 95% CI: 1.17-1.27; P<10(-5; whereas no significant associations were found among Caucasians for rs10937405. In the sub-group analysis by sample size, significantly increased risks were found for these polymorphisms in all genetic models. When analyzed according to histological type, the effects of rs10937405, and rs4488809 at 3q28 on the risk of lung cancer were significant mostly for lung adenocarcinoma. CONCLUSIONS: Our findings demonstrated that rs10937405-G allele and rs4488809-G allele might be risk-conferring factors for the development of lung cancer, especially for East Asian populations.

  13. Impulsive traits and 5-HT2A receptor promoter polymorphism in alcohol dependents: possible association but no influence of personality disorders.

    Science.gov (United States)

    Preuss, U W; Koller, G; Bondy, B; Bahlmann, M; Soyka, M

    2001-01-01

    Impulsive behavior in alcoholics puts them at serious risk of severer course of disease and has been related to the serotonergic neurotransmission dysfunction. The aim of this study is to investigate the association between impulsive aggression in alcohol dependents with regard to the G-1438A polymorphism in the promoter region of the 5-HT2A receptor gene. Furthermore, we investigated the statistical interaction between 5-HT2A alleles, antisocial personality disorder (APD) and impulsive aggression in alcohol dependents. Alcohol dependents were investigated because these personality disorders and impulsive behavior are very frequent in alcohol dependence anf of clinical relevance. One hundred and thirty-five patients of German descent meeting DSM-IV criteria of alcohol dependence were recruited. Blood samples were taken from alcohol dependents to determine 5-HT2A promoter polymorphisms using PCR (polymerase chain reaction) of lymphocyte DNA. Impulsive aggression was assessed using a German version of the Barratt Impulsiveness Scale which was translated and backtranslated. Alcohol dependents were subdivided into low- or high-impulsivity groups using a median split of the Barratt score. APD and borderline personality disorder (BPD) were assessed using the SCID-II interview. The low-impulsivity group was slightly older and showed a later age at alcoholism onset than the highly impulsive group. Alcohol dependents with high impulsive traits showed a significant association with 5-HT2A 1438 A alleles. After excluding alcohol dependents with APD or BPD from the analysis, this association remained significant. Furthermore, no association between APD, BPD and 5-HT2A alleles was noted. Inpatient alcohol dependents showed a significant association between 5-HT2A A alleles and impulsive traits, independent of the presence of APD or BPD. No association was noted between personality disorders and the polymorphism. This is the first report about an association of 5-HT2A promoter

  14. Aragonite–calcite–vaterite: A temperature influenced sequential polymorphic transformation of CaCO{sub 3} in the presence of DTPA

    Energy Technology Data Exchange (ETDEWEB)

    Gopi, Shanmukhaprasad [Department of Chemistry, Annamalai University, Annamalainagar 608002, Tamilnadu (India); Subramanian, V.K., E-mail: drvksau@gmail.com [Department of Chemistry, Annamalai University, Annamalainagar 608002, Tamilnadu (India); Palanisamy, K. [Department of Chemistry, Annamalai University, Annamalainagar 608002, Tamilnadu (India)

    2013-05-15

    Highlights: ► Crystallization of CaCO{sub 3} between 60 and 230 °C in the presence of DTPA. ► Formation of exclusive and individual polymorphs at different temperatures. ► Violation of second law of thermodynamics/Ostwald rule of stages has been observed. - Abstract: Calcium carbonate was precipitated from calcium chloride using sodium carbonate in the presence of diethylenetriaminepentaacetic acid (DTPA) between 60 and 230 °C. The samples were characterized by FTIR, Raman, XRD and SEM techniques. CaCO{sub 3} with different crystal morphologies such as spherolite/datura pod, dumbbell, peanut, were obtained depending on the experimental conditions. The results showed that pure aragonite, calcite and vaterite were formed at low, moderate and high temperatures respectively. A binary mixture of calcite and vaterite was resulted between 150 and 200 °C. The data suggested an unusual conversion of stable calcite to meta stable vaterite at higher temperature in presence of DTPA. The study revealed a novel methodology for the exclusive/individual preparation of different crystalline polymorphs of CaCO{sub 3}. Formation of pure vaterite above 200 °C divulged the possibility of DTPA as a potential scale inhibitor and boiler sludge conditioner at elevated temperatures.

  15. Influence of G308A polymorphism of tumor necrosis factor-alpha gene on inflammatory markers in postsurgical head and neck cancer patients with early enteral nutrition.

    Science.gov (United States)

    de Luis, Daniel Antonio; Sagrado, Manue Gonzalez; Vallejo, Luis Angel; Carcedo, Luis María Gil; Izaola, Olatz; Cuellar, Luis; Terroba, María Concepción; Aller, Rocío

    2007-01-01

    Although immune dysfunction in patients with cancer could be multifactorial, the immune system may be modulated by nutritional substrates and genetic background. Our study evaluated the effect of G308A polymorphism of the tumor necrosis factor-alpha (TNF-alpha) gene on inflammatory markers in patients after surgery for head and neck cancer who received early enteral nutrition. A population of 60 patients with oral and laryngeal cancer was enrolled. At surgery patients were treated with a hyperproteic enteral diet. Perioperatively and on postoperative day 6 the following parameters were evaluated: serum values of prealbumin, transferrin, total number of lymphocytes, interleukin-6, TNF-alpha, and C-reactive protein. In addition, genotyping of G308A gene polymorphism was assessed. Patients' mean age was 61.1 +/- 14.6 y (four women, 56 men) with a body mass index of 25.4 +/- 5.2 kg/m(2) and a previous weight loss of 0.35 +/- 0.2 kg. Forty patients (37 men, 3 women; 66.6%) had the genotype G308/G308 (wild group) and 20 patients (19 men, 1 woman; 23.4%) had the genotype G308/A308 (mutant group). A significant increase in prealbumin and transferrin levels was detected in both groups. C-reactive protein decreased in both groups (wild group: 105.1 +/- 60 versus 53.8 +/- 62.3 mg/dL, P < 0.05; mutant group: 99.5 +/- 46 versus 43.9 +/- 51.9 mg/dL, P < 0.05). Interleukin-6 decreased in both groups (wild group: 20.1 +/- 22 versus 6.2 +/- 4.1 pg/mL, P < 0.05; mutant group: 22.3 +/- 38 versus 9.2 +/- 7.4 pg/mL, P = NS). Lymphocytes increased in both groups (wild group: 1102 +/- 468 versus 1600 +/- 537 10(3)/mL, P = NS; mutant group: 1441 +/- 739 10(3)/mL versus 1669 +/- 614 10(6)/mL, P = NS). TNF-alpha showed no changes. The G308A polymorphism of the TNF-alpha gene did not affect levels of inflammatory markers in patients after surgery for head and neck cancer who were treated with early enteral nutrition.

  16. Influence of the glutation S-transferases T1 and M1 gene polymorphisms on androgenic status and semen quality after surgical treatment of varicocele

    Directory of Open Access Journals (Sweden)

    P. V. Glybochko

    2013-01-01

    Full Text Available Aim: to examine androgenic status in men after surgical treatment of varicocele; to investigate genotype GSTT1 and GSTM1 in patients with pathozoospermia. Thirty men after surgical treatment of varicocele were recruited to this study. All subjects were evaluated by history, physical examination, semen analysis, serum FSH, LH, E2, PL, inhibin B and total testosterone determination. GSTT1, CSTM1 gene polymorphisms were determined by polymerase chain reaction. Total testosterone and inhibin B levels were significantly lower in patients with pathozoospermia. Patients with the GSTM1(- genotype had lower sperm concentrations than those with the GSTM1(+ genotype.Our results suggest that the GSTM1(- genotype is risk factor for androgen deficiency and pathozoospermia.

  17. Influence of genetic polymorphisms of IL23R, STAT3, IL12B, and STAT4 on the risk of aplastic anemia and the effect of immunosuppressive therapy.

    Science.gov (United States)

    Zhao, Li; Zhu, Huanling; Han, Bing; Wang, Lixin; Sun, Yuming; Lu, Xiaojun; Huang, Chunyan; Tan, Bin; Chen, Chunxia; Qin, Li

    2018-04-01

    Studies have suggested that IL-23/STAT3 and IL-12/STAT4 signaling pathways associate with aplastic anemia (AA) occurrence. Polymorphisms in pathway-related genes may contribute to AA risk. In the current study, we investigated the association between polymorphisms in genes of IL23R, STAT3, IL12B, and STAT4 and occurrence, severity, and immunosuppressive outcome of AA in the Han population in southwest China. In the current 164 AA cases and 211 controls study, we found T allele and TT genotype of rs7574865 were more frequent in the cases than that in the controls. In the additive model, individual carrying rs7574865 T allele demonstrated a 37% (OR (95% CI) = 1.37 (1.02-1.85), Pper = 0.036) increased AA risk. In the recessive model, carrier with rs7574865 TT genotype showed a 2.08-fold increased AA risk (OR (95% CI) = 2.08 (1.14-3.70), Pper = 0.017). Additionally, we showed that G allele and GG genotype of rs11209032 were more frequent in the 88 non-severe AA cases than that in the 76 severe AA ones. Our study also found G allele and GG genotype of rs11209032, and GG-genotype of rs744166 associated with the immunosuppressive therapy outcome in AA patients. Current study results support that functional STAT4 (rs7574865), IL23R (rs11209032), and STAT3 (rs744166) variants may associate with occurrence, severity, and immunosuppressive outcome of AA in the Han population in southwest China.

  18. The maternal homocysteine pathway is influenced by riboflavin intake and MTHFR polymorphisms without affecting the risk of orofacial clefts in the offspring.

    Science.gov (United States)

    Vujkovic, M; Steegers, E A; van Meurs, J; Yazdanpanah, N; van Rooij, I A; Uitterlinden, A G; Steegers-Theunissen, R P

    2010-03-01

    Riboflavin is a cofactor for the 5,10-methylenetetrahydrofolate reductase (MTHFR) enzyme involved in the homocysteine pathway. The aim of this study was to investigate the effects of maternal riboflavin intake and two MTHFR polymorphisms (677C>T; Ala222Val and 1298A>C; Glu429Ala substitutions) on the biomarkers of the homocysteine pathway, and investigate the risk of having offspring with an orofacial cleft (OFC). In a case-control study design, dietary riboflavin intake and the MTHFR 677C>T and 1298A>C polymorphisms were evaluated in 123 OFC and 108 control mothers by using food frequency questionnaires and blood samples. Homocysteine (tHcy), folate and vitamin B12 concentrations in blood were analyzed in 70 cases and 68 controls. Linear and logistic regression analyses were applied. At 14 months postpartum riboflavin intake and MTHFR 677C>T and 1298A>C genotypes were not significantly different between cases and controls. The 677TT genotype showed lower folate concentrations compared to C-allele carriers with a mean difference of 2.8 nmol/l in serum and 174 nmol/l in red blood cell (both P's=0.01). Every mg per day increase of dietary riboflavin intake was positively associated with increase in vitamin B12 concentration by 52.1% (Priboflavin-adjusted MTHFR 677TT and 1298CC genotypes showed a trend toward an increasing risk for OFC, adjusted odds ratio 1.7 (confidence interval (95% CI), 0.7-4.5) and 1.6 (95% CI, 0.7-4.2), respectively. Maternal riboflavin intake is significantly associated with biomarkers of the homocysteine pathway, with the strongest effects in MTHFR 677TT homozygotes. The maternal risk of having OFC offspring, however, is not associated with dietary riboflavin intake.

  19. Influence of PAI-1 gene promoter-675 (4G/5G) polymorphism on fibrinolytic activity after cardiac surgery employing cardiopulmonary bypass.

    Science.gov (United States)

    Ozolina, Agnese; Strike, Eva; Jaunalksne, Inta; Serova, Jelena; Romanova, Tatjana; Zake, Liene Nikitina; Sabelnikovs, Olegs; Vanags, Indulis

    2012-01-01

    The plasminogen activator inhibitor type-1 (PAI-1) gene promoter contains 675 (4G/5G) polymorphism. The aim of this study was evaluate the effect of the PAI-1 promoter-675 (4G/5G) polymorphism on the concentrations of PAI-1 and tissue plasminogen activator/PAI-1 (t-PA/PAI-1) complex and bleeding volume after on-pump cardiac surgery. A total of 90 patients were included in the study at Pauls Stradins Clinical University Hospital. Seven patients were excluded due to surgical bleeding. Eighty-three patients were classified according to the PAI-1 genotype: 21 patients had the 4G/4G genotype; 42, the 4G/5G genotype; and 20, the 5G/5G genotype. The following fibrinolysis parameters were recorded: the PAI-1 level preoperatively, D-dimer level at 0, 6, and 24 hours after surgery, and t-PA/PAI-1 complex level 24 hours postoperatively. A postoperative bleeding volume was registered in mL 24 hours after surgery. The patients with the 5G/5G genotype had significantly lower preoperative PAI-1 levels (17 [SD, 10.8] vs. 24 ng/mL [SD, 9.6], P=0.04), higher D-dimer levels at 6 hours (371 [SD, 226] vs. 232 ng/mL [SD, 185], P=0.03) and 24 hours (326 [SD, 207] vs. 209 ng/mL [SD, 160], P=0.04), and greater postoperative blood loss (568 [SD, 192] vs. 432 mL [168], P=0.02) compared with the 4G/4G carriers. There were no significant differences in the levels of the t-PA/PAI-1 complex comparing different genotype groups. The carriers of the 5G/5G genotype showed the lower preoperative PAI-1 levels, greater chest tube blood loss, and higher D-dimer levels indicating that the 5G/5G carriers may have enhanced fibrinolysis.

  20. Influence of CYP3A5 and ABCB1 gene polymorphisms on calcineurin inhibitor-related neurotoxicity after hematopoietic stem cell transplantation.

    Science.gov (United States)

    Yanagimachi, Masakatsu; Naruto, Takuya; Tanoshima, Reo; Kato, Hiromi; Yokosuka, Tomoko; Kajiwara, Ryosuke; Fujii, Hisaki; Tanaka, Fumiko; Goto, Hiroaki; Yagihashi, Tatsuhiko; Kosaki, Kenjiro; Yokota, Shumpei

    2010-01-01

    One severe side effect of calcineurin inhibitors (CNIs: such as cyclosporine [CsA] and tacrolimus [FK506]) is neurotoxicity. CNIs are substrates for CYP3A5 and P-glycoprotein (P-gp), encoded by ABCB1 gene. In the present study, we hypothesized that genetic variability in CYP3A5 and ABCB1 genes may be associated with CNI-related neurotoxicity. The effects of the polymorphisms, such as CYP3A5 A6986G, ABCB1 C1236T, G2677T/A, and C3435T, associated with CNI-related neurotoxicity were evaluated in 63 patients with hematopoietic stem cell transplantation.   Of the 63 cases, 15 cases developed CNI-related neurotoxicity. In the CsA patient group (n = 30), age (p = 0.008), hypertension (p = 0.017), renal dysfunction (p < 0.001), ABCB1 C1236T (p < 0.001), and G2677T/A (p = 0.014) were associated with neurotoxicities. The CC genotype at ABCB1 C1236T was associated with it, but not significantly so (p = 0.07), adjusted for age, hypertension, and renal dysfunction. In the FK506 patient group (n = 33), CYP3A5 A6986G (p < 0.001), and ABCB1 C1236T (p = 0.002) were associated with neurotoxicity. At least one A allele at CYP3A5 A6986G (expressor genotype) was strongly associated with it according to logistic regression analysis (p = 0.01; OR, 8.5; 95% CI, 1.4-51.4).   The polymorphisms in CYP3A5 and ABCB1 genes were associated with CNI-related neurotoxicity. This outcome is probably because of CYP3A5 or P-gp functions or metabolites of CNIs. © 2009 John Wiley & Sons A/S.

  1. Influence of polymorphisms within the methotrexate pathway genes on the toxicity and efficacy of methotrexate in patients with juvenile idiopathic arthritis.

    Science.gov (United States)

    Yanagimachi, Masakatsu; Naruto, Takuya; Hara, Takuma; Kikuchi, Masako; Hara, Ryoki; Miyamae, Takako; Imagawa, Tomoyuki; Mori, Masaaki; Kaneko, Tetsuji; Morita, Satoshi; Goto, Hiroaki; Yokota, Shumpei

    2011-02-01

    We investigated whether several polymorphisms within the methotrexate (MTX) pathway genes were related to the toxicity and efficacy of MTX in 92 Japanese patients with articular-type juvenile idiopathic arthritis (JIA). Eight gene polymorphisms within the MTX pathway genes, namely, RFC, BCRP, MTHFR (two), FPGS, γ-glutamyl hydrolase (GGH; two) and ATIC, were genotyped using TaqMan assays. Liver dysfunction was defined as an increase in alanine transaminase to five times the normal upper limit. Non-responders to MTX were defined as patients refractory to MTX and were therefore treated with biologics. The non-TT genotype at GGH T16C was associated with a high risk of liver dysfunction (P=0.028, odds ratio=6.90, 95% confidence interval 1.38-34.5), even after adjustment for the duration of MTX treatment. A longer interval from disease onset to treatment (8.5 and 21.3 months, P=0.029) and rheumatoid factor positivity (P=0.026, odds ratio=2.87, 95% confidence interval 1.11-7.39) were associated with lower efficacy of MTX. The non-TT genotype at GGH T16C was associated with a high risk of liver dysfunction, presumably because the C allele of GGH C16T may reduce the activity of GGH. The time interval before MTX treatment and rheumatoid factor positivity were associated with the efficacy of MTX treatment. The pharmacogenetics of the MTX pathway genes affects the toxicity and efficacy of MTX in Japanese JIA patients. © 2011 The Authors. British Journal of Clinical Pharmacology © 2011 The British Pharmacological Society.

  2. PDGFRα promoter polymorphisms and expression patterns influence risk of development of imatinib-induced thrombocytopenia in chronic myeloid leukemia: A study from India.

    Science.gov (United States)

    Guru, Sameer Ahmad; Mir, Rashid; Bhat, Musadiq; Najar, Imtiyaz; Zuberi, Mariyam; Sumi, Mamta; Masroor, Mirza; Gupta, Naresh; Saxena, Alpana

    2017-10-01

    Platelet-derived growth factor receptor has been implicated in many malignant and non-malignant diseases. Platelet-derived growth factor receptor-α is a tyrosine kinase and a side target for imatinib, a revolutionary drug for the treatment of chronic myeloid leukemia that has dramatically improved the survival of chronic myeloid leukemia patients. Given the importance of platelet-derived growth factor receptor in platelet development and its inhibition by imatinib, it was intriguing to analyze the role of platelet-derived growth factor receptor-α in relation to imatinib treatment in the development of imatinib-induced thrombocytopenia in chronic myeloid leukemia patients. We hypothesized that two known functional polymorphisms, +68GA insertion/deletion and -909C/A, in the promoter region of the platelet-derived growth factor receptor-α gene may affect the susceptibility of chronic myeloid leukemia patients receiving imatinib treatment to the development of thrombocytopenia. A case-control study was conducted among a cohort of chronic myeloid leukemia patients admitted to the Lok Nayak Hospital, New Delhi, India. A set of 100 patients of chronic myeloid leukemia in chronic phase and 100 age- and sex-matched healthy controls were studied. After initiation of imatinib treatment, the hematological response of chronic myeloid leukemia patients was monitored regularly for 2 years, in which the development of thrombocytopenia was the primary end point. Platelet-derived growth factor receptor-α promoter polymorphisms +68GA ins/del and -909C/A were studied by allele-specific polymerase chain reaction. Platelet-derived growth factor receptor-α messenger RNA expression was evaluated by quantitative real-time polymerase chain reaction. The messenger RNA expression results were expressed as 2 -Δct ± standard deviation. The distribution of +68GA ins/del promoter polymorphism genotypes differed significantly between the thrombocytopenic and non-thrombocytopenic chronic

  3. Polymorphous computing fabric

    Science.gov (United States)

    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.

  4. Urinary arsenic metabolism in a Western Chinese population exposed to high-dose inorganic arsenic in drinking water: Influence of ethnicity and genetic polymorphisms

    Energy Technology Data Exchange (ETDEWEB)

    Fu, Songbo [Center for Endemic Disease Control, Chinese Center for Disease Control and Prevention, Harbin Medical University, Key Lab of Etiology and Epidemiology, Education Bureau of Hei Long Jiang Province and Ministry of Health (23618104), Harbin 150081 (China); Wu, Jie [Laboratory of Medical Genetics, Harbin Medical University, Harbin 150081 (China); Li, Yuanyuan [Center for Endemic Disease Control, Chinese Center for Disease Control and Prevention, Harbin Medical University, Key Lab of Etiology and Epidemiology, Education Bureau of Hei Long Jiang Province and Ministry of Health (23618104), Harbin 150081 (China); Liu, Yan [Department of Health Statistics, Harbin Medical University, Harbin 150081 (China); Gao, Yanhui; Yao, Feifei [Center for Endemic Disease Control, Chinese Center for Disease Control and Prevention, Harbin Medical University, Key Lab of Etiology and Epidemiology, Education Bureau of Hei Long Jiang Province and Ministry of Health (23618104), Harbin 150081 (China); Qiu, Chuanying [Dongcheng District Center for Disease Control and Prevention, Beijing 100009 (China); Song, Li; Wu, Yu [Center for Endemic Disease Control, Chinese Center for Disease Control and Prevention, Harbin Medical University, Key Lab of Etiology and Epidemiology, Education Bureau of Hei Long Jiang Province and Ministry of Health (23618104), Harbin 150081 (China); Liao, Yongjian [Gansu Center for Disease Control and Prevention, 730020 (China); Sun, Dianjun, E-mail: hrbmusdj@163.com [Center for Endemic Disease Control, Chinese Center for Disease Control and Prevention, Harbin Medical University, Key Lab of Etiology and Epidemiology, Education Bureau of Hei Long Jiang Province and Ministry of Health (23618104), Harbin 150081 (China)

    2014-01-01

    To investigate the differences in urinary arsenic metabolism patterns of individuals exposed to a high concentration of inorganic arsenic (iAs) in drinking water, an epidemiological investigation was conducted with 155 individuals living in a village where the arsenic concentration in the drinking water was 969 μg/L. Blood and urine samples were collected from 66 individuals including 51 cases with skin lesions and 15 controls without skin lesions. The results showed that monomethylated arsenic (MMA), the percentage of MMA (%MMA) and the ratio of MMA to iAs (MMA/iAs) were significantly increased in patients with skin lesions as compared to controls, while dimethylated arsenic (DMA), the percentage of DMA (%DMA) and the ratio of DMA to MMA (DMA/MMA) were significantly reduced. The percent DMA of individuals with the Ala/Asp genotype of glutathione S-transferase omega 1 (GSTO1) was significantly lower than those with Ala/Ala. The percent MMA of individuals with the A2B/A2B genotype of arsenic (+ 3 oxidation state) methyltransferase (AS3MT) was significantly lower than those with AB/A2B. The iAs and total arsenic (tAs) content in the urine of a Tibetan population were significantly higher than that of Han and Hui ethnicities, whereas MMA/iAs was significantly lower than that of Han and Hui ethnicities. Our results showed that when exposed to the same arsenic environment, different individuals exhibited different urinary arsenic metabolism patterns. Gender and ethnicity affect these differences and above polymorphisms may be effectors too. - Highlights: • We first survey a village with high iAs content in the drinking water (969 μg/L). • 90 villagers suffered typical skin lesions with a morbidity rate of 58%. • Cases exhibited higher %MMA and MMA/iAs, and lower %DMA and DMA/MMA than controls. • Gender and ethnicity affect the differences of iAs methylation metabolism levels. • GSTO1 and AS3MT gene polymorphisms may be factors too.

  5. Urinary arsenic metabolism in a Western Chinese population exposed to high-dose inorganic arsenic in drinking water: Influence of ethnicity and genetic polymorphisms

    International Nuclear Information System (INIS)

    Fu, Songbo; Wu, Jie; Li, Yuanyuan; Liu, Yan; Gao, Yanhui; Yao, Feifei; Qiu, Chuanying; Song, Li; Wu, Yu; Liao, Yongjian; Sun, Dianjun

    2014-01-01

    To investigate the differences in urinary arsenic metabolism patterns of individuals exposed to a high concentration of inorganic arsenic (iAs) in drinking water, an epidemiological investigation was conducted with 155 individuals living in a village where the arsenic concentration in the drinking water was 969 μg/L. Blood and urine samples were collected from 66 individuals including 51 cases with skin lesions and 15 controls without skin lesions. The results showed that monomethylated arsenic (MMA), the percentage of MMA (%MMA) and the ratio of MMA to iAs (MMA/iAs) were significantly increased in patients with skin lesions as compared to controls, while dimethylated arsenic (DMA), the percentage of DMA (%DMA) and the ratio of DMA to MMA (DMA/MMA) were significantly reduced. The percent DMA of individuals with the Ala/Asp genotype of glutathione S-transferase omega 1 (GSTO1) was significantly lower than those with Ala/Ala. The percent MMA of individuals with the A2B/A2B genotype of arsenic (+ 3 oxidation state) methyltransferase (AS3MT) was significantly lower than those with AB/A2B. The iAs and total arsenic (tAs) content in the urine of a Tibetan population were significantly higher than that of Han and Hui ethnicities, whereas MMA/iAs was significantly lower than that of Han and Hui ethnicities. Our results showed that when exposed to the same arsenic environment, different individuals exhibited different urinary arsenic metabolism patterns. Gender and ethnicity affect these differences and above polymorphisms may be effectors too. - Highlights: • We first survey a village with high iAs content in the drinking water (969 μg/L). • 90 villagers suffered typical skin lesions with a morbidity rate of 58%. • Cases exhibited higher %MMA and MMA/iAs, and lower %DMA and DMA/MMA than controls. • Gender and ethnicity affect the differences of iAs methylation metabolism levels. • GSTO1 and AS3MT gene polymorphisms may be factors too

  6. Polymorphs and polymorphic cocrystals of temozolomide.

    Science.gov (United States)

    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.

  7. Electrostatic control of phospholipid polymorphism.

    Science.gov (United States)

    Tarahovsky, Y S; Arsenault, A L; MacDonald, R C; McIntosh, T J; Epand, R M

    2000-12-01

    A regular progression of polymorphic phase behavior was observed for mixtures of the anionic phospholipid, cardiolipin, and the cationic phospholipid derivative, 1, 2-dioleoyl-sn-glycero-3-ethylphosphocholine. As revealed by freeze-fracture electron microscopy and small-angle x-ray diffraction, whereas the two lipids separately assume only lamellar phases, their mixtures exhibit a symmetrical (depending on charge ratio and not polarity) sequence of nonlamellar phases. The inverted hexagonal phase, H(II,) formed from equimolar mixtures of the two lipids, i.e., at net charge neutrality (charge ratio (CR((+/-))) = 1:1). When one type of lipid was in significant excess (CR((+/-)) = 2:1 or CR((+/-)) = 1:2), a bicontinuous cubic structure was observed. These cubic phases were very similar to those sometimes present in cellular organelles that contain cardiolipin. Increasing the excess of cationic or anionic charge to CR((+/-)) = 4:1 or CR((+/-)) = 1:4 led to the appearance of membrane bilayers with numerous interlamellar contacts, i.e., sponge structures. It is evident that interactions between cationic and anionic moieties can influence the packing of polar heads and hence control polymorphic phase transitions. The facile isothermal, polymorphic interconversion of these lipids may have important biological and technical implications.

  8. An intronic polymorphism of IRF4 gene influences gene transcription in vitro and shows a risk association with childhood acute lymphoblastic leukemia in males.

    Science.gov (United States)

    Do, Thuy N; Ucisik-Akkaya, Esma; Davis, Charronne F; Morrison, Brittany A; Dorak, M Tevfik

    2010-02-01

    The interferon regulatory factor (IRF) family of DNA-binding proteins regulates expression of interferon-inducible genes with roles in the immune response and carcinogenesis. IRF4 is involved in the differentiation of B and T cells and is overexpressed in B-cell malignancies as a result of c-REL (NF-kappaB) hyperactivation. IRF4 polymorphisms are associated with susceptibility to chronic lymphoid leukemia (CLL) and non-Hodgkin lymphoma (NHL). We examined 13 IRF4 SNPs in 114 cases of childhood acute lymphoblastic leukemia (ALL) and 388 newborn controls from Wales (U.K.) using TaqMan assays. IRF4 intron 4 SNP rs12203592 showed a male-specific risk association (OR=4.4, 95% CI=1.5 to 12.6, P=0.007). Functional consequences of the C>T substitution at this SNP were assessed by cell-based reporter assays using three different cell lines. We found a repressive effect of the rs12203592 wildtype allele C on IRF4 promoter activity (Pcell line tested. Thus, homozygosity for the rs12203592 variant allele would result in increased IRF4 expression. This increase would be compounded by high levels of NF-kappaB activity in males due to the absence of estrogen. IRF4 differs from other IRFs in its anti-interferon activity which interferes with immune surveillance. We propose that a detailed study of IRF4 can provide information on the mechanism of the sex effect and the role of immune surveillance in childhood ALL development. Copyright 2009 Elsevier B.V. All rights reserved.

  9. The influence of the rs6295 gene polymorphism on serotonin-1A receptor distribution investigated with PET in patients with major depression applying machine learning.

    Science.gov (United States)

    Kautzky, A; James, G M; Philippe, C; Baldinger-Melich, P; Kraus, C; Kranz, G S; Vanicek, T; Gryglewski, G; Wadsak, W; Mitterhauser, M; Rujescu, D; Kasper, S; Lanzenberger, R

    2017-06-13

    Major depressive disorder (MDD) is the most common neuropsychiatric disease and despite extensive research, its genetic substrate is still not sufficiently understood. The common polymorphism rs6295 of the serotonin-1A receptor gene (HTR1A) is affecting the transcriptional regulation of the 5-HT 1A receptor and has been closely linked to MDD. Here, we used positron emission tomography (PET) exploiting advances in data mining and statistics by using machine learning in 62 healthy subjects and 19 patients with MDD, which were scanned with PET using the radioligand [carbonyl- 11 C]WAY-100635. All the subjects were genotyped for rs6295 and genotype was grouped in GG vs C allele carriers. Mixed model was applied in a ROI-based (region of interest) approach. ROI binding potential (BP ND ) was divided by dorsal raphe BP ND as a specific measure to highlight rs6295 effects (BP Div ). Mixed model produced an interaction effect of ROI and genotype in the patients' group but no effects in healthy controls. Differences of BP Div was demonstrated in seven ROIs; parahippocampus, hippocampus, fusiform gyrus, gyrus rectus, supplementary motor area, inferior frontal occipital gyrus and lingual gyrus. For classification of genotype, 'RandomForest' and Support Vector Machines were used, however, no model with sufficient predictive capability could be computed. Our results are in line with preclinical data, mouse model knockout studies as well as previous clinical analyses, demonstrating the two-pronged effect of the G allele on 5-HT 1A BP ND for, we believe, the first time. Future endeavors should address epigenetic effects and allosteric heteroreceptor complexes. Replication in larger samples of MDD patients is necessary to substantiate our findings.

  10. Allelic polymorphism of Makoei sheep leptin gene identified by ...

    African Journals Online (AJOL)

    use

    2011-12-05

    Dec 5, 2011 ... Lord et al., 1998) have shed light on the influence of leptin on both the .... A weak correlation between leptin serum levels and cow body condition ... Detection of polymorphisms in the ovine leptin (LEP) gene: .... Signals that.

  11. P-glycoprotein polymorphism and levothyroxine bioavailability in hypothyroid patients

    Directory of Open Access Journals (Sweden)

    Ezgi Öztaş

    2018-02-01

    Conclusion: Because of conflicted previous reports about the genetic contribution of MDR1 polymorphisms to drug disposition, further studies with large numbers of participants are required to clarify this influence.

  12. Folate intake, alcohol consumption, and the methylenetetrahydrofolate reductase (MTHFR C677T gene polymorphism: influence on prostate cancer risk and interactions

    Directory of Open Access Journals (Sweden)

    Lindsay C Kobayashi

    2012-08-01

    Full Text Available Purpose: Folate is essential to DNA methylation and synthesis and may have a complex dualistic role in prostate cancer. Alcohol use may increase risk and epigenetic factors may interact with lifestyle exposures. We aimed to characterize the independent and joint effects of folate intake, alcohol consumption, and the MTHFR C677T gene polymorphism on prostate cancer risk, while accounting for intakes of vitamins B2, B6, B12, methionine, total energy, and confounders.Methods: A case-control study was conducted at Kingston General Hospital of 80 incident primary prostate cancer cases and 334 urology clinic controls, all with normal age-specific PSA levels (to exclude latent prostate cancers. Participants completed a questionnaire on folate and alcohol intakes and potential confounders prior to knowledge of diagnosis, eliminating recall bias, and blood was drawn for MTHFR genotyping. Joint effects of exposures were assessed using unconditional logistic regression and significance of multiplicative and additive interactions using general linear models.Results: Folate, vitamins B2, B6, B12, methionine, and the CT and TT genotypes were not associated with prostate cancer risk. The highest tertile of lifetime alcohol consumption was associated with increased risk (OR=2.08; 95% CI: 1.12-3.86. Consumption of >5 alcoholic drinks/week was associated with increased prostate cancer risk among men with low folate intake (OR=2.38; 95% CI: 1.01-5.57 and higher risk among those with the CC MTHFR genotype (OR=4.43; 95% CI: 1.15-17.05. Increased risk was also apparent for weekly alcohol consumption when accounting for the multiplicative interaction between folate intake and MTHFR C677T genotype (OR=3.22; 95% CI: 1.36-7.59.Conclusion: Alcohol consumption is associated with increased prostate cancer risk, and this association is stronger among men with low folate intake, with the CC MTHFR genotype, and when accounting for the joint effect of folate intake and MTHFR C

  13. Folate intake, alcohol consumption, and the methylenetetrahydrofolate reductase (MTHFR) C677T gene polymorphism: influence on prostate cancer risk and interactions

    International Nuclear Information System (INIS)

    Kobayashi, Lindsay C.; Limburg, Heather; Miao, Qun; Woolcott, Christy; Bedard, Leanne L.; Massey, Thomas E.; Aronson, Kristan J.

    2012-01-01

    Purpose: Folate is essential to DNA methylation and synthesis and may have a complex dualistic role in prostate cancer. Alcohol use may increase risk and epigenetic factors may interact with lifestyle exposures. We aimed to characterize the independent and joint effects of folate intake, alcohol consumption, and the MTHFR C677T gene polymorphism on prostate cancer risk, while accounting for intakes of vitamins B 2 , B 6 , B 12 , methionine, total energy, and confounders. Methods: A case-control study was conducted at Kingston General Hospital of 80 incident primary prostate cancer cases and 334 urology clinic controls, all with normal age-specific PSA levels (to exclude latent prostate cancers). Participants completed a questionnaire on folate and alcohol intakes and potential confounders prior to knowledge of diagnosis, eliminating recall bias, and blood was drawn for MTHFR genotyping. Joint effects of exposures were assessed using unconditional logistic regression and significance of multiplicative and additive interactions using general linear models. Results: Folate, vitamins B 2 , B 6 , B 12 , methionine, and the CT and TT genotypes were not associated with prostate cancer risk. The highest tertile of lifetime alcohol consumption was associated with increased risk (OR = 2.08; 95% CI: 1.12–3.86). Consumption of >5 alcoholic drinks per week was associated with increased prostate cancer risk among men with low folate intake (OR = 2.38; 95% CI: 1.01–5.57), and higher risk among those with the CC MTHFR genotype (OR = 4.43; 95% CI: 1.15–17.05). Increased risk was also apparent for average weekly alcohol consumption when accounting for the multiplicative interaction between folate intake and MTHFR C677T genotype (OR = 3.22; 95% CI: 1.36–7.59). Conclusion: Alcohol consumption is associated with increased prostate cancer risk, and this association is stronger among men with low folate intake, with the CC MTHFR genotype, and when accounting for the joint effect

  14. Polymorphisms in apolipoprotein B and risk of ischemic stroke

    DEFF Research Database (Denmark)

    Benn, Marianne; Nordestgaard, Børge G; Jensen, Jan Skov

    2007-01-01

    Apolipoprotein B levels associate with risk of ischemic stroke. APOB polymorphisms may influence levels of apolipoprotein B and low-density lipoprotein (LDL), but whether they associate with risk of ischemic stroke is unknown.......Apolipoprotein B levels associate with risk of ischemic stroke. APOB polymorphisms may influence levels of apolipoprotein B and low-density lipoprotein (LDL), but whether they associate with risk of ischemic stroke is unknown....

  15. Chromosomal aberrations in humans induced by urban air pollution: influence of DNA repair and polymorphisms of glutathione S-transferase M1 and N-acetyltransferase 2

    DEFF Research Database (Denmark)

    Knudsen, Lisbeth E.; Norppa, H; Gamborg, M O

    1999-01-01

    We have studied the influence of individual susceptibility factors on the genotoxic effects of urban air pollution in 106 nonsmoking bus drivers and 101 postal workers in the Copenhagen metropolitan area. We used the frequency of chromosomal aberrations in peripheral blood lymphocytes as a biomar......We have studied the influence of individual susceptibility factors on the genotoxic effects of urban air pollution in 106 nonsmoking bus drivers and 101 postal workers in the Copenhagen metropolitan area. We used the frequency of chromosomal aberrations in peripheral blood lymphocytes...... that long-term exposure to urban air pollution (with traffic as the main contributor) induces chromosome damage in human somatic cells. Low DNA repair capacity and GSTM1 and NAT2 variants associated with reduced detoxification ability increase susceptibility to such damage. The effect of the GSTM1 genotype......, which was observed only in the bus drivers, appears to be associated with air pollution, whereas the NAT2 genotype effect, which affected all subjects, may influence the individual response to some other common exposure or the baseline level of chromosomal aberrations....

  16. Effect of vitamin D3 supplementation and influence of BsmI polymorphism of the VDR gene of the inflammatory profile and oxidative stress in elderly women with vitamin D insufficiency: Vitamin D3 megadose reduces inflammatory markers.

    Science.gov (United States)

    de Medeiros Cavalcante, Isa Gabriela; Silva, Alexandre Sérgio; Costa, Maria José Carvalho; Persuhn, Darlene Camati; Issa, Chahira Taha Mahd Ibrahim; Issa, ChariraTahaMad Ibraim; de Luna Freire, Tiago Lima; da Conceição Rodrigues Gonçalves, Maria

    2015-06-01

    This study aimed to evaluate the effect of vitamin D3 megadose supplementation and influence of BsmI polymorphism in the VDR gene on the inflammatory profile and oxidative stress in elderly women with vitamin D deficiency. A double blind, randomized, placebo-controlled trial was conducted with 40 elderly women (aged 68±6 years) diagnosed with vitamin D insufficiency (24.7±3.1 ng/mL). Participants were distributed into a supplementation group that received 200,000 IU of vitamin D3 (SG; n=20) and a placebo group (PG; n=20). Blood samples were collected at baseline and after intervention to analyse the 25(OH)D, parathyroid hormone, serum calcium, ultra-sensitive C-reactive protein (us-CRP), alpha 1-acid glycoprotein (AGP-A), total antioxidant capacity (TAC), and malondialdehyde (MDA) levels, as well as the renal and hepatic function, and genotyping was performed for BsmI polymorphism. Four weeks after supplementation, elderly women in the SG group showed a significant increase in the serum concentration of 25(OH)D (25.29±2.8 to 31.48±6.0; p=0.0001), which was followed by increased TAC (65.25±15.66 to 71.83±10.71; p=0.03) and decreased serum PTH (46.32±13.2 to 35.45±11.0; p=0.009), us-CRP (0.38±0.3 to 0.19±0.1; p=0.007) and AGP-A levels (75.3±15.4 to 61.1±5.9; p=0.005). Changes in BP, ANAC and MDA were not observed. The 25(OH)D and PTH, us-CRP and AGP-A levels of participants with the BB/Bb genotype were more responsive to supplementation, but their other markers did not change. Supplementation with a vitamin D3 megadose reduced inflammatory markers and increased the total antioxidant capacity in elderly women with vitamin D insufficiency. The 25(OH)D, PTH, us-CRP and AGP-A levels of elderly patients with the BB/Bb genotype were more responsive to supplementation compared with those with the bb genotype. Copyright © 2015 Elsevier Inc. All rights reserved.

  17. The influence of lysozyme on mannitol polymorphism in freeze-dried and spray-dried formulations depends on the selection of the drying process

    DEFF Research Database (Denmark)

    Grohganz, Holger; Lee, Yan-Ying; Rantanen, Jukka

    2013-01-01

    Freeze-drying and spray-drying are often applied drying techniques for biopharmaceutical formulations. The formation of different solid forms upon drying is often dependent on the complex interplay between excipient selection and process parameters. The purpose of this study was to investigate...... the influence of the chosen drying method on the solid state form. Mannitol-lysozyme solutions of 20mg/mL, with the amount of lysozyme varying between 2.5% and 50% (w/w) of total solid content, were freeze-dried and spray-dried, respectively. The resulting solid state of mannitol was analysed by near......-dried formulations an increase in protein concentration resulted in a shift from ß-mannitol to a-mannitol. An increase in final drying temperature of the freeze-drying process towards the temperature of the spray-drying process did not lead to significant changes. It can thus be concluded that it is the drying...

  18. The influence of social structure on brood survival and development in a socially polymorphic ant: insights from a cross-fostering experiment.

    Science.gov (United States)

    Purcell, Jessica; Chapuisat, M

    2012-11-01

    Animal societies vary in the number of breeders per group, which affects many socially and ecologically relevant traits. In several social insect species, including our study species Formica selysi, the presence of either one or multiple reproducing females per colony is generally associated with differences in a suite of traits such as the body size of individuals. However, the proximate mechanisms and ontogenetic processes generating such differences between social structures are poorly known. Here, we cross-fostered eggs originating from single-queen (= monogynous) or multiple-queen (= polygynous) colonies into experimental groups of workers from each social structure to investigate whether differences in offspring survival, development time and body size are shaped by the genotype and/or prefoster maternal effects present in the eggs, or by the social origin of the rearing workers. Eggs produced by polygynous queens were more likely to survive to adulthood than eggs from monogynous queens, regardless of the social origin of the rearing workers. However, brood from monogynous queens grew faster than brood from polygynous queens. The social origin of the rearing workers influenced the probability of brood survival, with workers from monogynous colonies rearing more brood to adulthood than workers from polygynous colonies. The social origin of eggs or rearing workers had no significant effect on the head size of the resulting workers in our standardized laboratory conditions. Overall, the social backgrounds of the parents and of the rearing workers appear to shape distinct survival and developmental traits of ant brood. © 2012 The Authors. Journal of Evolutionary Biology © 2012 European Society For Evolutionary Biology.

  19. Polymorphs of Pridopidine Hydrochloride

    DEFF Research Database (Denmark)

    Zimmermann, A.; Frostrup, B.; Bond, A. D.

    2012-01-01

    of both polymorphs contain N+-H center dot center dot center dot Cl-center dot center dot center dot N+-H center dot center dot center dot interactions, and the polymorphism can be viewed as alternative orientations (parallel or antiparallel) of comparable molecular columns while retaining the center dot...... center dot center dot N+-H center dot center dot center dot Cl-center dot center dot center dot N+-H center dot center dot center dot motif between columns. Forms I and II have melting points of 199 and 210 degrees C, respectively. Following melting of form I, a kinetically controlled crystallization...

  20. The Serotonin Transporter Gene Polymorphisms and Risk of Ischemic Stroke

    DEFF Research Database (Denmark)

    Mortensen, Janne Kærgård; Kraglund, Kristian Lundsgaard; Johnsen, Søren Paaske

    2018-01-01

    may influence platelet activity, as they result in different levels of transporters and thereby different levels of serotonin in platelets. SERT gene polymorphisms have thus been associated with the risk of myocardial infarction. A similar association may exist between SERT gene polymorphisms...... and stroke. However, to our knowledge, this potential association has not previously been studied. We therefore aimed to investigate the association between polymorphisms in the SERT gene and the risk of ischemic stroke/transitory ischemic attack (TIA). MATERIALS AND METHODS: We conducted a case...

  1. GENETIC VARIATION IN THE BETA-3-ADRENORECEPTOR GENE (TRP64ARG POLYMORPHISM) AND THEIR INFLUENCE ON ANTHROPOMETRIC PARAMETERS AND INSULIN RESISTANCE AFTER A HIGH PROTEIN/LOW CARBOHYDRATE VERSUS A STANDARD HYPOCALORIC DIET.

    Science.gov (United States)

    de Luis, Daniel Antonio; Aller, Rocío; Izaola, Olatz; de la Fuente, Beatriz; Romero, Enrique

    2015-08-01

    the Trp64Arg variant in Beta receptor has been reported to be associated with increased body weight and insulin resistance Objective: the aim of our study was to investigate the influence of polymorphism (rs 4994) in Beta-3-adrenergic receptor gene on metabolic response and weight loss in a medium-term intervention study secondary's to a high protein/low carbohydrate vs. a standard hypocaloric diets (1000 kcal/day). a population of 284 obese subjects was analyzed in a randomized trial. A nutritional evaluation was performed at the beginning and at the end of a 9-month period in which subjects received 1 of 2 diets (diet HP: high protein/low carbohydrate vs diet S: standard diet). there were no significant differences between the positive effects (on weight, BMI, waist circumference, fat mass, systolic blood pressure and leptin levels) in either genotype group with both diets. With both diets and only in wild genotype (diet HP vs diet S), total cholesterol (-10.1 ± 3.9 mg/dl vs -10.1 ± 2.2 mg/dl;p>0.05), LDL cholesterol (-9.5 ± 2.1 mg/dl vs -8.5 ± 2.3 mg/dl;p>0.05) and triglycerides (-19.1 ± 2.1 mg/dl vs -14.3 ± 2.1 mg/dl;p>0.05) decreased. The improvement in these parameters was similar in subjects with diet HP than HS. With diet HP and only in wild genotype, insulin levels (-3.7 ± 1.9 UI/L;phypocaloric diets is the greatest in subjects with normal homozygous beta 3-AR gene. Improvement in total cholesterol, LDL-cholesterol, triglyceride, glucose, insulin and HOMA-R levels is better than in the heterozygous group. Copyright AULA MEDICA EDICIONES 2014. Published by AULA MEDICA. All rights reserved.

  2. Association of SSTR2 Polymorphisms and Glucose Homeostasis Phenotypes

    OpenAIRE

    Sutton, Beth S.; Palmer, Nicholette D.; Langefeld, Carl D.; Xue, Bingzhong; Proctor, Alexandria; Ziegler, Julie T.; Haffner, Steven M.; Norris, Jill M.; Bowden, Donald W.

    2009-01-01

    OBJECTIVE This study evaluated the influence of somatostatin receptor type 2 (SSTR2) polymorphisms on measures of glucose homeostasis in the Insulin Resistance Atherosclerosis Family Study (IRASFS). SSTR2 is a G-protein?coupled receptor that, in response to somatostatin, mediates inhibition of insulin, glucagon, and growth hormone release and thus may affect glucose homeostasis. RESEARCH DESIGN AND METHODS Ten single nucleotide polymorphisms (SNPs) spanning the gene were chosen using a SNP de...

  3. Teaching polymorphism early

    DEFF Research Database (Denmark)

    2005-01-01

    Is it possible to teach dynamic polymorphism early? What techniques could facilitate teaching it in Java. This panel will bring together people who have considered this question and attempted to implement it in various ways, some more completely than others. It will also give participants...

  4. Independent and combined influence of the FTO rs9939609 and MC4Rrs17782313 polymorphisms on hypocaloric diet induced changes in body mass and composition and energy metabolism in non-morbid obese premenopausal women.

    Science.gov (United States)

    Labayen, Idoia; Margareto, Javier; Maldonado-Martin, Sara; Gorostegi, Ilargi; Illera, Maitane; Medrano, María; Barrenechea, Lurdes; Larrarte, Eider

    2015-05-01

    To examine the independent and combined influence of the FTOrs9939609 and the MC4Rrs17782313 polymorphisms on changes in fat mass (FM), resting energy expenditure (REE), leptin, and thyrotropin (TSH) levels, after a 12-week energy-restricted diet intervention in non-morbid premenopausal obese women. Fat mass (dual X-ray absorptiometry), REE (indirect calorimetry) and plasma leptin and thyrotropin levels were measured (before and after the intervention) in 77 obese (BMI: 33.9 ± 2.8 kg/m(2)) women (age: 36.8 ± 7.0y). There were no significant differences across FTOrs9939609 genotype groups (TT vs. A allele carriers, Ps>0.1) on changes in body mass (-8.6 ± 3.2% vs. -8.7 ± 3.3 %), FM (12.8 ± 4.7% vs. -12.9 ± 6.3%), REE (-11.3 ± 4.7 vs. -9.4 ± 8.1%), leptin (-34.1 ± 25.1% vs. -43.5 ± 24.1%) or TSH (5.2 ± 34.5% vs. -1.7 ± 27.1%) levels. Moreover, it was not observed any significant difference on changes in body mass (-8.6 ± 3.6% vs. -8.9 ± 2.6%), FM (-12.7 ± 6.1% vs. -13.4 ± 5.3%), REE (-9.8 ± 7.4% -9.4 ± 9.4%), leptin (-39.0 ± 26.9% vs. -44.8 ± 18.4%) or TSH (-1.0 ± 30.0% vs. 1.5 ± 26.5%) levels between non-C allele carriers and C allele carriers of the MC4Rrs17782313 (Ps>0.3). Finally, there were no significant difference on changes in body mass and composition, REE, leptin or TSH levels among non-risk allele carriers, carriers of the C allele risk of the MC4Rrs17782313, carriers of the A allele of the FTOrs9939609 and carriers of both risk alleles after the 12-week energy-restricted diet intervention (Ps>0.1). Carrying the A risk allele of the FTOrs9939609 and/or the C risk allele of the MC4Rrs17782313 did not influence body mass and FM loss, or REE decrease in obese women after a 12-week energy-restricted diet intervention. Copyright AULA MEDICA EDICIONES 2014. Published by AULA MEDICA. All rights reserved.

  5. β2-adrenergic receptor Thr164Ile polymorphism, obesity, and diabetes

    DEFF Research Database (Denmark)

    Thomsen, Mette; Dahl, Morten; Tybjærg-Hansen, Anne

    2012-01-01

    The β(2)-adrenergic receptor (ADRB2) influences regulation of energy balance by stimulating catecholamine-induced lipolysis in adipose tissue. The rare functional ADRB2rs1800888(Thr164Ile) polymorphism could therefore influence risk of obesity and subsequently diabetes.......The β(2)-adrenergic receptor (ADRB2) influences regulation of energy balance by stimulating catecholamine-induced lipolysis in adipose tissue. The rare functional ADRB2rs1800888(Thr164Ile) polymorphism could therefore influence risk of obesity and subsequently diabetes....

  6. Influence of thiopurine methyltransferase gene polymorphism on ...

    Indian Academy of Sciences (India)

    Azza A. G. Tantawy

    2017-11-28

    Nov 28, 2017 ... Thirty-two patients were on maintenance and another 32 completed their chemotherapy. .... hepatitis and liver function tests, ALT and AST were recorded. ... C with or without neutropenia. Decrease absolute neutrophil count.

  7. Does colour polymorphism enhance survival of prey populations?

    Science.gov (United States)

    Wennersten, Lena; Forsman, Anders

    2009-01-01

    That colour polymorphism may protect prey populations from predation is an old but rarely tested hypothesis. We examine whether colour polymorphic populations of prey exposed to avian predators in an ecologically valid visual context were exposed to increased extinction risk compared with monomorphic populations. We made 2976 artificial pastry prey, resembling Lepidoptera larvae, in four different colours and presented them in 124 monomorphic and 124 tetramorphic populations on tree trunks and branches such that they would be exposed to predation by free-living birds, and monitored their ‘survival’. Among monomorphic populations, there was a significant effect of prey coloration on survival, confirming that coloration influenced susceptibility to visually oriented predators. Survival of polymorphic populations was inferior to that of monomorphic green populations, but did not differ significantly from monomorphic brown, yellow or red populations. Differences in survival within polymorphic populations paralleled those seen among monomorphic populations; the red morph most frequently went extinct first and the green morph most frequently survived the longest. Our findings do not support the traditional protective polymorphism hypothesis and are in conflict with those of earlier studies. As a possible explanation to our findings, we offer a competing ‘giveaway cue’ hypothesis: that polymorphic populations may include one morph that attracts the attention of predators and that polymorphic populations therefore may suffer increased predation compared with some monomorphic populations. PMID:19324729

  8. Single Nucleotide Polymorphism

    DEFF Research Database (Denmark)

    Børsting, Claus; Pereira, Vania; Andersen, Jeppe Dyrberg

    2014-01-01

    Single nucleotide polymorphisms (SNPs) are the most frequent DNA sequence variations in the genome. They have been studied extensively in the last decade with various purposes in mind. In this chapter, we will discuss the advantages and disadvantages of using SNPs for human identification...... of SNPs. This will allow acquisition of more information from the sample materials and open up for new possibilities as well as new challenges....

  9. Influence on serum asymmetric dimethylarginine (ADMA) concentrations of human paraoxonase 1 polymorphism (Q192R) and exposure to polycyclic aromatic hydrocarbons (PAHs) in Mexican women, a gene-environment interaction.

    Science.gov (United States)

    Ochoa-Martínez, Ángeles C; Ruíz-Vera, Tania; Almendarez-Reyna, Claudia I; Orta-García, Sandra T; Pérez-Maldonado, Iván N

    2017-11-01

    It has been demonstrated that Cardiovascular Diseases (CVD) are a consequence of the combination of genetic and environmental factors and/or the interaction between them. Therefore, the aim of this study was to evaluate the impact of polycyclic aromatic hydrocarbon (PAHs) exposure and PON1 Q192R polymorphism (genetic susceptibility) on serum asymmetric dimethylarginine (ADMA) levels in Mexican women (n = 206). Urinary 1-hydroxypyrene concentrations (1-OHP; exposure biomarker for PAHs) were quantified using a high-performance liquid chromatography technique, PON1 Q192R polymorphism was genotyped using TaqMan probes and serum ADMA concentrations were evaluated using a commercially available ELISA kit. Urinary 1-OHP levels detected in this study ranged from 0.07 to 9.37 μmol/mol of creatinine (0.13-18.0 μg/g of creatinine). Regarding allele frequency (PON1 Q192R polymorphism), the 192Q-allele frequency was 0.43 and for the 192R-allele it was 0.57. In relation to serum ADMA levels, the levels ranged from 0.06 to 1.46 μmol/L. Moreover, multiple linear regression analysis was performed and associations between urinary 1-OHP levels (β = 0.05, p = 0.002), PON1 Q192R polymorphism (β = 0.04, p = 0.003) and serum ADMA concentrations were found. Besides, an interaction (gene-environment interaction) of both independent variables (1-OHP and PON1 polymorphism) on serum ADMA levels was found (β = 0.04, p = 0.02) in the constructed multiple linear model. Therefore, according to the significance of this research, it is necessary to execute health programs to reduce cardiovascular risk in the assessed population. Copyright © 2017 Elsevier Ltd. All rights reserved.

  10. Polymorphisms of the LEP- and LEPR Gene and Obesity in Patients Using Antipsychotic Medication

    NARCIS (Netherlands)

    Gregoor, Jochem G.; van der Weide, Jan; Mulder, Hans; Cohen, Dan; van Megen, Harold J. G. M.; Egberts, Antoine C. G.; Heerdink, Eibert R.

    Weight gain is one of the most serious adverse effects of atypical antipsychotic agents. Genetic factors influence the risk of an individual to gain weight. The objective of our study was to determine whether the LEPR Q223R polymorphism and the LEP promoter 2548G/ A polymorphism are associated with

  11. The effects of selecting for the myostatin F94L polymorphism on reproductive traits in pubertal heifers

    Science.gov (United States)

    The myostatin F94L polymorphism influences carcass traits in steers; however, the influence of this polymorphism on female reproductive performance should be characterized as part of using it for marker assisted selection. Results from USMARC indicate that heifers that are homozygous for the L allel...

  12. [The influence of STAT4 rs7574865 (G/T) polymorphism on the risk of clinical and immunological phenotypes of systemic sclerosis in a Russian patient population: Results of a pilot study].

    Science.gov (United States)

    Krylov, M Yu; Ananyeva, L P; Koneva, О А; Starovoytova, M N; Desinova, O V; Ovsyannikova, O B; Aleksandrova, E N; Novikov, A A; Guseva, I A; Konovalova, N V; Varlamov, D A

    To examine the association of signal transducer and activator transcription 4 (STAT4) rs7574865 G/T polymorphism with a predisposition to systemic sclerosis (SSC) and associated clinical and autoimmune phenotypes in a Russian population. A total of 102 patients with SSC and 103 healthy individuals as controls were examined. STAT4 rs7574865 polymorphism was investigated by real-time polymerase chain reaction. The carriers of the T allele showed a statistically significant association with SSC, a diffuse form (DF), the presence of interstitial lung disease (ILD), cardiac injury (CI), and seropositivity for anti-topoisomerase I antibodies (ATA). The findings results confirm the important role of STAT4 gene in the predisposition to SSC and its phenotypes, such as DF, ILD, CI, and ATA in the Russian population.

  13. Diffuse Scattering as an Aid to the Understanding of Polymorphism in Pharmaceuticals

    Energy Technology Data Exchange (ETDEWEB)

    Welberry, T.R.; Chan, E.J.; Goossens, D.J.; Heerdegen, A.P. (ANU)

    2012-04-30

    Polymorphism occurs when the same molecular compound can crystallize in more than one distinct crystal structure. Its study is a field of great interest and activity. This is largely driven by its importance in the pharmaceutical industry, but polymorphism is also an issue in the pigments, dyes, and explosives industries. The polymorph formed by a compound generally exerts a strong influence on its solid-state properties. The polymorphic form of a drug molecule may affect the ease of manufacture and processing, shelf life, and most significantly the rate of uptake of the molecule by the human body. They can even vary in toxicity; one polymorph may be safe, while a second may be toxic. In this review of recently published work, we show how diffuse scattering experiments coupled with Monte Carlo (MC) computer modeling can aid in the understanding of polymorphism. Examples of the two common pharmaceuticals, benzocaine and aspirin, both of which are bimorphic, at ambient temperatures, are discussed.

  14. Genetic variation in the cannabinoid receptor gene (CNR1) (G1359A polymorphism) and their influence on anthropometric parameters and metabolic parameters under a high monounsaturated vs. high polyunsaturated fat hypocaloric diets.

    Science.gov (United States)

    de Luis, Daniel Antonio; Aller, Rocio; Gonzalez Sagrado, Manuel; Conde, Rosa; Izaola, Olatz; de la Fuente, Beatriz

    2013-08-01

    An intragenic polymorphism (1359 G/A) of the cannabinoid receptor 1 (CNR1) gene was reported as a common polymorphism in Caucasian populations (rs1049353). Intervention studies with this polymorphism have yield contradictories results. We decide to investigate the role of polymorphism (G1359A) of (CNR1) gene on metabolic parameters and weight loss secondary to a high monounsaturated fat and high polyunsaturated fat hypocaloric diets in obese subjects. A population of 258 obese subjects was analyzed in a randomized trial. A nutritional evaluation was performed at the beginning and at the end of a 3-month period in which subjects received 1 of 2 diets (diet M: high monounsaturated fat diet vs diet P: high polyunsaturated fat diet). One hundred and sixty five patients (63.9%) had the genotype G1359G and 93 (36.1%) patients (A allele carriers) had G1359A (78 patients,30.3%) or A1359A (15 patients,5.8%) genotypes. In subjects with both genotypes, body mass index, weight, fat mass, waist circumference and systolic blood pressures decreased with both diets. With the diet-type M and in both genotype groups, biochemical parameters remained unchanged. After the diet type P and in subjects with both genotypes, glucose, total cholesterol, low-density lipoprotein (LDL) cholesterol, insulin and homeostasis model assessment for insulin resistance (HOMA-IR) levels decreased. In G1359G genotype subjects after both diets, leptin levels decreased. The finding of this study is the association of the A allele with a lack of improvement on leptin levels. Subjects with both genotypes and after a high polyunsaturated fat hypocaloric diet showed a significant improvement of LDL cholesterol, total cholesterol, HOMA-IR and insulin levels. Copyright © 2013 Elsevier Inc. All rights reserved.

  15. Inflammatory Gene Polymorphisms in Lung Cancer Susceptibility.

    Science.gov (United States)

    Eaton, Keith D; Romine, Perrin E; Goodman, Gary E; Thornquist, Mark D; Barnett, Matt J; Petersdorf, Effie W

    2018-05-01

    Chronic inflammation has been implicated in carcinogenesis, with increasing evidence of its role in lung cancer. We aimed to evaluate the role of genetic polymorphisms in inflammation-related genes in the risk for development of lung cancer. A nested case-control study design was used, and 625 cases and 625 well-matched controls were selected from participants in the β-Carotene and Retinol Efficacy Trial, which is a large, prospective lung cancer chemoprevention trial. The association between lung cancer incidence and survival and 23 polymorphisms descriptive of 11 inflammation-related genes (interferon gamma gene [IFNG], interleukin 10 gene [IL10], interleukin 1 alpha gene [IL1A], interleukin 1 beta gene [IL1B], interleukin 2 gene [IL2], interleukin 4 receptor gene [IL4R], interleukin 4 gene [IL4], interleukin 6 gene [IL6], prostaglandin-endoperoxide synthase 2 gene [PTGS2] (also known as COX2), transforming growth factor beta 1 gene [TGFB1], and tumor necrosis factor alpha gene [TNFA]) was evaluated. Of the 23 polymorphisms, two were associated with risk for lung cancer. Compared with individuals with the wild-type (CC) variant, individuals carrying the minor allele variants of the IL-1β-511C>T promoter polymorphism (rs16944) (CT and TT) had decreased odds of lung cancer (OR = 0.74, [95% confidence interval (CI): 0.58-0.94] and OR = 0.71 [95% CI: 0.50-1.01], respectively, p = 0.03). Similar results were observed for the IL-1β-1464 C>G promoter polymorphism (rs1143623), with presence of the minor variants CG and CC having decreased odds of lung cancer (OR = 0.75 [95% CI: 0.59-0.95] and OR = 0.69 [95% CI: 0.46-1.03], respectively, p = 0.03). Survival was not influenced by genotype. This study provides further evidence that IL1B promoter polymorphisms may modulate the risk for development of lung cancer. Copyright © 2018 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.

  16. 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.

    Science.gov (United States)

    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.

  17. Prevalence of thrombophilic gene polymorphisms (FVL G1691A and ...

    African Journals Online (AJOL)

    Hamdia Ezzat

    2014-02-22

    Feb 22, 2014 ... The Egyptian Journal of Medical Human Genetics www.ejmhg.eg.net ... on polymorphisms influencing some biological functions [8]. Among the candidate ...... 2005;3(2):292–9. [17] Graham I, Atar D, Borch-Johnsen K, et al.

  18. cDNA cloning and polymorphic domains of the major ...

    African Journals Online (AJOL)

    Analysis of the phylogenetic tree indicated no relationship between the breeds and polymorphic alleles. All these results therefore indicate that MHC I class molecule of domestic chickens was more influenced by the pressure of common pathogens rather than geographic differences. Key words: Chinese native chicken, ...

  19. cDNA cloning and polymorphic domains of the major ...

    African Journals Online (AJOL)

    Jane

    2011-10-24

    Oct 24, 2011 ... phylogenetic tree indicated no relationship between the breeds and polymorphic alleles. All these results therefore indicate that MHC I class molecule of domestic chickens was more influenced by the pressure of common pathogens rather than geographic differences. Key words: Chinese native chicken, ...

  20. Bistetracene Thin Film Polymorphic Control to Unravel the Effect of Molecular Packing on Charge Transport

    KAUST Repository

    Burnett, Edmund K.

    2018-02-26

    Polymorphism, the ability for a given material to adopt multiple crystalline packing states, is a powerful approach for investigating how changes in molecular packing influence charge transport within organic semiconductors. In this study, a new

  1. Bistetracene Thin Film Polymorphic Control to Unravel the Effect of Molecular Packing on Charge Transport

    KAUST Repository

    Burnett, Edmund K.; Ly, Jack; Niazi, Muhammad Rizwan; Zhang, Lei; McCuskey, Samantha R.; Amassian, Aram; Smilgies, Detlef-M.; Mannsfeld, Stefan C. B.; Briseno, Alejandro L.

    2018-01-01

    Polymorphism, the ability for a given material to adopt multiple crystalline packing states, is a powerful approach for investigating how changes in molecular packing influence charge transport within organic semiconductors. In this study, a new

  2. Association of Lactase 13910 C/T polymorphism with bone mineral ...

    Indian Academy of Sciences (India)

    Navya

    2017-03-24

    Mar 24, 2017 ... polymorphism with bone mineral density (BMD) and fracture risk, but previous results have been inconclusive ... Although osteoporosis and fracture are influenced by many environmental factors such ... Materials and Methods.

  3. Xmn1 Polymorphism in Sickle cell trait cohort in Siwa Oasis

    Indian Academy of Sciences (India)

    Dr Pacint Moez

    were obtained from parents of all recruited children, before participation, in the presence of a doctor and a .... cell patients was greatly influenced by the Xmn1 polymorphism. .... Life expectancy and risk factors for early death. N. Engl. J. Med.

  4. Polymorphic Evolutionary Games.

    Science.gov (United States)

    Fishman, Michael A

    2016-06-07

    In this paper, I present an analytical framework for polymorphic evolutionary games suitable for explicitly modeling evolutionary processes in diploid populations with sexual reproduction. The principal aspect of the proposed approach is adding diploid genetics cum sexual recombination to a traditional evolutionary game, and switching from phenotypes to haplotypes as the new game׳s pure strategies. Here, the relevant pure strategy׳s payoffs derived by summing the payoffs of all the phenotypes capable of producing gametes containing that particular haplotype weighted by the pertinent probabilities. The resulting game is structurally identical to the familiar Evolutionary Games with non-linear pure strategy payoffs (Hofbauer and Sigmund, 1998. Cambridge University Press), and can be analyzed in terms of an established analytical framework for such games. And these results can be translated into the terms of genotypic, and whence, phenotypic evolutionary stability pertinent to the original game. Copyright © 2016 Elsevier Ltd. All rights reserved.

  5. Depressive symptoms in schizophrenia and dopamine and serotonin gene polymorphisms.

    Science.gov (United States)

    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.

  6. Influence of the CCR2-V64I Polymorphism on Human Immunodeficiency Virus Type 1 Coreceptor Activity and on Chemokine Receptor Function of CCR2b, CCR3, CCR5, and CXCR4

    OpenAIRE

    Lee, Benhur; Doranz, Benjamin J.; Rana, Shalini; Yi, Yanji; Mellado, Mario; Frade, Jose M. R.; Martinez-A., Carlos; O’Brien, Stephen J.; Dean, Michael; Collman, Ronald G.; Doms, Robert W.

    1998-01-01

    The chemokine receptors CCR5 and CXCR4 are used by human immunodeficiency virus type 1 (HIV-1) in conjunction with CD4 to infect cells. In addition, some virus strains can use alternative chemokine receptors, including CCR2b and CCR3, for infection. A polymorphism in CCR2 (CCR2-V64I) is associated with a 2- to 4-year delay in the progression to AIDS. To investigate the mechanism of this protective effect, we studied the expression of CCR2b and CCR2b-V64I, their chemokine and HIV-1 coreceptor ...

  7. Genetic Analysis of the Atrial Natriuretic Peptide Gene Polymorphisms among Essential Hypertensive Patients in Malaysia

    Directory of Open Access Journals (Sweden)

    Nooshin Ghodsian

    2016-01-01

    Full Text Available Background. Atrial natriuretic peptide (ANP considerably influences blood pressure regulation through water and sodium homoeostasis. Several of the studies have utilized anonymous genetic polymorphic markers and made inconsequent claims about the ANP relevant disorders. Thus, we screened Insertion/Deletion (ID and G191A polymorphisms of ANP to discover sequence variations with potential functional significance and to specify the linkage disequilibrium pattern between polymorphisms. The relationships of detected polymorphisms with EH with or without Type 2 Diabetes Mellitus (T2DM status were tested subsequently. Method. ANP gene polymorphisms (I/D and A191G were specified utilizing mutagenically separated Polymerase Chain Reaction (PCR in 320 subjects including 163 EH case subjects and 157 controls. Result. This case-control study discovered a significant association between I/D polymorphisms of ANP gene in EH patient without T2DM. However, the study determined no association between G191A polymorphisms of ANP in EH with or without T2DM. In addition, sociodemographic factors in the case and healthy subjects exhibited strong differences (P<0.05. Conclusion. As a risk factor, ANP gene polymorphisms may affect hypertension. Despite the small sample size in this study, it is the first research assessing the ANP gene polymorphisms in both EH and T2DM patients among Malaysian population.

  8. Polymorphisms associated with ventricular tachyarrhythmias: rationale, design, and endpoints of the 'diagnostic data influence on disease management and relation of genomics to ventricular tachyarrhythmias in implantable cardioverter/defibrillator patients (DISCOVERY)' study

    DEFF Research Database (Denmark)

    Wieneke, Heinrich; Spencker, Sebastian; Svendsen, Jesper Hastrup

    2010-01-01

    Implantable cardioverter-defibrillator (ICD) therapy is effective in primary and secondary prevention for patients who are at high risk of sudden cardiac death. However, the current risk stratification of patients who may benefit from this therapy is unsatisfactory. Single nucleotide polymorphism...... pathways will be investigated. As it is a diagnostic study, DISCOVERY will also investigate the impact of long-term device diagnostic data on the management of patients suffering from chronic cardiac disease as well as medical decisions made regarding their treatment.......Implantable cardioverter-defibrillator (ICD) therapy is effective in primary and secondary prevention for patients who are at high risk of sudden cardiac death. However, the current risk stratification of patients who may benefit from this therapy is unsatisfactory. Single nucleotide polymorphisms...... modulate the risk for arrhythmias and sudden cardiac death, and identification of common variants could help to better identify patients at risk. The DISCOVERY study is an interventional, longitudinal, prospective, multi-centre diagnostic study that will enrol 1287 patients in approximately 80 European...

  9. A monoclinic polymorph of theophylline

    Directory of Open Access Journals (Sweden)

    Shuo Zhang

    2011-12-01

    Full Text Available A monoclinic polymorph of theophylline, C7H8N4O2, has been obtained from a chloroform/methanol mixture by evaporation under ambient conditions. The new polymorph crystallizes with two molecules in the asymmetric unit. The structure features intermolecular N—H...O hydrogen bonds, resulting in the formation of dimers between two crystallographically different molecules; each molecule acts as both donor and acceptor.

  10. A new multiplex PCR strategy for the simultaneous determination of four genetic polymorphisms affecting HIV-1 disease progression

    DEFF Research Database (Denmark)

    Kristiansen, Thomas Birk; Knudsen, Troels Bygum; Ohlendorff, Stine Dahl

    2001-01-01

    The CCR5 Delta32, CCR2 64I, SDF1 3'A, and CCR5 promoter 59029 polymorphisms have been suggested to influence HIV-1 disease progression. Furthermore, the CCR5 Delta32 and the CCR2 64I polymorphisms have been associated with various other diseases. The purpose of the present study was to develop......, SDF1 3'A, and CCR5 promoter 59029 A/G polymorphisms....

  11. Matrix metalloproteinase gene polymorphisms in patients with coronary artery disease

    Directory of Open Access Journals (Sweden)

    Vanessa L.N. Dalepiane

    2007-01-01

    Full Text Available Matrix metalloproteinases (MMPs play an important role in the pathogenesis of atherosclerosis, the pathology underlying the majority of coronary artery disease (CAD. In this study we tested the hypothesis that polymorphic variation in the MMP genes influences the risk of developing atherosclerosis. We analyzed functional polymorphisms in the promoter of the MMP-1, MMP-3, MMP-9 and MMP-12 genes in 183 Brazilian Caucasian individuals submitted to coronary angiography, of which 67 (37% had normal coronary arteries (control group and 116 (63% had CAD (CAD patient group. The -1607 1G/2G MMP-1, -1171 5A/6A MMP-3, -1562 C/T MMP-9, -82 A/G MMP-12 polymorphisms were analyzed by PCR followed by restriction digestion. No significant differences were observed in allele frequencies between the CAD patients and controls. Haplotype analysis showed no differences between the CAD patients and controls. There was a significant difference in the severity of CAD, as assessed by the number of diseased vessels, in MMP-1 1G/1G homozygous individuals and in those homozygous for the 6A allele of the MMP-3 polymorphism. However, multivariate analysis showed that diabetes mellitus was the only variable independently associated with CAD severity. Our findings indicated that MMP polymorphisms have no significant impact on the risk and severity of CAD.

  12. New polymorphous computing fabric

    International Nuclear Information System (INIS)

    Wolinski, Christophe; Gokhale, Maya; McCabe, Kevin P.

    2002-01-01

    This paper introduces a new polymorphous computing Fabric well suited to DSP and Image Processing and describes its implementation on a Configurable System on a Chip (CSOC). The architecture is highly parameterized and enables customization of the synthesized Fabric to achieve high performance for a specific class of application. For this reason it can be considered to be a generic model for hardware accelerator synthesis from a high level specification. Another important innovation is the Fabric uses a global memory concept, which gives the host processor random access to all the variables and instructions on the Fabric. The Fabric supports different computing models including MIMD, SPMD and systolic flow and permits dynamic reconfiguration. We present a specific implementation of a bank of FIR filters on a Fabric composed of 52 cells on the Altera Excalibur ARM running at 33 MHz. The theoretical performance of this Fabric is 1.8 GMACh. For the FIR application we obtain 1.6 GMAC/s real performance. Some automatic tools have been developed like the tool to provide a host access utility and assembler.

  13. Association of MMP7 -181A→G Promoter Polymorphism with Gastric Cancer Risk: INFLUENCE OF NICOTINE IN DIFFERENTIAL ALLELE-SPECIFIC TRANSCRIPTION VIA INCREASED PHOSPHORYLATION OF cAMP-RESPONSE ELEMENT-BINDING PROTEIN (CREB).

    Science.gov (United States)

    Kesh, Kousik; Subramanian, Lakshmi; Ghosh, Nillu; Gupta, Vinayak; Gupta, Arnab; Bhattacharya, Samir; Mahapatra, Nitish R; Swarnakar, Snehasikta

    2015-06-05

    Elevated expression of matrix metalloproteinase7 (MMP7) has been demonstrated to play a pivotal role in cancer invasion. The -181A→G (rs11568818) polymorphism in the MMP7 promoter modulates gene expression and possibly affects cancer progression. Here, we evaluated the impact of -181A→G polymorphism on MMP7 promoter activity and its association with gastric cancer risk in eastern Indian case-control cohorts (n = 520). The GG genotype as compared with the AA genotype was predisposed (p = 0.02; odds ratio = 1.9, 95% confidence interval = 1.1-3.3) to gastric cancer risk. Stratification analysis showed that tobacco addiction enhanced gastric cancer risk in GG subjects when compared with AA subjects (p = 0.03, odds ratio = 2.46, and 95% confidence interval = 1.07-5.68). Meta-analysis revealed that tobacco enhanced the risk for cancer more markedly in AG and GG carriers. Activity and expression of MMP7 were significantly higher in GG than in AA carriers. In support, MMP7 promoter-reporter assays showed greater transcriptional activity toward A to G transition under basal/nicotine-induced/cAMP-response element-binding protein (CREB) overexpressed conditions in gastric adenocarcinoma cells. Moreover, nicotine (a major component of tobacco) treatment significantly up-regulated MMP7 expression due to enhanced CREB phosphorylation followed by its nuclear translocation in gastric adenocarcinoma cells. Furthermore, chromatin immunoprecipitation experiments revealed higher binding of phosphorylated CREB with the -181G than the -181A allele. Altogether, specific binding of phosphorylated CREB to the G allele-carrying promoter enhances MMP7 gene expression that is further augmented by nicotine due to increased CREB phosphorylation and thereby increases the risk for gastric cancer. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

  14. 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

  15. PECAM-1 polymorphism affects monocyte adhesion to endothelial cells.

    Science.gov (United States)

    Goodman, Reyna S; Kirton, Christopher M; Oostingh, Gertie J; Schön, Michael P; Clark, Michael R; Bradley, J Andrew; Taylor, Craig J

    2008-02-15

    Platelet endothelial cell adhesion molecule-1 (PECAM-1/CD31) plays an important role in leukocyte-endothelial cell adhesion and transmigration. Single nucleotide polymorphisms of PECAM-1 encoding amino acid substitutions at positions 98 leucine/valine (L/V), 536 serine/asparagine (S/N), and 643 arginine/glycine (R/G) occur in strong genetic linkage resulting in two common haplotypes (LSR and VNG). These PECAM-1 polymorphisms are associated with graft-versus-host disease after hematopoietic stem cell transplantation and with cardiovascular disease, but whether they influence PECAM-1 function is unknown. We examined the effect of homozygous and heterozygous expression of the PECAM-1 LSR and VNG genotypes on the adhesive interactions of peripheral blood monocytes and activated endothelial cell monolayers under shear stress in a flow-based cell adhesion assay. There was no difference in monocyte adhesion between the two homozygous genotypes of PECAM-1 but when monocytes expressed both alleles in heterozygous form, firm adhesion of monocytes to endothelial cells was markedly increased. PECAM-1 polymorphism expressed in homozygous or heterozygous form by endothelial cells did not influence monocyte adhesion. This is, to our knowledge, the first demonstration that PECAM-1 genotype can alter the level of monocyte binding to endothelial cells and a demonstration that heterozygous expression of a polymorphic protein may lead to altered function.

  16. Vitamin D Receptor Gene Polymorphisms Associated with Childhood Autism.

    Science.gov (United States)

    Cieślińska, Anna; Kostyra, Elżbieta; Chwała, Barbara; Moszyńska-Dumara, Małgorzata; Fiedorowicz, Ewa; Teodorowicz, Małgorzata; Savelkoul, Huub F J

    2017-09-09

    Autism spectrum disorder (ASD) is a group of heterogeneous, behaviorally defined disorders whereby currently no biological markers are common to all affected individuals. A deregulated immune response may be contributing to the etiology of ASD. The active metabolite of vitamin D₃ has an immunoregulatory role mediated by binding to the vitamin D receptor (VDR) in monocyte, macrophages, and lymphocytes. The effects of vitamin D and interaction with the VDR may be influenced by polymorphism in the VDR gene. Genetic association of four different VDR polymorphisms (Apa-I, Bsm-I, Taq-I, Fok-I) associated with susceptibility to the development of autism in children was investigated. We uniquely found an association between the presence of the T allele at position Taq-I and presence of the a allele at position Apa-I of the VDR gene with decreased ASD incidence. There was also an association between female gender and the presence of the T allele. We found no statistical significant correlation between VDR single nucleotide polymorphisms (SNPs) and vitamin D₃ concentration in serum of ASD children. Genetic polymorphism in two SNP in VDR may be correlated with development of ASD symptoms by influencing functionality of vitamin D₃ metabolism, while vitamin D₃ levels were not significantly different between ASD and non-ASD children.

  17. 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...

  18. Toll-like receptor polymorphisms in malaria-endemic populations

    Directory of Open Access Journals (Sweden)

    Zimmerman Peter A

    2009-03-01

    Full Text Available Abstract Background Toll-like receptors (TLR and related downstream signaling pathways of innate immunity have been implicated in the pathogenesis of Plasmodium falciparum malaria. Because of their potential role in malaria pathogenesis, polymorphisms in these genes may be under selective pressure in populations where this infectious disease is endemic. Methods A post-PCR Ligation Detection Reaction-Fluorescent Microsphere Assay (LDR-FMA was developed to determine the frequencies of TLR2, TLR4, TLR9, MyD88-Adaptor Like Protein (MAL single nucleotide polymorphisms (SNPs, and TLR2 length polymorphisms in 170 residents of two regions of Kenya where malaria transmission is stable and high (holoendemic or episodic and low, 346 residents of a malaria holoendemic region of Papua New Guinea, and 261 residents of North America of self-identified ethnicity. Results The difference in historical malaria exposure between the two Kenyan sites has significantly increased the frequency of malaria protective alleles glucose-6-phoshpate dehydrogenase (G6PD and Hemoglobin S (HbS in the holoendemic site compared to the episodic transmission site. However, this study detected no such difference in the TLR2, TLR4, TLR9, and MAL allele frequencies between the two study sites. All polymorphisms were in Hardy Weinberg Equilibrium in the Kenyan and Papua New Guinean populations. TLR9 SNPs and length polymorphisms within the TLR2 5' untranslated region were the only mutant alleles present at a frequency greater than 10% in all populations. Conclusion Similar frequencies of TLR2, TLR4, TLR9, and MAL genetic polymorphisms in populations with different histories of malaria exposure suggest that these innate immune pathways have not been under strong selective pressure by malaria. Genotype frequencies are consistent with Hardy-Weinberg Equilibrium and the Neutral Theory, suggesting that genetic drift has influenced allele frequencies to a greater extent than selective

  19. Genetic variation in the beta 3-adrenoreceptor gene (Trp64Arg polymorphism) and its influence on anthropometric parameters and insulin resistance under a high monounsaturated versus a high polyunsaturated fat hypocaloric diet.

    Science.gov (United States)

    de Luis, D A; Aller, R; Izaola, O; Conde, R; Eiros Bouza, J M

    2013-01-01

    The aim of our study was to investigate the role of Trp64Arg polymorphism of the beta 3-adrenergic receptor (beta 3-AR) gene on metabolic changes and weight loss secondary to a high monounsaturated fat versus a high polyunsaturated fat hypocaloric diet in obese subjects. A population of 260 obese subjects was analyzed. In the basal visit, patients were randomly allocated for 3 months to either diet M (high monounsaturated fat hypocaloric diet) or diet P (high polyunsaturated fat hypocaloric diet). There were no significant differences between the positive effects (on weight, body mass index, waist circumference, fat mass) in either genotype group with both diets. With diet P and in genotype Trp64Trp, glucose levels (-6.7 ± 12.1 vs. -1.2 ± 2.2 mg/dl; p hypocaloric diets is greatest in subjects with the normal homozygous beta 3-AR gene. Improvements in total cholesterol, LDL cholesterol, triglyceride, glucose, insulin and HOMA-R levels were better than in the heterozygous group. Copyright © 2013 S. Karger AG, Basel.

  20. Single nucleotide polymorphisms in the promoter region of the IL1B gene influence outcome in multiple myeloma patients treated with high-dose chemotherapy independently of relapse treatment with thalidomide and bortezomib

    DEFF Research Database (Denmark)

    Vangsted, Annette J.; Klausen, Tobias W.; Abildgaard, Niels

    2011-01-01

    the impact on outcome of HDT, INF-α maintenance treatment, and treatment with thalidomide and bortezomib at relapse, in relation to the major identified functional polymorphisms in the promoter region of IL1B. The wild-type C-allele of IL1B C-3737T and non-carriage of the IL1B promoter haplotype TGT (−3737T...... carrying the wild-type C-allele of IL1B C-3737T (HR, 1.6 (1.1–2.4)). Furthermore, among INF-α treated patients, gene–gene interaction studies on IL1B C-3737T and NFКB1-94ins/del ATTG revealed a fourfold increase in TTF for homozygous carriers of wild-type alleles at both loci as compared to variant allele...... carriers at both loci. No relation to genotype and outcome was found for relapse patients treated with thalidomide or bortezomib. Our results indicate that a subpopulation of myeloma patients carrying the wild-type C-allele of IL1B C-3737T and non-carriers of the promoter haplotype TGT (−3737T, −1464G...

  1. Influence of insulin sensitivity and the TaqIB cholesteryl ester transfer protein gene polymorphism on plasma lecithin:cholesterol acyltransferase and lipid transfer protein activities and their response to hyperinsulinemia in non-diabetic men

    NARCIS (Netherlands)

    S.C. Riemens; A. van Tol (Arie); B.K. Stulp; R.P.F. Dullaart (Robin)

    1999-01-01

    textabstractLecithin:cholesteryl acyl transferase (LCAT), cholesteryl ester transfer protein (CETP), phospholipid transfer protein (PLTP), and lipoprotein lipases are involved in high density lipoprotein (HDL) metabolism. We evaluated the influence of insulin

  2. [CCR5, CCR2, apoe, p53, ITGB3 and HFE gene polymorphism in Western Siberia long-livers].

    Science.gov (United States)

    Ivanoshchuk, D E; Mikhaĭlova, S V; Kulikov, I V; Maksimov, V N; Voevoda, M I; Romashchenko, A G

    2012-01-01

    In order to estimate the distribution of some polymorphisms for the CCR5, CCR2, apoE, p53, ITGB3, and HFE genes in Russian long-livers from Western Siberia, a sample of 271 individuals (range 90-105 years) was examined. It was demonstrated that carriage of the delta32 polymorphism for the CCR5 gene, V64/polymorphism for the CCR2 gene, e2/e3/e4 for the apoE gene, L33P for the ITGB3 gene, as well as H63D and S65C polymorphisms for the HFE gene does not influence on predisposition to the longevity; carriage of the 282 Y allele for the HFE gene negatively influences on the longevity; carriage of the heterozygous genotype for the R72P polymorphism for the p53 gene correlates with the longevity of elderly people.

  3. Polymorphism of nickel sulfate hexahydrate

    International Nuclear Information System (INIS)

    Angel, R.J.; Finger, L.W.

    1988-01-01

    NiSO 4 .6H 2 O, M r =262.85; data collections with Mo Kα radiation, λ=0.7093 A, room temperature. Monoclinic polymorph: C2/c, a=9.880(3), b=7.228(2), c=24.130(3) A, β=98.38(2) 0 , V=1704.7(6) A 3 , Z=8, D x =2.05 g cm -3 , μ=25.54 cm -1 , F(000)=1088, R=0.031 (wR=0.038) for 2176 observed reflections. Tetragonal polymorph: P4 1 2 1 2, a=6.780 (1), c=18.285 (2) A, V=840.5 (3) A 3 , Z=4, D x =2.07 g cm -3 , μ=25.81 cm -1 , F(000)=544, R=0.045 (wR=0.050) for 2102 observed reflections. The structure of the tetragonal polymorph originally determined (without H positions) by Beevers and Lipson and refined by O'Connor and Dale and Stadnicka, Glazer and Koralewski, is confirmed by refinement of X-ray diffraction data. The structure of the monoclinic polymorph is confirmed as being isostructural with NiSO 4 .6D 2 O, and a number of other hexahydrate sulfates, e.g. MgSO 4 .6H 2 O. Both structures contain isolated [Ni(H 2 O 6 ] octahedra and [SO 4 ] tetrahedra linked by hydrogen bonding. (orig.)

  4. Gene polymorphisms in chronic periodontitis

    NARCIS (Netherlands)

    Laine, M.L.; Loos, B.G.; Crielaard, W.

    2010-01-01

    We aimed to conduct a review of the literature for gene polymorphisms associated with chronic periodontitis (CP) susceptibility. A comprehensive search of the literature in English was performed using the keywords: periodontitis, periodontal disease, combined with the words genes, mutation, or

  5. Influence of Host Interleukin-10 Polymorphisms on Development of Traveler's Diarrhea Due to Heat-Labile Enterotoxin-Producing Escherichia coli in Travelers from the United States Who Are Visiting Mexico▿

    Science.gov (United States)

    Flores, Jose; DuPont, Herbert L.; Lee, Stephanie A.; Belkind-Gerson, Jaime; Paredes, Mercedes; Mohamed, Jamal A.; Armitige, Lisa Y.; Guo, Dong-Chuan; Okhuysen, Pablo C.

    2008-01-01

    Up to 60% of U.S. visitors to Mexico develop traveler's diarrhea (TD), mostly due to enterotoxigenic Escherichia coli (ETEC) strains that produce heat-labile (LT) and/or heat-stable (ST) enterotoxins. Distinct single-nucleotide polymorphisms (SNPs) within the interleukin-10 (IL-10) promoter have been associated with high, intermediate, or low production of IL-10. We conducted a prospective study to investigate the association of SNPs in the IL-10 promoter and the occurrence of TD in ETEC LT-exposed travelers. Sera from U.S. travelers to Mexico collected on arrival and departure were studied for ETEC LT seroconversion by using cholera toxin as the antigen. Pyrosequencing was performed to genotype IL-10 SNPs. Stools from subjects who developed diarrhea were also studied for other enteropathogens. One hundred twenty-one of 569 (21.3%) travelers seroconverted to ETEC LT, and among them 75 (62%) developed diarrhea. Symptomatic seroconversion was more commonly seen in subjects who carried a genotype producing high levels of IL-10; it was seen in 83% of subjects with the GG genotype versus 54% of subjects with the AA genotype at IL-10 gene position −1082 (P, 0.02), in 71% of those with the CC genotype versus 33% of those with the TT genotype at position −819 (P, 0.005), and in 71% of those with the CC genotype versus 38% of those with the AA genotype at position −592 (P, 0.02). Travelers with the GCC haplotype were more likely to have symptomatic seroconversion than those with the ATA haplotype (71% versus 38%; P, 0.002). Travelers genetically predisposed to produce high levels of IL-10 were more likely to experience symptomatic ETEC TD. PMID:18579697

  6. Influence of host interleukin-10 polymorphisms on development of traveler's diarrhea due to heat-labile enterotoxin-producing Escherichia coli in travelers from the United States who are visiting Mexico.

    Science.gov (United States)

    Flores, Jose; DuPont, Herbert L; Lee, Stephanie A; Belkind-Gerson, Jaime; Paredes, Mercedes; Mohamed, Jamal A; Armitige, Lisa Y; Guo, Dong-Chuan; Okhuysen, Pablo C

    2008-08-01

    Up to 60% of U.S. visitors to Mexico develop traveler's diarrhea (TD), mostly due to enterotoxigenic Escherichia coli (ETEC) strains that produce heat-labile (LT) and/or heat-stable (ST) enterotoxins. Distinct single-nucleotide polymorphisms (SNPs) within the interleukin-10 (IL-10) promoter have been associated with high, intermediate, or low production of IL-10. We conducted a prospective study to investigate the association of SNPs in the IL-10 promoter and the occurrence of TD in ETEC LT-exposed travelers. Sera from U.S. travelers to Mexico collected on arrival and departure were studied for ETEC LT seroconversion by using cholera toxin as the antigen. Pyrosequencing was performed to genotype IL-10 SNPs. Stools from subjects who developed diarrhea were also studied for other enteropathogens. One hundred twenty-one of 569 (21.3%) travelers seroconverted to ETEC LT, and among them 75 (62%) developed diarrhea. Symptomatic seroconversion was more commonly seen in subjects who carried a genotype producing high levels of IL-10; it was seen in 83% of subjects with the GG genotype versus 54% of subjects with the AA genotype at IL-10 gene position -1082 (P, 0.02), in 71% of those with the CC genotype versus 33% of those with the TT genotype at position -819 (P, 0.005), and in 71% of those with the CC genotype versus 38% of those with the AA genotype at position -592 (P, 0.02). Travelers with the GCC haplotype were more likely to have symptomatic seroconversion than those with the ATA haplotype (71% versus 38%; P, 0.002). Travelers genetically predisposed to produce high levels of IL-10 were more likely to experience symptomatic ETEC TD.

  7. COMT Val 158 Met polymorphism is associated with nonverbal cognition following mild traumatic brain injury

    NARCIS (Netherlands)

    E.A. Winkler (Ethan A.); J.K. Yue (John); T.W. McAllister (Thomas W.); N.R. Temkin (Nancy); S.S. Oh (Sam S.); E.G. Burchard (Esteban); D. Hu (Donglei); A.R. Ferguson (Adam); H.F. Lingsma (Hester); J.F. Burke (John F.); M.D. Sorani (Marco); J. Rosand (Jonathan); E.L. Yuh (Esther); J. Barber (Jason); P.E. Tarapore (Phiroz E.); R.C. Gardner (Raquel C.); S. Sharma (Sourabh); G.G. Satris (Gabriela G.); C. Eng (Celeste); A.M. Puccio (Ava); K.K.W. Wang (Kevin K. W.); P. Mukherjee (Pratik); A.B. Valadka (Alex); D. Okonkwo (David); R. Diaz-Arrastia (Ramon); G. Manley (Geoffrey)

    2016-01-01

    textabstractMild traumatic brain injury (mTBI) results in variable clinical outcomes, which may be influenced by genetic variation. A single-nucleotide polymorphism in catechol-o-methyltransferase (COMT), an enzyme which degrades catecholamine neurotransmitters, may influence cognitive deficits

  8. Association between norepinephrine transporter gene (SLC6A2) polymorphisms and suicide in patients with major depressive disorder.

    Science.gov (United States)

    Kim, Yong-Ku; Hwang, Jung-A; Lee, Heon-Jeong; Yoon, Ho-Kyoung; Ko, Young-Hoon; Lee, Bun-Hee; Jung, Han-Yong; Hahn, Sang-Woo; Na, Kyoung-Sae

    2014-04-01

    Although several studies have investigated possible associations between norepinephrine neurotransmitter transporter gene (SLC6A2) polymorphisms and depression, few studies have examined associations between SLC6A2 polymorphisms and suicide. Three single-nucleotide polymorphisms (rs2242446, rs28386840, and rs5569) were measured in 550 patients: 201 with major depressive disorder (MDD) and suicide attempt/s, 160 with MDD without suicide attempts, and 189 healthy controls. Analysis of single-nucleotide polymorphisms (SNPs) and haplotype was conducted for the three groups. Subsequently, multivariate logistic regression analysis adjusting for age and gender was conducted to identify independent influences of each SNP. A possible association between suicide lethality and SLC6A2 polymorphisms was also investigated. In the genotype and allele frequency analysis, there were significant differences in rs28386840 between suicidal MDD patients and healthy controls. In the haplotype analysis, TAA (rs2242446-rs28386840-rs5569, from left to right) was associated with suicide attempts in MDD, although the significance (p=0.043) disappeared after Bonferroni correction. There were no relationships between lethality scores and SLC6A2 polymorphisms in suicidal MDD. Modest sample size and a single type of neurotransmitter analyzed (norepinephrine) are the primary limitations. Our results suggest that SLC6A2 polymorphisms were associated with suicide risk in patients with MDD. Future studies are warranted to elucidate possible mechanisms by which SLC6A2 polymorphisms influence suicide risk. Copyright © 2014 Elsevier B.V. All rights reserved.

  9. 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

  10. Personalized Medicine Digoxin Theraphy in Individuals with MDR Gene Polymorphism

    Directory of Open Access Journals (Sweden)

    Em Sutrisna

    2015-06-01

    Full Text Available Digoxin is one of digitalis drugs. Wider applicability to heart failure and arrhythmias (supraventricular requires fairly strict scrutiny because of its narrow therapeutic index. Digoxin is a substrate of P-glycoprotein (P-gp encoded by multi drugs resistance-1 (MDR1. MDR-1 gen located on chromosome 7q21.1. This gene contains 28 exons that encoded a protein of 1280 amino acids. This gene plays an important role in the absorption, distribution and elimination of many drugs. MDR1C3435T polymorphism occurs in exon 26. There are three types of MDR1C3435T gene namely MDR1C3435T CC, MDR1C3435T CT and MDR1C3435T TT. These polymorphisms will affect to the formation of P-gp and consequently to change the kinetic profile of digoxin. The change of kinetic profile causes changes in the digoxin blood levels. The method used in this review is data search based on pubmed, medline, and embase with keywords MDR and digoxin. There are several different studies of the influence of polymorphisms MDR1C3435T on blood digoxin levels. Increased levels of digoxin in the blood due to polymorphism of MDR1C3435T will be at risk of digitalis intoxication. Long-term digoxin treatment or large dose should consider the patient’s genetic profile. Distribution of polymorphism of MDR1C3435T in Javanese population is approximately TT (0,10, CT (0,52, and CC(0, 38.

  11. Circadian polymorphisms associated with affective disorders

    Directory of Open Access Journals (Sweden)

    Shekhtman Tatyana

    2009-01-01

    influence mood disorders, perhaps ultimately through regulation of MAOA and its modulation of dopamine transmission. Twenty-three associations of circadian polymorphisms with affective symptoms met nominal significance criteria (P

  12. Genetic polymorphisms in varied environments.

    Science.gov (United States)

    Powell, J R

    1971-12-03

    Thirteen experimenital populationis of Drosophila willistoni were maintained in cages, in some of which the environments were relatively constant and in others varied. After 45 weeks, the populations were assayed by gel electrophoresis for polymorphisms at 22 protein loci. The average heterozygosity per individual and the average unmber of alleles per locus were higher in populations maintained in heterogeneous environments than in populations in more constant enviroments.

  13. Polymorphism of nickel sulfate hexahydrate

    Energy Technology Data Exchange (ETDEWEB)

    Angel, R.J.; Finger, L.W.

    1988-11-15

    NiSO/sub 4/.6H/sub 2/O, M/sub r/=262.85; data collections with Mo K..cap alpha.. radiation, lambda=0.7093 A, room temperature. Monoclinic polymorph: C2/c, a=9.880(3), b=7.228(2), c=24.130(3) A, ..beta..=98.38(2)/sup 0/, V=1704.7(6) A/sup 3/, Z=8, D/sub x/=2.05 g cm/sup -3/, ..mu..=25.54 cm/sup -1/, F(000)=1088, R=0.031 (wR=0.038) for 2176 observed reflections. Tetragonal polymorph: P4/sub 1/2/sub 1/2, a=6.780 (1), c=18.285 (2) A, V=840.5 (3) A/sup 3/, Z=4, D/sub x/=2.07 g cm/sup -3/, ..mu..=25.81 cm/sup -1/, F(000)=544, R=0.045 (wR=0.050) for 2102 observed reflections. The structure of the tetragonal polymorph originally determined (without H positions) by Beevers and Lipson and refined by O'Connor and Dale and Stadnicka, Glazer and Koralewski, is confirmed by refinement of X-ray diffraction data. The structure of the monoclinic polymorph is confirmed as being isostructural with NiSO/sub 4/.6D/sub 2/O, and a number of other hexahydrate sulfates, e.g. MgSO/sub 4/.6H/sub 2/O. Both structures contain isolated (Ni(H/sub 2/O/sub 6/) octahedra and (SO/sub 4/) tetrahedra linked by hydrogen bonding.

  14. Genetic polymorphisms at the leptin receptor gene in three beef cattle breeds

    Directory of Open Access Journals (Sweden)

    Sabrina E.M. Almeida

    2008-01-01

    Full Text Available The genetic diversity of a single nucleotide polymorphism (SNP at the exon 20 (T945M of the leptin receptor gene (LEPR and of three short tandem repeats (STRs BM7225, BMS694, and BMS2145 linked to LEPR was investigated in three beef cattle herds (Brangus Ibagé, Charolais, and Aberdeen Angus. A cheap and effective new method to analyze the T945M polymorphism in cattle populations was developed and the possible role of these polymorphisms in reproduction and weight gain of postpartum cows was evaluated. High levels of genetic diversity were observed with the average heterozygosity of STRs ranging from 0.71 to 0.81. No significant association was detected between LEPR markers and reproductive parameters or daily weight gain. These negative results suggest that the LEPR gene polymorphisms, at least those herein described, do not influence postpartum cows production.

  15. Do polymorphisms in chemosensory genes matter for human ingestive behavior?

    Science.gov (United States)

    Hayes, John E; Feeney, Emma L; Allen, Alissa L

    2013-12-01

    In the last decade, basic research in chemoreceptor genetics and neurobiology have revolutionized our understanding of individual differences in chemosensation. From an evolutionary perspective, chemosensory variations appear to have arisen in response to different living environments, generally in the avoidance of toxins and to better detect vital food sources. Today, it is often assumed that these differences may drive variable food preferences and choices, with downstream effects on health and wellness. A growing body of evidence indicates chemosensory variation is far more complex than previously believed. However, just because a genetic polymorphism results in altered receptor function in cultured cells or even behavioral phenotypes in the laboratory, this variation may not be sufficient to influence food choice in free living humans. Still, there is ample evidence to indicate allelic variation in TAS2R38 predicts variation in bitterness of synthetic pharmaceuticals (e.g., propylthiouracil) and natural plant compounds (e.g., goitrin), and this variation associates with differential intake of alcohol and vegetables. Further, this is only one of 25 unique bitter taste genes ( TAS2Rs ) in humans, and emerging evidence suggests other TAS2Rs may also contain polymorphisms that a functional with respect to ingestive behavior. For example, TAS2R16 polymorphisms are linked to the bitterness of naturally occurring plant compounds and alcoholic beverage intake, a TAS2R19 polymorphism predicts differences in quinine bitterness and grapefruit bitterness and liking, and TAS2R31 polymorphisms associate with differential bitterness of plant compounds like aristolochic acid and the sulfonyl amide sweeteners saccharin and acesulfame-K. More critically with respect to food choices, these polymorphisms may vary independently from each other within and across individuals, meaning a monolithic one-size-fits-all approach to bitterness needs to be abandoned. Nor are genetic

  16. An innovative way to highlight the power of each polymorphism on elite athletes phenotype expression

    Directory of Open Access Journals (Sweden)

    Valentina Contrò

    2018-03-01

    Full Text Available The purpose of this study was to determine the probability of soccer players having the best genetic background that could increase performance, evaluating the polymorphism that are considered Performance Enhancing Polymorphism (PEPs distributed on five genes: PPARα, PPARGC1A, NRF2, ACE e CKMM. Particularly, we investigated how each polymorphism works directly or through another polymorphism to distinguish elite athletes from non-athletic population. Sixty professional soccer players (age 22.5 ± 2.2 and sixty healthy volunteers (age 21.2± 2.3 were enrolled. Samples of venous blood was used to prepare genomic DNA. The polymorphic sites were scanned using PCR-RFLP protocols with different enzyme. We used a multivariate logistic regression analysis to demonstrate an association between the five PEPs and elite phenotype. We found statistical significance in NRF2 (AG/GG genotype polymorphism/soccer players association (p<0.05 as well as a stronger association in ACE polymorphism (p=0.02. Particularly, we noticed that the ACE ID genotype and even more the II genotype are associated with soccer player phenotype. Although the other PEPs had no statistical significance, we proved that some of these may work indirectly, amplifying the effect of another polymorphism; for example, seems that PPARα could acts on NRF2 (GG enhancing the effect of the latter, notwithstanding it had not shown a statistical significance. In conclusion, to establish if a polymorphism can influence the performance, it is necessary to understand how they act and interact, directly and indirectly, on each other

  17. Polymorphism of human haptoglobin and its clinical importance

    Directory of Open Access Journals (Sweden)

    Vânia Peretti de Albuquerque Wobeto

    2008-01-01

    Full Text Available Haptoglobin (Hp is a plasma glycoprotein, the main biological function of which is to bind free hemoglobin (Hb and prevent the loss of iron and subsequent kidney damage following intravascular hemolysis. Haptoglobin is also a positive acute-phase protein with immunomodulatory properties. In humans, the HP locus is polymorphic, with two codominant alleles (HP1 and HP2 that yield three distinct genotypes/phenotypes (Hp1-1, Hp2-1 and Hp2-2. The corresponding proteins have structural and functional differences that may influence the susceptibility and/or outcome in several diseases. This article summarizes the available data on the structure and functions of Hp and the possible effects of Hp polymorphism in a number of important human disorders.

  18. Genotyping of presenilin-1 polymorphism in amyotrophic lateral sclerosis.

    Science.gov (United States)

    Panas, M; Karadima, G; Kalfakis, N; Psarrou, O; Floroskoufi, P; Kladi, A; Petersen, M B; Vassilopoulos, D

    2000-12-01

    The mechanisms underlying motor neuron degeneration in amyotrophic lateral sclerosis are not fully understood. Recent studies suggest that apoptosis is involved in the abnormal neural death that occurs in this devastating disease. Presenilin-1, a transmembrane protein, seems to be implicated in apoptosis. To determine whether presenilin-1 intron 8 polymorphism has an influence in the course of amyotrophic lateral sclerosis, we examined this polymorphism genotypes in a large group of patients (n = 72) with amyotrophic lateral sclerosis and in a random sample of 213 healthy individuals. The results showed a significant difference in genotype (P < 0.04) and allele (P < 0.03) distribution between patients controls. These results suggest a possible intervention of presenilin-1 in the pathogenesis of amyotrophic lateral sclerosis.

  19. Cyclooxygenase-2 polymorphisms in Parkinson's disease.

    Science.gov (United States)

    Håkansson, Anna; Bergman, Olle; Chrapkowska, Cecilia; Westberg, Lars; Belin, Andrea Carmine; Sydow, Olof; Johnels, Bo; Olson, Lars; Holmberg, Björn; Nissbrandt, Hans

    2007-04-05

    Accumulating evidence indicate that cyclooxygenase-2 (COX-2) is of pathophysiological importance for the neurodegeneration in Parkinson's disease (PD). For example, in a large epidemiological study, use of NSAIDs was associated with a lower risk of PD. Genetic variants of the COX-2 gene might therefore influence the risk of developing the disease. The genotype distribution of four common single nucleotide polymorphisms (SNPs) in the COX-2 gene (rs689466:A496G, rs20417:G926C, rs5277:G3050C, rs5275:C8473T) was analyzed in PD patients and control subjects in a Swedish population. No differences could be seen between the PD-patient and controls regarding the A496G, G926C, and G3050C SNPs, but the allele frequency of the C8473T SNP was found to differ when male patients were compared to controls (P = 0.007). In females no difference could be seen between PD-patients and controls. In conclusion, the results suggest a possible influence of the COX-2 C8473T SNP in PD, although it only seems to be of importance in men. (c) 2006 Wiley-Liss, Inc.

  20. Aspects and Polymorphism in AspectJ

    DEFF Research Database (Denmark)

    Lorenz, David Harel; Ernst, Erik

    2003-01-01

    There are two important points of view on inclusion or subtype polymorphism in object-oriented programs, namely polymorphic access and dynamic dispatch. These features are essential for object-oriented programming, and it is worthwhile to consider whether they are supported in aspect-oriented......J as the basis for the presentation. The results are not exclusive to AspectJ---aspectual polymorphism may make aspects in any comparable AOSD language more expressive and reusable across programs, while preserving safety....

  1. Lack of Association between Interleukin-18 –607 C/A Gene Polymorphism and Pulmonary Tuberculosis in Zahedan, Southeast Iran

    Directory of Open Access Journals (Sweden)

    M. Taheri

    2012-01-01

    Full Text Available Interleukin-18 (IL-18 plays a critical role in immune response, contributing to the pathogenesis and pathophysiology of infectious diseases. Polymorphisms in the IL-18 genes are known to influence expression levels and may be associated with outcome of infections. The objective of this study was to determine whether the presence of IL-18 polymorphisms –607 A/C (rs1946518 was associated with tuberculosis disease. We investigated the functional polymorphism of IL-18 (rs1946518 in 174 patients with pulmonary tuberculosis (PTB and 177 healthy subjects. Genotype analysis was done using tetra amplification refractory mutation system-PCR (T-ARMS-PCR. The allelic and genotypic frequencies of the IL-18 polymorphism did not differ significantly between PTB and the controls. Our finding suggests that IL-18 polymorphism (rs1946518 may not be a risk factor for susceptibility to tuberculosis in a sample of Iranian population. Further studies are required to validate our findings.

  2. Genetic polymorphisms of Interleukin-18 are not associated with allograft function in kidney transplant recipients

    Directory of Open Access Journals (Sweden)

    Wenna Gleyce Araújo do Nascimento

    2014-06-01

    Full Text Available Interleukin 18 (IL-18 is a proinflammatory cytokine that plays a role in host defense by upregulating both innate and acquired immune responses. Analysis of IL 18 polymorphisms may be clinically important since their roles have been recognized in a variety of inflammatory and autoimmune disorders. However, the role of this cytokine polymorphisms in kidney transplant still remains unclear. In this study, we evaluated the associations between IL 18 polymorphisms and graft function assessed by creatinine clearance in kidney transplant recipients. A total of 82 kidney transplant recipients and 183 healthy controls were enrolled, and frequencies of alleles, genotypes and haplotypes for IL 18 polymorphisms were determined and compared with creatinine clearance. The -607C/A (rs1946518 and -137C/G (rs187238 variant alleles in the 18 gene were determined by polymerase chain reaction. In our study, no significant association was found between the IL 18 variants and creatinine clearance (p > 0.05. Nonetheless, polymorphism analysis revealed an increase in the frequency of the IL18 major haplotype -607C/-137G in kidney transplant patients (odds ratio 2.57, 95% confidence interval 1.45-4.55, p = 0.0014. Finally, we found that IL 18 polymorphisms did not influence the renal function and that IL18 haplotype -607C/-137G seems to be associated with kidney transplant recipients.

  3. Genetic polymorphisms of Interleukin-18 are not associated with allograft function in kidney transplant recipients.

    Science.gov (United States)

    do Nascimento, Wenna Gleyce Araújo; Cilião, Daiani Alves; Genre, Julieta; Gondim, Dikson Dibe; Alves, Renata Gomes; Hassan, Neife Deghaide; Lima, Francisco Pignataro; Pereira, Maurício Galvão; Donadi, Eduardo Antônio; de Oliveira Crispim, Janaina Cristiana

    2014-06-01

    Interleukin 18 (IL-18) is a proinflammatory cytokine that plays a role in host defense by upregulating both innate and acquired immune responses. Analysis of IL18 polymorphisms may be clinically important since their roles have been recognized in a variety of inflammatory and autoimmune disorders. However, the role of this cytokine polymorphisms in kidney transplant still remains unclear. In this study, we evaluated the associations between IL18 polymorphisms and graft function assessed by creatinine clearance in kidney transplant recipients. A total of 82 kidney transplant recipients and 183 healthy controls were enrolled, and frequencies of alleles, genotypes and haplotypes for IL18 polymorphisms were determined and compared with creatinine clearance. The -607C/A (rs1946518) and -137C/G (rs187238) variant alleles in the IL18 gene were determined by polymerase chain reaction. In our study, no significant association was found between the IL18 variants and creatinine clearance (p > 0.05). Nonetheless, polymorphism analysis revealed an increase in the frequency of the IL18 major haplotype -607C/-137G in kidney transplant patients (odds ratio 2.57, 95% confidence interval 1.45-4.55, p = 0.0014). Finally, we found that IL18 polymorphisms did not influence the renal function and that IL18 haplotype -607C/-137G seems to be associated with kidney transplant recipients.

  4. Comparison of macro and micro Raman measurement for reliable quantitative analysis of pharmaceutical polymorphs.

    Science.gov (United States)

    Paiva, Eduardo M; da Silva, Vitor H; Poppi, Ronei J; Pereira, Claudete F; Rohwedder, Jarbas J R

    2018-05-12

    This work reports on the use of micro- and macro-Raman measurements for quantification of mebendazole (MBZ) polymorphs A, B, and C in mixtures. Three Raman spectrophotometers were studied with a laser spot size of 3, 80 and 100 μm and spectral resolutions of 3.9, 9 and 4 cm -1 , respectively. The samples studied were ternary mixtures varying the MBZ polymorphs A and C from 0 to 100% and polymorph B from 0 to 30%. Partial Least Squares (PLS) regression models were developed using the pre-processing spectra (2nd derivative) of the ternary mixtures. The best performance was obtained when the macro-Raman configuration was applied, obtaining RMSEP values of 1.68%, 1.24% and 2.03% w/w for polymorphs A, B, and C, respectively. In general, micro-Raman presented worst results for MBZ polymorphs prediction because the spectra obtained with this configuration does not represent the bulk proportion of mixtures, which have different particle morphologies and sizes. In addition, the influence of these particle features on micro-Raman measurements was also studied. Finally, the results demonstrated that reliable analytical quantifying of MBZ polymorphs can be reached using a laser with wider area illuminated, thus enabling acquisition of more reproductive and representative spectra of the mixtures. Copyright © 2018 Elsevier B.V. All rights reserved.

  5. Effects of polymorphisms in ovine and caprine prion protein alleles on cell-free conversion

    Directory of Open Access Journals (Sweden)

    Eiden Martin

    2011-02-01

    Full Text Available Abstract In sheep polymorphisms of the prion gene (PRNP at the codons 136, 154 and 171 strongly influence the susceptibility to scrapie and bovine spongiform encephalopathy (BSE infections. In goats a number of other gene polymorphisms were found which are suspected to trigger similar effects. However, no strong correlation between polymorphisms and TSE susceptibility in goats has yet been obtained from epidemiological studies and only a low number of experimental challenge data are available at present. We have therefore studied the potential impact of these polymorphisms in vitro by cell-free conversion assays using mouse scrapie strain Me7. Mouse scrapie brain derived PrPSc served as seeds and eleven recombinant single mutation variants of sheep and goat PrPC as conversion targets. With this approach it was possible to assign reduced conversion efficiencies to specific polymorphisms, which are associated to low frequency in scrapie-affected goats or found only in healthy animals. Moreover, we could demonstrate a dominant-negative inhibition of prion polymorphisms associated with high susceptibility by alleles linked to low susceptibility in vitro.

  6. Xmni polymorphism and disease severity in patients with beta thalassemia from northern Pakistan

    International Nuclear Information System (INIS)

    Hanif, T.B.; Ahmed, S.; Anwar, J.

    2015-01-01

    Thalassemia is a heterogeneous disorder and several genetic factors influence the severity of thalassemia. An accurate and early diagnosis of a mild thalassemia genotype helps to avoid unnecessary transfusion and its complications. The aim of this study is to identify the association between XmnI polymorphism and disease severity in patients with ?-thalassemia from northern Pakistan. Methods: The cross sectional study was conducted at the Department of Haematology, Armed Forces Institute of Pathology (AFIP) Rawalpindi, from September 2006 to June 2009. A total of 90 subjects including 30 with thalassemia major, 30 with thalassemia intermedia and 30 normal individuals were studied. DNA from each subject was tested for 15 ?-thalassemia mutations and the presence of XmnI polymorphism using Amplification Refractory Mutation System and Restriction Fragment Length Polymorphism respectively. Results: One normal and one thalassemia major subject were found to be positive for homozygous and heterozygous XmnI polymorphism respectively. Among the thalassemia intermedia group, XmnI polymorphism was found in 12/30 patients, of whom 10 were homozygous and 2 were heterozygous for it. Conclusion: XmnI polymorphism is an important genotypic factor in Pakistani population for making a prospective diagnosis of thalassemia intermedia and predicting the severity of the disease. (author)

  7. The influence of iron status and genetic polymorphisms in the HFE gene on the risk for postoperative complications after bariatric surgery: a prospective cohort study in 1,064 patients

    Directory of Open Access Journals (Sweden)

    Freedman-Weiss Mollie

    2011-01-01

    Full Text Available Abstract Background Gastric bypass surgery is a highly effective therapy for long-term weight loss in severely obese patients, but carries significant perioperative risks including infection, wound dehiscence, and leaks from staple breakdown. Iron status can affect immune function and wound healing, thus may influence peri-operative complications. Common mutations in the HFE gene, the gene responsible for the iron overload disorder hereditary hemochromatosis, may impact iron status. Methods We analyzed 1064 extremely obese Caucasian individuals who underwent open and laparoscopic Roux-n-Y gastric bypass surgery at the Geisinger Clinic. Serum iron, ferritin, transferrin, and iron binding capacity were measured pre-operatively. All patients had intra-operative liver biopsies and were genotyped for the C282Y and H63D mutations in the HFE gene. Associations between surgical complications and serum iron measures, HFE gene status, and liver iron histology were determined. Results We found that increased serum iron and transferrin saturation were present in patients with any post-operative complication, and that increased serum ferritin was also increased in patients with major complications. Increased serum transferrin saturation was also associated with wound complications in open RYGB, and transferrin saturation and ferritin with prolonged lengths of stay. The presence of 2 or more HFE mutations was associated with overall complications as well as wound complications in open RYGB. No differences were found in complication rates between those with stainable liver iron and those without. Conclusion Serum iron status and HFE genotype may be associated with complications following RYGB surgery in the extremely obese.

  8. Influence of IL28B polymorphisms on response to a lower-than-standard dose peg-IFN-α 2a for genotype 3 chronic hepatitis C in HIV-coinfected patients.

    Directory of Open Access Journals (Sweden)

    Luis F López-Cortés

    Full Text Available Data on which to base definitive recommendations on the doses and duration of therapy for genotype 3 HCV/HIV-coinfected patients are scarce. We evaluated the efficacy of a lower peginterferon-α 2a dose and a shorter duration of therapy than the current standard of care in genotype 3 HCV/HIV-coinfected patients.Pilot, open-label, single arm clinical trial which involved 58 Caucasian HCV/HIV-coinfected patients who received weekly 135 µg peginterferon-α 2a plus ribavirin 400 mg twice daily during 20 weeks after attaining undetectable viremia. The relationships between baseline patient-related variables, including IL28B genotype, plasma HCV-RNA, ribavirin dose/kg, peginterferon-α 2a and ribavirin levels with virological responses were analyzed. Only 4 patients showed lack of response and 5 patients dropped out due to adverse events related to the study medication. Overall, sustained virologic response (SVR rates were 58.3% by intention-to-treat and 71.4% by per protocol analysis, respectively. Among patients with rapid virologic response (RVR, SVR and relapses rates were 92.6% and 7.4%, respectively. No relationships were observed between viral responses and ribavirin dose/kg, peginterferon-α 2a concentrations, ribavirin levels or rs129679860 genotype.Weekly 135 µg pegIFN-α 2a could be as effective as the standard 180 µg dose, with a very low incidence of severe adverse events. A 24-week treatment duration appears to be appropriate in patients achieving RVR, but extending treatment up to just 20 weeks beyond negativization of viremia is associated with a high relapse rate in those patients not achieving RVR. There was no influence of IL28B genotype on the virological responses.ClinicalTrials.gov NCT00553930.

  9. gene polymorphism and its serum lev

    Indian Academy of Sciences (India)

    Navya

    polymorphisms and its serum level with the risk of MetS as well as their ... population for quantifying insulin resistance and β-cell function (Matthews et al. 1985). .... of IL-10 -819 C >T gene polymorphism (Co-dominant model) was significantly.

  10. using random amplified polymorphic DNA (RAPD)

    African Journals Online (AJOL)

    To study the pattern of genetic diversity in 45 genotypes of common bean, 19 RAPD primers were used. Of 253 bands produced, 236 bands (94.22%) were polymorphic in which maximum number (20 polymorphic bands) were observed in the profiles of the primer OPB-07. Highest PIC value (0.79) was observed for the ...

  11. Methylenetetrahydrofolate reductase gene polymorphism in type 1 ...

    African Journals Online (AJOL)

    In patients with type-I diabetes mellitus folate deficiency is associated with endothelial dysfunction. So, polymorphism in genes involved in folate metabolism may have a role in vascular disease. This study was designed to evaluate the relationship between methylenetetrahydrofolate reductase (MTHFR) gene polymorphism ...

  12. Glutathione enzyme and selenoprotein polymorphisms associate with mercury biomarker levels in Michigan dental professionals

    Energy Technology Data Exchange (ETDEWEB)

    Goodrich, Jaclyn M.; Wang, Yi [Department of Environmental Health Sciences, University of Michigan School of Public Health, 1415 Washington Heights, Ann Arbor, MI 48109 (United States); Gillespie, Brenda [Department of Biostatistics, University of Michigan School of Public Health, 1415 Washington Heights, Ann Arbor, MI 48109 (United States); Werner, Robert [Department of Environmental Health Sciences, University of Michigan School of Public Health, 1415 Washington Heights, Ann Arbor, MI 48109 (United States); Department of Physical Medicine and Rehabilitation, University of Michigan, 325 E. Eisenhower Parkway Suite 100, Ann Arbor, MI 48108 (United States); Franzblau, Alfred [Department of Environmental Health Sciences, University of Michigan School of Public Health, 1415 Washington Heights, Ann Arbor, MI 48109 (United States); Basu, Niladri, E-mail: niladri@umich.edu [Department of Environmental Health Sciences, University of Michigan School of Public Health, 1415 Washington Heights, Ann Arbor, MI 48109 (United States)

    2011-12-15

    Mercury is a potent toxicant of concern to both the general public and occupationally exposed workers (e.g., dentists). Recent studies suggest that several genes mediating the toxicokinetics of mercury are polymorphic in humans and may influence inter-individual variability in mercury accumulation. This work hypothesizes that polymorphisms in key glutathione synthesizing enzyme, glutathione s-transferase, and selenoprotein genes underlie inter-individual differences in mercury body burden as assessed by analytical mercury measurement in urine and hair, biomarkers of elemental mercury and methylmercury, respectively. Urine and hair samples were collected from a population of dental professionals (n = 515), and total mercury content was measured. Average urine (1.06 {+-} 1.24 ug/L) and hair mercury levels (0.49 {+-} 0.63 ug/g) were similar to national U.S. population averages. Taqman assays were used to genotype DNA from buccal swab samples at 15 polymorphic sites in genes implicated in mercury metabolism. Linear regression modeling assessed the ability of polymorphisms to modify the relationship between mercury biomarker levels and exposure sources (e.g., amalgams, fish consumption). Five polymorphisms were significantly associated with urine mercury levels (GSTT1 deletion), hair mercury levels (GSTP1-105, GSTP1-114, GSS 5 Prime ), or both (SEPP1 3 Prime UTR). Overall, this study suggests that polymorphisms in selenoproteins and glutathione-related genes may influence elimination of mercury in the urine and hair or mercury retention following exposures to elemental mercury (via dental amalgams) and methylmercury (via fish consumption). -- Highlights: Black-Right-Pointing-Pointer We explore the influence of 15 polymorphisms on urine and hair Hg levels. Black-Right-Pointing-Pointer Urine and hair Hg levels in dental professionals were similar to the US population. Black-Right-Pointing-Pointer GSTT1 and SEPP1 polymorphisms associated with urine Hg levels. Black

  13. Glutathione enzyme and selenoprotein polymorphisms associate with mercury biomarker levels in Michigan dental professionals

    International Nuclear Information System (INIS)

    Goodrich, Jaclyn M.; Wang, Yi; Gillespie, Brenda; Werner, Robert; Franzblau, Alfred; Basu, Niladri

    2011-01-01

    Mercury is a potent toxicant of concern to both the general public and occupationally exposed workers (e.g., dentists). Recent studies suggest that several genes mediating the toxicokinetics of mercury are polymorphic in humans and may influence inter-individual variability in mercury accumulation. This work hypothesizes that polymorphisms in key glutathione synthesizing enzyme, glutathione s-transferase, and selenoprotein genes underlie inter-individual differences in mercury body burden as assessed by analytical mercury measurement in urine and hair, biomarkers of elemental mercury and methylmercury, respectively. Urine and hair samples were collected from a population of dental professionals (n = 515), and total mercury content was measured. Average urine (1.06 ± 1.24 ug/L) and hair mercury levels (0.49 ± 0.63 ug/g) were similar to national U.S. population averages. Taqman assays were used to genotype DNA from buccal swab samples at 15 polymorphic sites in genes implicated in mercury metabolism. Linear regression modeling assessed the ability of polymorphisms to modify the relationship between mercury biomarker levels and exposure sources (e.g., amalgams, fish consumption). Five polymorphisms were significantly associated with urine mercury levels (GSTT1 deletion), hair mercury levels (GSTP1-105, GSTP1-114, GSS 5′), or both (SEPP1 3′UTR). Overall, this study suggests that polymorphisms in selenoproteins and glutathione-related genes may influence elimination of mercury in the urine and hair or mercury retention following exposures to elemental mercury (via dental amalgams) and methylmercury (via fish consumption). -- Highlights: ► We explore the influence of 15 polymorphisms on urine and hair Hg levels. ► Urine and hair Hg levels in dental professionals were similar to the US population. ► GSTT1 and SEPP1 polymorphisms associated with urine Hg levels. ► Accumulation of Hg in hair following exposure from fish was modified by genotype. ► GSTP1, GSS

  14. Lack of association between PCK1 polymorphisms and obesity, physical activity, and fitness in European Youth Heart Study (EYHS)

    DEFF Research Database (Denmark)

    Vimaleswaran, Karani S; Franks, Paul W; Brage, Soren

    2010-01-01

    genetic variation in the PCK1 gene influences obesity-related traits, PA, and fitness, and to examine whether PA and fitness attenuate the influence of the PCK1 polymorphisms on obesity in children. Analyses were undertaken on data from Danish and Estonian children (958 boys and 1,104 girls) from...... the European Youth Heart Study (EYHS), a school-based, cross-sectional study of children (mean ± s.d. age: 9.6 ± 0.4 years) and adolescents (15.5 ± 0.5 years). We genotyped eight polymorphisms that captured the common genetic variations in the PCK1 gene. The association between the PCK1 polymorphisms and BMI......, waist circumference (WC), sum of four skinfolds, PA, and fitness was tested using an additive model adjusted for age, age-group, gender, maturity, and country. Interactions were tested by including interaction terms in the model. None of the polymorphisms were significantly associated with BMI, WC, sum...

  15. Polymorphism

    Indian Academy of Sciences (India)

    crumbled to dirty grey and the soldiers believed that it is the wrath of God; their .... more molecules of water leave the beaker progressively concentrating the solution ..... spectrum antibacterial fluoroquinolone for the treatment of prostate and ...

  16. Twinning of cubic diamond explains reported nanodiamond polymorphs

    Science.gov (United States)

    Németh, Péter; Garvie, Laurence A. J.; Buseck, Peter R.

    2015-12-01

    The unusual physical properties and formation conditions attributed to h-, i-, m-, and n-nanodiamond polymorphs has resulted in their receiving much attention in the materials and planetary science literature. Their identification is based on diffraction features that are absent in ordinary cubic (c-) diamond (space group: Fd-3m). We show, using ultra-high-resolution transmission electron microscope (HRTEM) images of natural and synthetic nanodiamonds, that the diffraction features attributed to the reported polymorphs are consistent with c-diamond containing abundant defects. Combinations of {113} reflection and rotation twins produce HRTEM images and d-spacings that match those attributed to h-, i-, and m-diamond. The diagnostic features of n-diamond in TEM images can arise from thickness effects of c-diamonds. Our data and interpretations strongly suggest that the reported nanodiamond polymorphs are in fact twinned c-diamond. We also report a new type of twin ( rotational), which can give rise to grains with dodecagonal symmetry. Our results show that twins are widespread in diamond nanocrystals. A high density of twins could strongly influence their applications.

  17. Paraoxonase1 Genetic Polymorphisms in a Mixed Ancestry African Population

    Directory of Open Access Journals (Sweden)

    M. Macharia

    2014-01-01

    Full Text Available Paraoxonase 1 (PON1 activity is markedly influenced by coding polymorphisms, Q/R at position 192 and M/L at position 55 of the PON1 gene. We investigated the frequencies of these polymorphisms and their effects on PON1 and antioxidant activities in 844 South African mixed ancestry individuals. Genotyping was done using allele-specific TaqMan technology, PON1 activities were measured using paraoxon and phenylacetate, oxidative status was determined by measuring the antioxidant activities of ferric reducing antioxidant power and trolox equivalent antioxidant capacity, and lipid peroxidation markers included malondialdehyde and oxidized LDL. The frequencies of Q192R and L55M were 47.6% and 28.8%, respectively, and the most common corresponding alleles were 192R (60.4% and 55M (82.6%. The Q192 was significantly associated with 5.8 units’ increase in PON1 concentration and 15.4 units’ decrease in PONase activity after adjustment for age, sex, BMI, and diabetes, with suggestion of differential effects by diabetes status. The PON1 L55 variant was associated with none of the measured indices. In conclusion, we have shown that the Q192R polymorphism is a determinant of both PON1 concentration and activity and this association appeared to be enhanced in subjects with diabetes.

  18. Twinning of cubic diamond explains reported nanodiamond polymorphs.

    Science.gov (United States)

    Németh, Péter; Garvie, Laurence A J; Buseck, Peter R

    2015-12-16

    The unusual physical properties and formation conditions attributed to h-, i-, m-, and n-nanodiamond polymorphs has resulted in their receiving much attention in the materials and planetary science literature. Their identification is based on diffraction features that are absent in ordinary cubic (c-) diamond (space group: Fd-3m). We show, using ultra-high-resolution transmission electron microscope (HRTEM) images of natural and synthetic nanodiamonds, that the diffraction features attributed to the reported polymorphs are consistent with c-diamond containing abundant defects. Combinations of {113} reflection and rotation twins produce HRTEM images and d-spacings that match those attributed to h-, i-, and m-diamond. The diagnostic features of n-diamond in TEM images can arise from thickness effects of c-diamonds. Our data and interpretations strongly suggest that the reported nanodiamond polymorphs are in fact twinned c-diamond. We also report a new type of twin ( rotational), which can give rise to grains with dodecagonal symmetry. Our results show that twins are widespread in diamond nanocrystals. A high density of twins could strongly influence their applications.

  19. Genetic polymorphism in postoperative sepsis after open heart surgery in infants.

    Science.gov (United States)

    Fakhri, Dicky; Djauzi, Samsuridjal; Murni, Tri Wahyu; Rachmat, Jusuf; Harahap, Alida Roswita; Rahayuningsih, Sri Endah; Mansyur, Muchtaruddin; Santoso, Anwar

    2016-05-01

    Sepsis is one of the complications following open heart surgery. Toll-like receptor 2 and toll-interacting protein polymorphism influence the immune response after open heart surgery. This study aimed to assess the genetic distribution of toll-like receptor 2 N199N and toll-interacting protein rs5743867 polymorphism in the development of postoperative sepsis. A prospective cohort study was conducted in 108 children open heart surgery with a Basic Aristotle score ≥6. Patients with an accompanying congenital anomaly, human immunodeficiency virus infection, or history of previous open heart surgery were excluded. The patients' nutritional status and genetic polymorphism were assessed prior to surgery. The results of genetic polymorphism were obtained through genotyping. Patients' ages on the day of surgery and cardiopulmonary bypass times were recorded. The diagnosis of sepsis was established according to Surviving Sepsis Campaign criteria. Postoperative sepsis was observed in 21% of patients. There were 92.6% patients with toll-like receptor 2 N199N polymorphism and 52.8% with toll-interacting protein rs5743867 polymorphism. Toll-like receptor 2 N199N polymorphism tends to increase the risk of sepsis (odds ratio = 1.974; 95% confidence interval: 0.23-16.92; p = 0.504), while toll-interacting protein rs5743867 polymorphism tends to decrease the risk of sepsis (odds ratio = 0.496; 95% confidence interval: 0.19-1.27; p = 0.139) in infants open heart surgery. © The Author(s) 2016.

  20. CYTOKINES GENETIC POLYMORPHISM: THE PAST AND THE FUTURE

    Directory of Open Access Journals (Sweden)

    L. V. Puzyryova

    2016-01-01

    Full Text Available The molecular genetics opens the new horizons in modern medicine, especially now when many diseases are given huge value in a type of their prevalence among various groups of population. Extremely high interleukin genes polymorphism degrees are studied well especially genetic polymorphism of tumor necrosis factor. Patients with HIV infection in the territory of Russia cause now the highest degree of mortality that is the most actual and socially significant problem of healthcare. This problems studying attracts many researchers. Works in respect of genetic immunity to a virus and influence of cytokines production on the disease forecast are especially interesting. One of the HIV replication influencing factors are cytokines, some of which, including the tumor necrosis factor and interleukin-6 can promote replication of HIV, raising an expression of virus regulatory genes. During disease progress in parallel of anti-inflammatory cytokines level increase (causing in this case rather ineffective antibodies level increase there is an T-helpers suppression stimulating a strong cellular component. Cytokine network functioning during HIV infection depends on many reasons which the individual variation in cytokine production caused by a number of genetic features, as well as an existence of opportunistic infection. Cytokines polymorphism determination in HIV infected patients is necessary in clinical practice for disease progression forecast to adverse fast transition to AIDS that it is important to consider in a choice of tactics of the supporting therapy of HIV-positive patients. Considering insufficient efficiency of modern methods of treatment, restoration and modulation of cytokines balance will increase anti-virus activity of immune system, influencing the factors blocking replication of a HIV.

  1. Insertional Polymorphisms of Endogenous Feline Leukemia Viruses

    Science.gov (United States)

    Roca, Alfred L.; Nash, William G.; Menninger, Joan C.; Murphy, William J.; O'Brien, Stephen J.

    2005-01-01

    The number, chromosomal distribution, and insertional polymorphisms of endogenous feline leukemia viruses (enFeLVs) were determined in four domestic cats (Burmese, Egyptian Mau, Persian, and nonbreed) using fluorescent in situ hybridization and radiation hybrid mapping. Twenty-nine distinct enFeLV loci were detected across 12 of the 18 autosomes. Each cat carried enFeLV at only 9 to 16 of the loci, and many loci were heterozygous for presence of the provirus. Thus, an average of 19 autosomal copies of enFeLV were present per cat diploid genome. Only five of the autosomal enFeLV sites were present in all four cats, and at only one autosomal locus, B4q15, was enFeLV present in both homologues of all four cats. A single enFeLV occurred in the X chromosome of the Burmese cat, while three to five enFeLV proviruses occurred in each Y chromosome. The X chromosome and nine autosomal enFeLV loci were telomeric, suggesting that ectopic recombination between nonhomologous subtelomeres may contribute to enFeLV distribution. Since endogenous FeLVs may affect the infectiousness or pathogenicity of exogenous FeLVs, genomic variation in enFeLVs represents a candidate for genetic influences on FeLV leukemogenesis in cats. PMID:15767400

  2. Apolipoprotein E Gene Polymorphism and Its Association with Cardiovascular Heart Disease Risk Factors in Type 2 Diabetes Mellitus

    OpenAIRE

    Amani Ashari; Julia Omar; Arif Hashim; Shahrul Hamid

    2016-01-01

    Apolipoprotein E (APOE) gene polymorphism has influence on serum lipids which relates to cardiovascular risk. The purpose of this study was to determine the frequency distribution of APOE alleles among Malaysian Type 2 Diabetes Mellitus (DM) patients with and without coronary artery disease (CAD) and their association with serum lipid profiles. A total of 115 patients were recruited in which 78 patients had Type 2 DM without CAD and 37 patients had Type 2 DM with CAD. The APOE polymorphism wa...

  3. Role of inflammation gene polymorphisms on pain and response to radiotherapy in multiple myeloma patients with painful bone destructions

    OpenAIRE

    Rudžianskienė, Milda; Inčiūra, Arturas; Gerbutavičius, Rolandas; Dambrauskienė, Rūta; Rudžianskas, Viktoras; Juozaitytė, Elona

    2016-01-01

    Background: Previous researches have demonstrated, that the severity of pain perception and it’s response to analgesia is highly dependent on gene polymorphism encoding for cytokines. We evaluated 12 single nucleotide polymorphisms (SNP) in 6 genes encoding for cytokines in multiple myeloma patients (n = 81) and assessed their influence on pain severity and response to palliative radiotherapy. Methods: Pain intensity was assessed by Visual Analogue Scale. The total dose of opioids was convert...

  4. Interleukin 17 Receptor Gene Polymorphism in Periimplantitis and Chronic Periodontitis

    Directory of Open Access Journals (Sweden)

    Mahdi Kadkhodazadeh

    2013-05-01

    Full Text Available Gene polymorphism of cytokines influencing their function has been known as a contributing factor in the pathogenesis of inflammatory diseases of the tooth and implant supporting tissues. The aim of this study was to investigate the association of IL-17R gene polymorphism (rs879576 with chronic periodontitis and periimplantitis in an Iranian population. 73 patients with chronic periodontitis, 37 patients with periimplantitis and 83 periodontally healthy patients were enrolled in this study. 5cc blood was obtained from each subject’s arm vein and transferred to tubes containing EDTA. Genomic DNA was extracted using Miller's Salting Out technique. The DNA was transferred into 96 division plates, transported to Kbioscience Institute in United Kingdom and analyzed using the Kbioscience Competitive Allele Specific PCR (KASP technique. Chi-square and Kruskal Wallis tests were used to analyze differences in the expression of genotypes and frequency of alleles in disease and control groups (P-Value less than 0.05 was considered statistically significant. There were no significant differences between periodontitis, periimplantitis with AA, GG, GA genotype of IL-17R gene (P=0.8239. Also comparison of frequency of alleles in SNP rs879576 of IL-17R gene between the chronic periodontitis group and periimplantitis group did not revealed statistically significant differences (P=0.8239. The enigma of IL-17 and its polymorphism-role in periodontitis and periimplantitis is yet to be investigated more carefully throughout further research but this article demonstrates that polymorphism of IL-17R plays no significant role in incidence of chronic periodontitis and Periimplantitis.

  5. Interleukin 17 receptor gene polymorphism in periimplantitis and chronic periodontitis.

    Directory of Open Access Journals (Sweden)

    Mahdi Kadkhodazadeh

    2013-06-01

    Full Text Available Gene polymorphism of cytokines influencing their function has been known as a contributing factor in the pathogenesis of inflammatory diseases of the tooth and implant supporting tissues. The aim of this study was to investigate the association of IL-17R gene polymorphism (rs879576 with chronic periodontitis and periimplantitis in an Iranian population. 73 patients with chronic periodontitis, 37 patients with periimplantitis and 83 periodontally healthy patients were enrolled in this study. 5cc blood was obtained from each subject's arm vein and transferred to tubes containing EDTA. Genomic DNA was extracted using Miller's Salting Out technique. The DNA was transferred into 96 division plates, transported to Kbioscience Institute in United Kingdom and analyzed using the Kbioscience Competitive Allele Specific PCR (KASP technique. Chi-square and Kruskal Wallis tests were used to analyze differences in the expression of genotypes and frequency of alleles in disease and control groups (P-Value less than 0.05 was considered statistically significant. There were no significant differences between periodontitis, periimplantitis with AA, GG, GA genotype of IL-17R gene (P=0.8239. Also comparison of frequency of alleles in SNP rs879576 of IL-17R gene between the chronic periodontitis group and periimplantitis group did not revealed statistically significant differences (P=0.8239. The enigma of IL-17 and its polymorphism-role in periodontitis and periimplantitis is yet to be investigated more carefully throughout further research but this article demonstrates that polymorphism of IL-17R plays no significant role in incidence of chronic periodontitis and Periimplantitis.

  6. Association between IL-1β polymorphisms and gastritis risk

    Science.gov (United States)

    Sun, Xiaoming; Cai, Hongxing; Li, Zhouru; Li, Shanshan; Yin, Wenjiang; Dong, Guokai; Kuai, Jinxia; He, Yihui; Jia, Jing

    2017-01-01

    Abstract Background: Helicobacter pylori (H. pylori) infection of the human stomach regularly leads to chronic gastric inflammation. The cytokine gene interleukin (IL)-1β has been implicated in influencing the pathology of inflammation induced by H. pylori infection. Currently, several studies have been carried out to investigate the association of IL-1β-511 (rs16944) and IL-1β-31 (rs1143627) polymorphisms with gastritis risk; however, the results are inconsistent and inconclusive. To assess the effect of IL-1β polymorphisms on gastritis susceptibility, we conducted a meta-analysis. Methods: Up to March 15, 2016, 2205 cases and 2289 controls were collected from 12 published case–control studies. Summarized odds ratios and corresponding 95% confidence intervals (CIs) for IL-1β-511 and IL-1β-31 polymorphisms and gastritis risk were estimated using fixed- or random-effects models when appropriate. Heterogeneity was assessed by chi-squared-based Q-statistic test, and the sources of heterogeneity were explored by subgroup analyses and logistic meta-regression analyses. Publication bias was evaluated by Begg funnel plot and Egger test. Sensitivity analyses were also performed. Results: The results provided evidences that the single nucleotide polymorphisms (SNPs) in IL-1β-31 might be associated with the gastritis risk, especially in the Caucasian population, while SNPs in the IL-1β-511 might not be. Conclusion: Our studies may be helpful in supplementing the disease monitoring of gastritis in the future, and additional studies to determine the exact molecular mechanisms might inspire interventions to protect the susceptible subgroups. PMID:28151895

  7. Salivary protein polymorphisms and risk of dental caries: a systematic review.

    Science.gov (United States)

    Lips, Andrea; Antunes, Leonardo Santos; Antunes, Lívia Azeredo; Pintor, Andrea Vaz Braga; Santos, Diana Amado Baptista Dos; Bachinski, Rober; Küchler, Erika Calvano; Alves, Gutemberg Gomes

    2017-06-05

    Dental caries is an oral pathology associated with both lifestyle and genetic factors. The caries process can be influenced by salivary composition, which includes ions and proteins. Studies have described associations between salivary protein polymorphisms and dental caries experience, while others have shown no association with salivary proteins genetic variability. The aim of this study is to assess the influence of salivary protein polymorphisms on the risk of dental caries by means of a systematic review of the current literature. An electronic search was performed in PubMed, Scopus, and Virtual Health Library. The following search terms were used: "dental caries susceptibility," "dental caries," "polymorphism, genetics," "saliva," "proteins," and "peptides." Related MeSH headings and free terms were included. The inclusion criteria comprised clinical investigations of subjects with and without caries. After application of these eligibility criteria, the selected articles were qualified by assessing their methodological quality. Initially, 338 articles were identified from the electronic databases after exclusion of duplicates. Exclusion criteria eliminated 322 articles, and 16 remained for evaluation. Eleven articles found a consistent association between salivary protein polymorphisms and risk of dental caries, for proteins related to antimicrobial activity (beta defensin 1 and lysozyme-like protein), pH control (carbonic anhydrase VI), and bacterial colonization/adhesion (lactotransferrin, mucin, and proline-rich protein Db). This systematic review demonstrated an association between genetic polymorphisms and risk of dental caries for most of the salivary proteins.

  8. Surfactant protein D multimerization and gene polymorphism in COPD and asthma

    DEFF Research Database (Denmark)

    Fakih, Dalia; Akiki, Zeina; Junker, Kirsten

    2018-01-01

    BACKGROUND AND OBJECTIVE: A structural single nucleotide polymorphism rs721917 in the surfactant protein D (SP-D) gene, known as Met11Thr, was reported to influence the circulating levels and degree of multimerization of SP-D and was associated with both COPD and atopy in asthma. Moreover, diseas...

  9. Identification of prion protein gene polymorphisms in goats from Italian scrapie outbreaks

    NARCIS (Netherlands)

    Acutis, P.L.; Bossers, A.; Priem, J.; Riina, M.V.; Peletto, S.; Mazza, M.; Casalone, C.; Forloni, G.; Ru, G.; Caramelli, M.

    2006-01-01

    Susceptibility to scrapie in sheep is influenced by polymorphisms of the prion protein (PrP) gene, whereas no strong association between genetics and scrapie has yet been determined in goats due to the limited number of studies on these animals. In this case¿control study on 177 goats from six

  10. The COMT val158met polymorphism and brain morphometry in healthy young adults

    NARCIS (Netherlands)

    Zinkstok, Janneke; Schmitz, Nicole; van Amelsvoort, Therese; de Win, Maartje; van den Brink, Wim; Baas, Frank; Linszen, Don

    2006-01-01

    Catechol-O-methyltransferase (COMT) is the most important mechanism for dopamine degradation in the prefrontal cortex and contains a functional polymorphism (val(158)met) influencing enzyme activity. The low-activity met allele has been associated with better performance on cognitive tasks relying

  11. On polymorphism of dysprosium trichloride

    Energy Technology Data Exchange (ETDEWEB)

    Zakiryanova, Irina D.; Khokhlov, Vladimir A.; Salyulev, Alexander B.; Korzun, Iraida V. [RAS Ural Branch, Ekaterinburg (Russian Federation). Institute of High-Temperature Electrochemistry

    2015-07-01

    For the first time, the structure of crystalline DyCl{sub 3} over a wide temperature range from room temperature to melting point was studied by Raman spectroscopy. The phonon modes (cm{sup -1}) of dysprosium trichloride (monoclinic crystal lattice of AlCl{sub 3} type, Z = 4, CN = 6) at room temperature are 257 (A{sub 1g}), 201 (E{sub g}), 112 (E{sub g}), 88 (A{sub 1g}), and 63 (E{sub g}). The monoclinic structure of the crystalline DyCl{sub 3} C{sub 2h}{sup 3} symmetry was found to remain constant over the studied temperature range. No polymorphic transformation in the solid state was detected. Gravimetry, calorimetry, and mass spectrometry have been used in addition to support the conclusions made on the basis of Raman spectroscopic data.

  12. On polymorphism of dysprosium trichloride

    International Nuclear Information System (INIS)

    Zakiryanova, Irina D.; Khokhlov, Vladimir A.; Salyulev, Alexander B.; Korzun, Iraida V.

    2015-01-01

    For the first time, the structure of crystalline DyCl 3 over a wide temperature range from room temperature to melting point was studied by Raman spectroscopy. The phonon modes (cm -1 ) of dysprosium trichloride (monoclinic crystal lattice of AlCl 3 type, Z = 4, CN = 6) at room temperature are 257 (A 1g ), 201 (E g ), 112 (E g ), 88 (A 1g ), and 63 (E g ). The monoclinic structure of the crystalline DyCl 3 C 2h 3 symmetry was found to remain constant over the studied temperature range. No polymorphic transformation in the solid state was detected. Gravimetry, calorimetry, and mass spectrometry have been used in addition to support the conclusions made on the basis of Raman spectroscopic data.

  13. No interactions between genetic polymorphisms and stressful life events on outcome of antidepressant treatment

    DEFF Research Database (Denmark)

    Bukh, Jens Drachmann; Bock, Camilla; Vinberg, Maj

    2009-01-01

    Genetic polymorphisms seem to influence the response on antidepressant treatment and moderate the impact of stress on depression. The present study aimed to assess, whether allelic variants and stressful life events interact on the clinical outcome of depression. In a sample of 290 systematically...... recruited patients diagnosed with a single depressive episode according to ICD-10, we assessed the outcome of antidepressant treatment and the presence of stressful life events in a 6-month period preceding onset of depression by means of structured interviews. Further, we genotyped nine polymorphisms...... dependent on stressful life events experienced by the individual prior to onset of depression....

  14. Association of interleukin-1 beta genetic polymorphisms with cognitive performance in elderly females without dementia

    OpenAIRE

    Sasayama, Daimei; Hori, Hiroaki; Teraishi, Toshiya; Hattori, Kotaro; Ota, Miho; Matsuo, Junko; Kawamoto, Yumiko; Kinoshita, Yukiko; Higuchi, Teruhiko; Amano, Naoji; Kunugi, Hiroshi

    2011-01-01

    Interleukin-1 beta (IL-1 beta) is considered to have a role in age-related cognitive decline. A recent study has shown that a promoter polymorphism of the IL-1 beta gene (rs16944) is associated with cognitive performance in elderly males without dementia. In this study, we examined whether polymorphisms of the IL-1 beta gene also influence cognitive functions in elderly females. Cognitive functions were assessed by the Wechsler adult intelligence scale-revised (WAIS-R) in 99 elderly (>= 60 ye...

  15. Genetic polymorphisms of matrix metalloproteinase 3 in primary sclerosing cholangitis

    Science.gov (United States)

    Juran, Brian D.; Atkinson, Elizabeth J.; Schlicht, Erik M.; Larson, Joseph J.; Ellinghaus, David; Franke, Andre; Lazaridis, Konstantinos N.

    2011-01-01

    Background The damaging cholestasis inherent to primary sclerosing cholangitis (PSC) results from bile duct stricturing because of progressive fibrosis. The matrix metalloproteinase 3 (MMP3) degrades a wide range of matrix components and is expressed by activated liver stellate cells, and so is a candidate for involvement with the fibrotic processes underlying PSC. Moreover, the MMP3 gene harbours polymorphisms associated with variation in its activity directly impacting clinical phenotypes. Aims We aimed to examine the influence of MMP3 polymorphisms on PSC risk and progression. Methods Nine single nucleotide polymorphisms (SNPs) tagging the common genetic variation of MMP3 were genotyped in 266 PSC patients and 407 controls. SNPs and inferred haplotypes were assessed for PSC association by logistic regression and score tests. The effect of SNPs on survival to liver transplant or death was analysed using Cox regression, and Kaplan–Meier curves were constructed. Results No association of PSC with individual SNPs or haplotypes of MMP3 was detected. However, progression to death or liver transplant was significantly associated with homozygosity for minor alleles of rs522616, rs650108 and rs683878, particularly among PSC patients with concurrent ulcerative colitis (UC) (strongest in redundant SNPs rs650108/rs683878, hazard ratio = 3.23, 95% confidence interval 1.45–7.25, P = 0.004). Conclusions Genetic variation in MMP3 influences PSC progression, possibly in the context of coexisting UC. While the functional variants and specific mechanisms remain unknown, this finding implicates the turnover of the extracellular matrix as an important and variable component of PSC pathogenesis. Efforts to understand this process could form the basis for developing effective treatments, which are currently lacking for PSC. PMID:21134112

  16. Association between polymorphisms in the TSHR gene and Graves' orbitopathy.

    Directory of Open Access Journals (Sweden)

    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.

  17. Polymorphism Sequence - JSNP | LSDB Archive [Life Science Database Archive metadata

    Lifescience Database Archive (English)

    Full Text Available List Contact us JSNP Polymorphism Sequence Data detail Data name Polymorphism Sequence DOI 10.18908/lsdba.nb...dc00114-001 Description of data contents Information on polymorphisms (SNPs and insertions/deletions) and th...se Name database name JSNP_SNP: single nucleotide polymorphism JSNP_InsDel_IND: insertion/deletion JSNP_InsD...ved allele observed 3' Flanking Sequence 3' flanking sequence Offset in Flanking Sequence position of the polymorphism...uence Accession No. accession No. of the sequence for polymorphism screening Offset in Record position of the polymorphism

  18. Structural and abinitio studies on the polymorphism of iminophosphorane (CH3C6H4)3Pdbnd NP[(dbnd O)(OPh)2

    Science.gov (United States)

    Petric, Mihaela F.; Crisan, Manuela E.; Chumakov, Yurii M.; Varga, Richard A.; Micle, Andreea; Neda, Ion; Ilia, Gheorghe

    2015-03-01

    Two polymorphic forms of a new iminophosphorane have been investigated by infrared, nuclear magnetic resonance and mass spectroscopy, X-ray crystallography and studied through ab initio quantum chemical calculations. The monoclinic polymorph α contains two independent molecules (αI and αII) in the asymmetric unit, while the orthorhombic polymorph ß has one molecule in the asymmetric unit. The molecules in polymorphs α and β adopt different conformations. Hirshfeld surfaces and fingerprint plots were generated in order to compare the two independent molecules αI and αII in the asymmetric unit and also for a comparison of ß molecule, in the orthorhombic crystal system, with the previously reported monoclinic polymorph. The results show that the packing motifs in polymorphs α and β differ mainly due to the redistribution of Csbnd H⋯O and Csbnd H⋯π hydrogen-bond interactions rather than their percentage Hirshfeld surface area contributions. The dipole-dipole interactions significantly influence the intermolecular interactions in polymorphs α and β. The calculated lattice energies indicate that polymorph α is slightly more stable than polymorph α.

  19. [Prevalence of dyslipidemia in middle-aged adults with NOS3 gene polymorphism and low cardiorespiratory fitness].

    Science.gov (United States)

    Malagrino, Pamella A; Sponton, Carlos H G; Esposti, Rodrigo D; Franco-Penteado, Carla F; Fernandes, Romulo A; Bezerra, Marcos André C; Albuquerque, Dulcinéia M; Rodovalho, Cynara M; Bacci, Maurício; Zanesco, Angelina

    2013-02-01

    To evaluate the influence of the interaction between endothelial nitric oxide synthase gene (NOS3) polymorphisms at positions -786T>C, Glu298Asp and intron 4b/a, and cardiorespiratory fitness on plasma nitrite/nitrate levels, blood pressure, lipid profile, and prevalence of cardiometabolic disorders. Ninety-two volunteers were genotyped for NOS3 polymorphisms at positions (-786T>C and Glu298Asp) and (intron 4b/a) and divided according to the genotype: non-polymorphic (NP) and polymorphic (P). After that, they were subdivided according to the cardiorespiratory fitness associated with genotype: high (HNP and HP) and low (LNP and LP). The subjects with polymorphism for the interactions at positions Glu298Asp + intron 4b/a, and Glu298Asp+-786T>C showed the highest values in total cholesterol, as well as dyslipidemia. Our findings show that NOS3 gene polymorphisms at positions -786T>C, Glu298Asp, and intron 4b/a exert negative effects on the lipid profile compared with those who do not carry polymorphisms.

  20. Polymorphism at codon 36 of the p53 gene.

    Science.gov (United States)

    Felix, C A; Brown, D L; Mitsudomi, T; Ikagaki, N; Wong, A; Wasserman, R; Womer, R B; Biegel, J A

    1994-01-01

    A polymorphism at codon 36 in exon 4 of the p53 gene was identified by single strand conformation polymorphism (SSCP) analysis and direct sequencing of genomic DNA PCR products. The polymorphic allele, present in the heterozygous state in genomic DNAs of four of 100 individuals (4%), changes the codon 36 CCG to CCA, eliminates a FinI restriction site and creates a BccI site. Including this polymorphism there are four known polymorphisms in the p53 coding sequence.

  1. DNA polymorphism analysis of Xanthomonas campestris pv ...

    African Journals Online (AJOL)

    strand conformation polymorphism (SSCP) techniques using M13 and 16S rRNA primers, respectively, for genotyping of the phytopathogenic bacterium Xanthomonas campestris pv. campestris was studied. RAPD provided a simple, rapid, and ...

  2. Complementary DNA-amplified fragment length polymorphism ...

    African Journals Online (AJOL)

    Complementary DNA-amplified fragment length polymorphism (AFLP-cDNA) analysis of differential gene expression from the xerophyte Ammopiptanthus mongolicus in response to cold, drought and cold together with drought.

  3. Genetic diversity among sorghum landraces and polymorphism ...

    African Journals Online (AJOL)

    breeding program through marker-assisted selection. ... Keywords: Sorghum, diversity, stay-green trait, marker, polymorphism. ..... Na: Number of different alleles; Na Freq: Frequency of different alleles; Ne: Number of effective alleles; ...

  4. Polymorphous light eruption - some interesting aspects

    International Nuclear Information System (INIS)

    Corrales-Padilla, H.; Dominguez-Soto, L.; Hojyo-Tomoka, M.T.; Londono, F.; Vargas-Ocampo, F.

    1979-01-01

    A study of polymorphous light eruption (PLE) is Latin America is reported. The clinical lesions, the course, histopathology, differential diagnosis, pathogenesis, treatment and systemic photoprotection are discussed. Treatment with ultraviolet radiation is included. (C.F.)

  5. An association study between polymorphism of alcohol ...

    African Journals Online (AJOL)

    Jane

    2011-09-28

    Sep 28, 2011 ... factors which include alcohol metabolizing genes and ... Association research proves that c2 allele is a risk factor for ..... polymorphism in alcohol liver cirrhosis and alcohol chronic pancreatitis among Polish individuals.S cand ...

  6. Eighteen polymorphic microsatellites for domestic pigeon Columba ...

    Indian Academy of Sciences (India)

    certain parasites which cause health problems in humans and domestic animals ... The genomic DNA was isolated using standard protocol as described by ..... panel of polymorphic microsatellite markers in Himalayan monal. Lophophorus ...

  7. Contrasting genetic influence of PON 1 coding gene polymorphisms ...

    African Journals Online (AJOL)

    Nadia Youssef Sadek Morcos

    2015-03-31

    Mar 31, 2015 ... toxicity primarily by inhibiting the enzyme acetylcholinesterase. (AChE) [1]. ... 3. Methods. DNA was extracted from whole blood using a QIAamp Blood .... activity. It is not clear whether this is because of a decreased stability of ...

  8. (ERβ) polymorphism and its influence on breast cancer risk

    Indian Academy of Sciences (India)

    2009-08-03

    Aug 3, 2009 ... development and maintenance of female sexual characters in humans. ... Low percentage of epithelial cells (7%–10%) in normal human breast express ... associated with increased likelihood of good response to en-.

  9. Haptoglobin gene polymorphism influences the effect of malaria ...

    African Journals Online (AJOL)

    uwerhiavwe

    2013-03-06

    Mar 6, 2013 ... ... to detect parasitemia. Higher plasma haptoglobin level tended to be associated ... malaria in pregnant mothers and children up to five years of age. Participants were .... complications of malaria disease. Elagib et al. (1998).

  10. Lymphotoxin-alpha polymorphisms and presence of cancer in 1,536 consecutive autopsy cases

    Directory of Open Access Journals (Sweden)

    Muramatsu Masaaki

    2008-08-01

    Full Text Available Abstract Background Lymphotoxin-alpha (LTA is a pro-inflammatory cytokine with anti-tumor activity. The objective of this study was to determine whether LTA polymorphisms influence the presence of cancer. Methods LTA polymorphisms C804A (rs1041981, T60N and T495C (rs2229094, C13R were determined in 1,536 consecutive autopsy cases and were registered in the Japanese single-nucleotide polymorphisms (SNPs for geriatric research (JG-SNP Internet database. Tumors were systematically reviewed, pathologically confirmed, and assessed in relation to LTA genotype. Results The study population consisted of 827 males and 709 females, with a mean age of 80 years. Altogether, we studied 606 subjects without cancer and 930 subjects with cancer of the stomach (n = 183, lung (n = 164, colon or rectum (n = 143, or other sites. The presence of cancer was higher in males than in females. The C804A and T495C polymorphisms were associated with cancer in males (CA + AA: CC, adjusted OR = 0.72, 95% CI = 0.53 – 0.99; TC + CC: TT, adjusted OR = 1.45, 95% CI = 1.04 – 2.02; respectively but not in females. In males, the C804A polymorphism was associated with lung cancer (CA + AA: CC, adjusted OR = 0.60, 95% CI = 0.37 – 0.97, whereas the T495C polymorphism was associated with gastric cancer (TC + CC: TT, adjusted OR = 1.68, 95% CI = 1.06 – 2.65. Conclusion We found some evidence of an association between LTA polymorphisms and cancer risk in elderly Japanese men. Further studies in larger populations should examine this hypothesis.

  11. Letter regarding Li JS et al. entitled "ERCC polymorphisms and prognosis of patients with osteosarcoma".

    Science.gov (United States)

    Jian, Yuekui; Tian, Xiaobin; Li, Bo; Zhou, Zhuojia; Wu, Xinglin

    2015-05-01

    With great interest, we read the article "ERCC polymorphisms and prognosis of patients with osteosarcoma" (by Li JS et al.), which has reached important conclusions about the relationship between ERCC polymorphisms and osteosarcoma prognosis. Through quantitative analysis, the meta-analysis showed that ERCC2 Lys751Gln (ORGG vs. AA = 0.40 (95%CI = 0.1-0.86), P heterogeneity = 0.502; I (2) = 0 %) and ERCC5 His46His (ORCC vs. TT = 0.37 (95%CI = 0.15-0.93), P heterogeneity = 0.569; I (2) = 0 %) polymorphisms might influence the prognosis of patients with osteosarcoma [1]. The meta-analysis results are encouraging. Nevertheless, some deficiencies still existed that we would like to raise.

  12. Interaction between genetic polymorphisms and stressful life events in first episode depression

    DEFF Research Database (Denmark)

    Bukh, Jens Drachmann; Bock, Camilla; Vinberg, Maj

    2009-01-01

    of depression among participants. METHOD: We applied a case-only design, including 290 ethnically homogeneous patients suffering exclusively from first episode depression. Psychiatric mo-morbidity, personality traits and disorders and stressful life events in a six months period preceding onset of depression......BACKGROUND: A polymorphism in the serotonin transporter (5-HTT) gene seems to moderate the influence of stressful life events on depression. However, the results from previous studies of gene-environment interactions in depression are inconsistent and might be confounded by the history......A, 2A, and 2C. RESULTS: The low activity variants of the 5-HTT-linked polymorphic region in the serotonin transporter gene and the Met-allele of a single nucleotide polymorphism (Val66Met) in the gene encoding brain derived neurotrophic factor were independently associated with the presence...

  13. PON1 promoter polymorphisms contribute to PCOS susceptibility and phenotypic outcomes in Indian women.

    Science.gov (United States)

    Dadachanji, Roshan; Shaikh, Nuzhat; Patil, Anushree; Shah, Nalini; Mukherjee, Srabani

    2018-06-30

    Polycystic ovary syndrome is a common endocrinopathy characterized by anovulatory infertility, hyperandrogenism, insulin resistance and oxidative stress, which predisposes affected women to reproductive and cardiometabolic complications in later life. We have investigated the association of PON1 promoter polymorphisms with PCOS susceptibility, PON1 activity and its related traits in Indian women. The genotypic and allelic frequency distribution of only -907G/C polymorphism in PON1 promoter showed significant difference between non-hyperandrogenic control and PCOS women, and was significantly associated with reduced susceptibility to PCOS, considering the recessive model. PON1 lactonase and arylesterase activities were also significantly decreased in women with PCOS compared to controls. Further, PON1 promoter polymorphisms were linked to altered insulin and testosterone levels in hyperandrogenic and non-hyperandrogenic women with PCOS. This study highlights PON1 as an important candidate gene influencing genetic pathophysiology of PCOS. Copyright © 2018 Elsevier B.V. All rights reserved.

  14. Effect of BCHE single nucleotide polymorphisms on lipid metabolism markers in women

    Directory of Open Access Journals (Sweden)

    Jéssica de Oliveira

    2017-05-01

    Full Text Available Abstract Butyrylcholinesterase (BChE activity and polymorphisms in its encoding gene had previously been associated with metabolic traits of obesity. This study investigated the association of three single nucleotide polymorphisms (SNPs in the BCHE gene: -116G > A (rs1126680, 1615GA (rs1803274, 1914A 0.05. The dominant and recessive models were tested, and different effects were found. The -116A allele showed a dominant effect in BChE activity reduction in both non-obese and obese women (p = 0.045 and p G and 1615GA SNPs influenced the TG levels only in obese women. The 1914G and the 1615A alleles were associated with decreased plasma levels of TG. Thus, our results suggest that the obesity condition, characterized by loss of energy homeostasis, is modulated by BCHE polymorphisms.

  15. Association of TLR1, TLR2, TLR4, TLR6, and TIRAP polymorphisms with disease susceptibility.

    Science.gov (United States)

    Noreen, Mamoona; Arshad, Muhammad

    2015-06-01

    Toll like receptors (TLRs) play a crucial role in regulation of innate as well as adaptive immunity. TLRs recognize a distinct but limited repertoire of conserved microbial products. Ligand binding to TLRs activates the signaling cascade and results in activation of multiple inflammatory genes. Variation in this immune response is under genetic control. Polymorphisms in genes associated with inflammatory pathway especially influence the outcome of diseases. TLR2 makes heterodimer with TLR1 or TLR6 and recognizes a wide variety of microbial ligands. In this review, we summarize studies of polymorphisms in genes encoding TLR1, TLR2, TLR4, TLR6, and most polymorphic adaptor protein, Mal/TIRAP, revealing their effect on susceptibility to diseases.

  16. Modeling dynamic beta-gamma polymorphic transition in Tin

    Science.gov (United States)

    Chauvin, Camille; Montheillet, Frank; Petit, Jacques; CEA Gramat Collaboration; EMSE Collaboration

    2015-06-01

    Solid-solid phase transitions in metals have been studied by shock waves techniques for many decades. Recent experiments have investigated the transition during isentropic compression experiments and shock-wave compression and have highlighted the strong influence of the loading rate on the transition. Complementary data obtained with velocity and temperature measurements around the polymorphic transition beta-gamma of Tin on gas gun experiments have displayed the importance of the kinetics of the transition. But, even though this phenomenon is known, modeling the kinetic remains complex and based on empirical formulations. A multiphase EOS is available in our 1D Lagrangian code Unidim. We propose to present the influence of various kinetic laws (either empirical or involving nucleation and growth mechanisms) and their parameters (Gibbs free energy, temperature, pressure) on the transformation rate. We compare experimental and calculated velocities and temperature profiles and we underline the effects of the empirical parameters of these models.

  17. Association Between Genetic Polymorphisms in the Serotonergic System and Comorbid Personality Disorders Among Patients with First-Episode Depression

    DEFF Research Database (Denmark)

    Bukh, Jens D; Bock, Camilla; Kessing, Lars V

    2014-01-01

    Studies on the association between genetic polymorphisms and personality disorders have provided inconsistent results. Using the "enriched sample method," the authors of the present study aimed to assess the association between polymorphisms in the serotonergic transmitter system and comorbid...... personality disorders in patients recently diagnosed with first-episode depression. A total of 290 participants were systematically recruited via the Danish Psychiatric Central Research Register. Diagnoses of personality disorders were assessed by a SCID-II interview, and polymorphisms in the genes encoding...... the serotonin transporter, serotonin receptors 1A, 2A, 2C, and tryptophan hydroxylase 1 were genotyped. The authors found a significant effect of the length polymorphism in the serotonin transporter gene (5-HTTLPR) on cluster B personality disorder (mainly borderline disorder), but no influence on cluster C...

  18. The-1131T > C Polymorphism in the Apolipoprotein A5 Gene is Related to Hypertriglyceridemia in Taiwanese Aborigines

    Directory of Open Access Journals (Sweden)

    Meng-Chuan Huang

    2008-04-01

    Full Text Available The prevalence of hypertriglyceridemia, considered to be an independent risk factor for the development of cardiovascular disease, is high in Taiwanese aborigines. This study was undertaken to examine the effect of the -1131T > C polymorphism in the apolipoprotein A5 gene on serum triglyceride levels in female Taiwanese aborigines. This was a cross-sectional study, and a total of 316 unrelated female Taiwanese aborigines were genotyped at the -1131T > C polymorphism in apolipoprotein A5 using the polymerase chain reaction-restriction fragment length polymorphism method. Serum triglyceride ≥150 mg/dL was defined as the hypertriglyceridemia group and triglyceride C polymorphism of the Apo A5 gene influences serum triglyceride levels in female Taiwanese aborigines, and that differences exist in the frequency of the C allele among people of various ethnicities.

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

    Directory of Open Access Journals (Sweden)

    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.

  20. Insulin gene polymorphisms in type 1 diabetes, Addison's disease and the polyglandular autoimmune syndrome type II

    Directory of Open Access Journals (Sweden)

    Hahner Stefanie

    2008-07-01

    Full Text Available Abstract Background Polymorphisms within the insulin gene can influence insulin expression in the pancreas and especially in the thymus, where self-antigens are processed, shaping the T cell repertoire into selftolerance, a process that protects from β-cell autoimmunity. Methods We investigated the role of the -2221Msp(C/T and -23HphI(A/T polymorphisms within the insulin gene in patients with a monoglandular autoimmune endocrine disease [patients with isolated type 1 diabetes (T1D, n = 317, Addison's disease (AD, n = 107 or Hashimoto's thyroiditis (HT, n = 61], those with a polyglandular autoimmune syndrome type II (combination of T1D and/or AD with HT or GD, n = 62 as well as in healthy controls (HC, n = 275. Results T1D patients carried significantly more often the homozygous genotype "CC" -2221Msp(C/T and "AA" -23HphI(A/T polymorphisms than the HC (78.5% vs. 66.2%, p = 0.0027 and 75.4% vs. 52.4%, p = 3.7 × 10-8, respectively. The distribution of insulin gene polymorphisms did not show significant differences between patients with AD, HT, or APS-II and HC. Conclusion We demonstrate that the allele "C" of the -2221Msp(C/T and "A" -23HphI(A/T insulin gene polymorphisms confer susceptibility to T1D but not to isolated AD, HT or as a part of the APS-II.

  1. Quantitating PrP Polymorphisms Present in Prions from Heterozygous Scrapie-Infected Sheep.

    Science.gov (United States)

    Silva, Christopher J; Erickson-Beltran, Melissa L; Hui, Colleen; Badiola, Juan José; Nicholson, Eric M; Requena, Jesús R; Bolea, Rosa

    2017-01-03

    Scrapie is a prion (PrP Sc ) disease of sheep. The incubation period of sheep scrapie is strongly influenced by polymorphisms at positions 136, 154, and 171 of a sheep's normal cellular prion protein (PrP C ). Chymotrypsin was used to digest sheep recombinant PrP to identify a set of characteristic peptides [M 132 LGSXMSRPL 141 (X = A or V), Y 153 XENMY 158 (X,= H or R), and Y 166 RPVDXY 172 (X = H, K, Q, or R)] that could be used to detect and quantitate polymorphisms at positions 136, 154, and 171 of sheep PrP C or PrP Sc . These peptides were used to develop a multiple reaction monitoring method (MRM) to detect the amounts of a particular polymorphism in a sample of PrP Sc isolated from sheep heterozygous for their PrP C proteins. The limit of detection for these peptides was less than 50 attomole. Spinal cord tissue from heterozygous (ARQ/VRQ or ARH/ARQ) scrapie-infected Rasa Aragonesa sheep was analyzed using this MRM method. Both sets of heterozygotes show the presence of both polymorphisms in PrP Sc . This was true for samples containing both proteinase K (PK)-sensitive and PK-resistant PrP Sc and samples containing only the PK-resistant PrP Sc . These results show that heterozygous animals contain PrP Sc that is composed of significant amounts of both PrP polymorphisms.

  2. ACE Insertion/Deletion Polymorphism and Diabetic Nephropathy: Clinical Implications of Genetic Information

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    Sung-Kyu Ha

    2014-01-01

    Full Text Available Approximately 20–40% of diabetic patients develop nephropathy which is the leading cause of ESRD in developed countries. The ACE I/D polymorphism is thought to be a marker for functional polymorphism which regulates circulating and tissue ACE activity. While the initial study found a protective effect of the II genotype on the development of nephropathy in IDDM patients, subsequent studies have addressed the role of ACE I/D polymorphism in the development and progression of diabetic nephropathy. RAAS blockers are the first line drugs for the treatment hypertension associated with diabetes and have been widely used in everyday clinical practice for the purpose of reducing proteinuria in patients with various renal diseases. However, the antiproteinuric effect of RAAS blockers is variable and the percentage of reducing proteinuria is in the range of 20–80%. The antiproteinuric effect of RAAS blockers may be related to a number of factors: the type or the dose of RAAS blockers, the duration of therapy, the level of sodium intake, and the type of patient’s ACE I/D genotype. Besides the nongenetic factors, drug responses, can be influenced by ACE gene polymorphism. In this review, we discuss the relationship between ACE I/D polymorphism and diabetic nephropathy and therapeutic response of RAAS blockers.

  3. DNA repair gene polymorphisms in relation to chromosome aberration frequencies in retired radiation workers

    International Nuclear Information System (INIS)

    Wilding, Craig S.; Relton, Caroline L.; Rees, Gwen S.; Tarone, Robert E.; Whitehouse, Caroline A.; Tawn, E. Janet

    2005-01-01

    Polymorphic variation in DNA repair genes was examined in a group of retired workers from the British Nuclear Fuels plc facility at Sellafield in relation to previously determined translocation frequencies in peripheral blood lymphocytes. Variation at seven polymorphisms in four genes involved in the base excision repair (XRCC1 R194W, R399Q and a [AC] n microsatellite in the 3' UTR) and double strand break repair (XRCC3 T241M and a [AC] n microsatellite in intron 3 of XRCC3, XRCC4 I134T, and a GACTAn microsatellite located 120kb 5' of XRCC5) pathways was determined for 291 retired radiation workers who had received cumulative occupational external radiation doses of between 0 and 1873mSv. When the interaction between radiation dose and each DNA repair gene polymorphism was examined in relation to translocation frequency there was no evidence for any of the polymorphisms studied influencing the response to occupational exposure. A positive interaction observed between genotype (individuals with at least one allele >=20 repeat units) at a microsatellite locus in the XRCC3 gene and smoking status should be interpreted cautiously because interactions were investigated for seven polymorphisms and two exposures. Nonetheless, further research is warranted to examine whether this DNA repair gene variant might be associated with a sub-optimal repair response to smoking-induced DNA damage and hence an increased frequency of translocations

  4. The association of folate pathway and DNA repair polymorphisms with susceptibility to childhood acute lymphoblastic leukemia.

    Science.gov (United States)

    Goričar, Katja; Erčulj, Nina; Faganel Kotnik, Barbara; Debeljak, Maruša; Hovnik, Tinka; Jazbec, Janez; Dolžan, Vita

    2015-05-15

    Genetic factors may play an important role in susceptibility to childhood acute lymphoblastic leukemia (ALL). The aim of our study was to evaluate the associations of genetic polymorphisms in folate pathway and DNA repair genes with susceptibility to ALL. In total, 121 children with ALL and 184 unrelated healthy controls of Slovenian origin were genotyped for 14 polymorphisms in seven genes of folate pathway, base excision repair and homologous recombination repair (TYMS, MTHFR, OGG1, XRCC1, NBN, RAD51, and XRCC3). In addition, the exon 6 of NBN was screened for the presence of mutations using denaturing high performance liquid chromatography. Twelve polymorphisms were in Hardy-Weinberg equilibrium in controls and their genotype frequencies were in agreement with those reported in other Caucasian populations. Among the investigated polymorphisms and mutations, NBN Glu185Gln significantly decreased susceptibility to B-cell ALL (p=0.037), while TYMS 3R allele decreased susceptibility to T-cell ALL (p=0.011). Moreover, significantly decreased susceptibility to ALL was observed for MTHFR TA (p=0.030) and RAD51 GTT haplotypes (p=0.016). Susceptibility to ALL increased with the increasing number of risk alleles (ptrend=0.007). We also observed significant influence of hOGG-RAD51 and NBN-RAD51 interactions on susceptibility to ALL. Our results suggest that combination of several polymorphisms in DNA repair and folate pathways may significantly affect susceptibility to childhood ALL. Copyright © 2015 Elsevier B.V. All rights reserved.

  5. Interleukin gene polymorphisms and breast cancer: a case control study and systematic literature review

    International Nuclear Information System (INIS)

    Balasubramanian, SP; Azmy, IAF; Higham, SE; Wilson, AG; Cross, SS; Cox, A; Brown, NJ; Reed, MW

    2006-01-01

    Interleukins and cytokines play an important role in the pathogenesis of many solid cancers. Several single nucleotide polymorphisms (SNPs) identified in cytokine genes are thought to influence the expression or function of these proteins and many have been evaluated for their role in inflammatory disease and cancer predisposition. The aim of this study was to evaluate any role of specific SNPs in the interleukin genes IL1A, IL1B, IL1RN, IL4R, IL6 and IL10 in predisposition to breast cancer susceptibility and severity. Candidate single nucleotide polymorphisms (SNPs) in key cytokine genes were genotyped in breast cancer patients and in appropriate healthy volunteers who were similar in age, race and sex. Genotyping was performed using a high throughput allelic discrimination method. Data on clinico-pathological details and survival were collected. A systematic review of Medline English literature was done to retrieve previous studies of these polymorphisms in breast cancer. None of the polymorphisms studied showed any overall predisposition to breast cancer susceptibility, severity or to time to death or occurrence of distant metastases. The results of the systematic review are summarised. Polymorphisms within key interleukin genes (IL1A, IL1B, IL1RN, IL4R, IL6 and IL10 do not appear to play a significant overall role in breast cancer susceptibility or severity

  6. Analysis of CYP1A1 and COMT polymorphisms in women with cervical cancer.

    Science.gov (United States)

    Kleine, J P; Camargo-Kosugi, C M; Carvalho, C V; Silva, F C; Silva, I D C G

    2015-12-29

    The aim of this case-control study was to obtain a comprehensive panel of genetic polymorphisms present only in genes (cytochrome P-450 1A1--CYP1A1 and catechol-O-methyl transferase--COMT) within the metabolic pathway of sex steroids and determine their possible associations with the presence or absence of cervical cancer. Genotypes of 222 women were analyzed: a) 81 with cancer of the cervix treated at the Cancer Hospital Alfredo Abram, between June 2012 and May 2013, with diagnosis confirmed surgically and/or through histomorphological examination; and b) 141 healthy women who assisted at the Endocrine Gynecology and Climacteric Ambulatory, Department of Gynecology, UNIFESP-EPM. These polymorphisms were detected by polymerase chain reaction amplification-restriction fragment length polymorphism analysis and visualized on 3% agarose gels stained with ethidium bromide. We found a significant association between the frequency of the CYP1A1 polymorphism and the development of cervical cancer. A statistical difference was observed between patient and control groups for CYP1A1 polymorphism genotype distributions (P 0.05) or between other risk variables analyzed. The CYP1A1 gene involved in the metabolic pathway of sex steroids might influence the emergence of pathological conditions such as cervical cancer in women who carry a mutated allele, and result in 1.80 and 13.46 times increased risk for women with heterozygous or homozygous mutated genotypes, respectively.

  7. Polymorphism in Bacterial Flagella Suspensions

    Science.gov (United States)

    Schwenger, Walter J.

    Bacterial flagella are a type of biological polymer studied for its role in bacterial motility and the polymorphic transitions undertaken to facilitate the run and tumble behavior. The naturally rigid, helical shape of flagella gives rise to novel colloidal dynamics and material properties. This thesis studies methods in which the shape of bacterial flagella can be controlled using in vitro methods and the changes the shape of the flagella have on both single particle dynamics and bulk material properties. We observe individual flagellum in both the dilute and semidilute regimes to observe the effects of solvent condition on the shape of the filament as well as the effect the filament morphology has on reptation through a network of flagella. In addition, we present rheological measurements showing how the shape of filaments effects the bulk material properties of flagellar suspensions. We find that the individual particle dynamics in suspensions of flagella can vary with geometry from needing to reptate linearly via rotation for helical filaments to the prevention of long range diffusion for block copolymer filaments. Similarly, for bulk material properties of flagella suspensions, helical geometries show a dramatic enhancement in elasticity over straight filaments while block copolymers form an elastic gel without the aid of crosslinking agents.

  8. Polymorphism of the glucocorticoid receptor gene appears to have limited impact in patients with Addison's disease.

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    Ian Louis Ross

    Full Text Available BACKGROUND: Addison's disease (AD has been associated with an increased risk of cardiovascular disease. Glucocorticoid receptor polymorphisms that alter glucocorticoid sensitivity may influence metabolic and cardiovascular risk factors in patients with AD. The 9β polymorphism of the glucocorticoid receptor gene is associated with relative glucocorticoid resistance and has been reported to increase the risk of myocardial infarction in the elderly. We explored the impact of this polymorphism in patients with AD. MATERIALS AND METHODS: 147 patients with AD and 147 age, gender and ethnicity matched healthy controls were recruited. Blood was taken in a non-fasted state for plasma lipid determination, measurement of cardiovascular risk factors and DNA extraction. RESULTS: Genotype data for the 9β polymorphism was available for 139 patients and 146 controls. AD patients had a more atherogenic lipid profile characterized by an increase in the prevalence of small dense LDL (p = 0.003, increased triglycerides (p = 0.002, reduced HDLC (p<0.001 an elevated highly sensitive C-reactive protein (p = 0.01, compared with controls. The 9β polymorphism (at least one G allele was found in 28% of patients and controls respectively. After adjusting for age, gender, ethnicity, BMI and hydrocortisone dose per metre square of body surface area in patients, there were no significant metabolic associations with this polymorphism and hydrocortisone doses were not higher in patients with the polymorphism. CONCLUSIONS: This study did not identify any associations between the 9β polymorphism and cardiovascular risk factors or hydrocortisone dose and determination of this polymorphism is therefore unlikely to be of clinical benefit in the management of patients with AD.

  9. Polymorphism of the Glucocorticoid Receptor Gene Appears to Have Limited Impact in Patients with Addison’s Disease

    Science.gov (United States)

    Ross, Ian Louis; Dandara, Collet; Swart, Marelize; Lacerda, Miguel; Schatz, Desmond; Blom, Dirk Jacobus

    2014-01-01

    Background Addison’s disease (AD) has been associated with an increased risk of cardiovascular disease. Glucocorticoid receptor polymorphisms that alter glucocorticoid sensitivity may influence metabolic and cardiovascular risk factors in patients with AD. The 9β polymorphism of the glucocorticoid receptor gene is associated with relative glucocorticoid resistance and has been reported to increase the risk of myocardial infarction in the elderly. We explored the impact of this polymorphism in patients with AD. Materials and Methods 147 patients with AD and 147 age, gender and ethnicity matched healthy controls were recruited. Blood was taken in a non-fasted state for plasma lipid determination, measurement of cardiovascular risk factors and DNA extraction. Results Genotype data for the 9β polymorphism was available for 139 patients and 146 controls. AD patients had a more atherogenic lipid profile characterized by an increase in the prevalence of small dense LDL (p = 0.003), increased triglycerides (p = 0.002), reduced HDLC (p<0.001) an elevated highly sensitive C-reactive protein (p = 0.01), compared with controls. The 9β polymorphism (at least one G allele) was found in 28% of patients and controls respectively. After adjusting for age, gender, ethnicity, BMI and hydrocortisone dose per metre square of body surface area in patients, there were no significant metabolic associations with this polymorphism and hydrocortisone doses were not higher in patients with the polymorphism. Conclusions This study did not identify any associations between the 9β polymorphism and cardiovascular risk factors or hydrocortisone dose and determination of this polymorphism is therefore unlikely to be of clinical benefit in the management of patients with AD. PMID:24466047

  10. Arg753gln and Arg677 Trp Polymorphisms of Toll-Like Receptor 2 In Acute Apical Abscess.

    Science.gov (United States)

    Miri-Moghaddam, Ebrahim; Farhad Mollashahi, Narges; Naghibi, Nava; Garme, Yasaman; Bazi, Ali

    2018-06-01

    Genetic polymorphisms can alter immunity response against pathogens, which in turn influence individuals' susceptibility to certain infections. Our aim was to determine the association of Arg753Gln (rs5743708) and Arg677Trp (rs12191786) polymorphisms of toll like receptor-2 gene with the two clinical forms of apical periodontitis: acute apical abscess (AAA) and asymptomatic apical periodontitis (AAP). There were 50 patients with AAA as case group and 50 with AAP as control group. Genotyping was done using Tetra-ARMS (amplification refractory mutation system) PCR. Heterozygous genotype of Arg677Trp polymorphism was associated with risk of AAA (OR=1.9, 95% CI: 0.7-5.5, p = 0.05). Although statistically insignificant, Arg677Trp polymorphism promoted the risk of AAA in dominant model (OR=2.1, 95% CI: 0.7-5.9, p > 0.05). The frequency of mutant allele (T) of Arg677Trp polymorphism was higher in AAA (14%) than AAP (7%) subjects (OR=1.7, 95% CI: 0.6-4.7). For Arg753Gln polymorphism, wild homozygous (GG) represented the dominant genotype in both cases (96%) and controls (100%). Variant allele (A) of Arg753Gln polymorphism was identified in 2% of AAA, while no individual represented with this allele in AAP subjects. Individuals with Arg753Gln; Arg677Trp (GG; TC) combination showed an elevated risk of AAA (OR=1.6, 95% CI: 0.5- 4.2, p > 0.05). Arg677Trp polymorphism of TLR-2 rendered a higher risk for the development of abscesses in apical periodontitis. It is recommended to explore role of this polymorphism in other populations.

  11. No association of the neuropeptide Y (Leu7Pro) and ghrelin gene (Arg51Gln, Leu72Met, Gln90Leu) single nucleotide polymorphisms with eating disorders.

    Science.gov (United States)

    Kindler, Jochen; Bailer, Ursula; de Zwaan, Martina; Fuchs, Karoline; Leisch, Friedrich; Grün, Bettina; Strnad, Alexandra; Stojanovic, Mirjana; Windisch, Julia; Lennkh-Wolfsberg, Claudia; El-Giamal, Nadja; Sieghart, Werner; Kasper, Siegfried; Aschauer, Harald

    2011-06-01

    Genetic factors likely contribute to the biological vulnerability of eating disorders. Case-control association study on one neuropeptide Y gene (Leu7Pro) polymorphism and three ghrelin gene (Arg51Gln, Leu72Met and Gln90Leu) polymorphisms. 114 eating disorder patients (46 with anorexia nervosa, 30 with bulimia nervosa, 38 with binge eating disorder) and 164 healthy controls were genotyped. No differences were detected between patients and controls for any of the four polymorphisms in allele frequency and genotype distribution (P > 0.05). Allele frequencies and genotypes had no significant influence on body mass index (P > 0.05) in eating disorder patients. Positive findings of former case-control studies of associations between ghrelin gene polymorphisms and eating disorders could not be replicated. Neuropeptide Y gene polymorphisms have not been investigated in eating disorders before.

  12. THE ASSOCIATION OF GENE POLYMORPHISMS WITH ATHLETE STATUS IN UKRAINIANS

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    Svitlana B. Drozdovska

    2013-06-01

    Full Text Available Athletic performance is a polygenic trait influenced by both environmental and genetic factors. Objective: to investigate individually and in combination the association of common gene polymorphisms with athlete status in Ukrainians. Methods: A total of 210 elite Ukrainian athletes (100 endurance-oriented and 110 power-orientated athletes and 326 controls were genotyped for ACE I/D, HIF1A Pro582Ser, NOS3 –786 T/C, PPARA intron 7 G/C, PPARG Pro12Ala and PPARGC1B Ala203Pro gene polymorphisms, most of which were previously reported to be associated with athlete status or related intermediate phenotypes in different populations. Results: Power-oriented athletes exhibited an increased frequency of the HIF1A Ser (16.1 vs. 9.420P = 0.034 and NOS3 T alleles (78.3 vs. 66.220P = 0.0019 in comparison with controls. Additionally, we found that the frequency of the PPARG Ala allele was significantly higher in power-oriented athletes compared with the endurance-oriented athletes (24.7 vs. 13.520P = 0.0076. Next, we determined the total genotype score (TGS, from the accumulated combination of the three polymorphisms, with a maximum value of 100 for the theoretically optimal polygenic score in athletes and controls. The mean TGS was significantly higher in power-oriented athletes (39.1 ± 2.3 vs. 32.6 ± 1.5; P = 0.0142 than in controls. Conclusions: We found that the HIF1A Ser, NOS3 T and PPARG Ala alleles were associated with power athlete status in Ukrainians.

  13. 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.

  14. TNF-α -238, -308, -863 polymorphisms, and brucellosis infection.

    Science.gov (United States)

    Eskandari-Nasab, Ebrahim; Moghadampour, Mehdi; Sepanj-Nia, Adel

    2016-01-01

    Brucella abortus is an intracellular bacterium that affects humans and domestic animals. Tumor necrosis factor-alpha (TNF-α) has been shown as a key player in the induction of cell-mediated resistance against Brucella infection. We aimed to evaluate the possible influence of the TNF-α promoter polymorphisms (-308 G/A, -238 G/A, and -863 C/A) on the susceptibility of human brucellosis. A total of 153 patients with active brucellosis and 128 healthy individuals were recruited. All subjects were genotyped for the polymorphisms in the TNF-α gene by Allele-Specific polymerase chain reaction analysis. Our results showed that the TNF-α -308 GG genotype was significantly more frequently present in controls than in brucellosis patients (91% vs. 75%), thus was a protective factor against developing brucellosis (OR=0.313, p=0.001). In contrast, the -308 GA genotype (OR=3.026, p=0.002) and minor allele (A) (OR=3.058, p=0.001) as well as AAG haplotype (OR=4.014, p=0.001) conferred an increased risk of brucellosis. However, the -238 G/A and -863 C/A polymorphisms were not associated with the risk of brucellosis at both allelic and genotypic levels (p>0.05). Our study revealed that the TNF-α -308 A allele or GA heterozygosity or AAG haplotype were associated with an increased risk of brucellosis in our population. Copyright © 2015 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved.

  15. The pattern of polymorphism in Arabidopsis thaliana.

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    2005-07-01

    Full Text Available We resequenced 876 short fragments in a sample of 96 individuals of Arabidopsis thaliana that included stock center accessions as well as a hierarchical sample from natural populations. Although A. thaliana is a selfing weed, the pattern of polymorphism in general agrees with what is expected for a widely distributed, sexually reproducing species. Linkage disequilibrium decays rapidly, within 50 kb. Variation is shared worldwide, although population structure and isolation by distance are evident. The data fail to fit standard neutral models in several ways. There is a genome-wide excess of rare alleles, at least partially due to selection. There is too much variation between genomic regions in the level of polymorphism. The local level of polymorphism is negatively correlated with gene density and positively correlated with segmental duplications. Because the data do not fit theoretical null distributions, attempts to infer natural selection from polymorphism data will require genome-wide surveys of polymorphism in order to identify anomalous regions. Despite this, our data support the utility of A. thaliana as a model for evolutionary functional genomics.

  16. PRDM16 Gene Polymorphism Is Associated with Obesity and Blood Lipids Profiles in Saudi Population

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    Aishah AlAmrani

    2018-06-01

    Full Text Available Aims: The PR domain containing 16 (PRDM16 gene and the Phosphodiesterase 4D (PDE4 gene are both an essential regulators in the thermogenesis process in the brown adipose tissues (BAT. The influence of polymorphisms in those genes on obesity and blood lipids profile is unknown particularly in the Saudi population, so the current study is aiming to explore that. Methods: A case control format was used that involved 89 obese individual and 84 non-obese (control. The PRDM16 (rs2651899 and PDE4D (rs295978 polymorphisms were genotyped using KASP™ (Competitive Allele-Specific PCR method. Results: The distributions of the AA, GG, and AG genotypes of PRDM16 (rs2651899 polymorphism were 0.19, 0.26 and 0.54, respectively. While the distribution of the mutated allele A was 0.7 in the obese group comparing to 0.34 in the non-obese group. Participants with the mutated genotypes, AA and AG, of PRDM16 (rs2651899 polymorphism were significantly more likely to be obese as compared to participants with wild type genotype (OR = 21, 95% CI = 5.4190 to 84.4231, p value < 0.0001 and OR = 44.6, 95% CI = 11.5984 to 172.0157, p value < 0.0001, respectively. The wild type GG genotype of this polymorphism was associated with higher blood cholesterol, HDL and LDL but lower blood triglyceride compared with the mutated genotypes (p = 0.003, p = 0.008, p = 0.02 and p = 0.003, respectively. In contrast, PDE4D (rs295978 polymorphism was not associated with risk of obesity and had no effects on blood lipids profile. Conclusions: We found that the PRDM16 polymorphism (rs2651899 is a risk factor for obesity and influence blood lipids profiles significantly in Saudi population. While the PDE4D (rs295978 polymorphism didn’t show significant effect on risk of obesity or blood lipids profiles.

  17. 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.

  18. 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.

  19. Foxp3 (-/ATT polymorphism contributes to the susceptibility of preeclampsia.

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    Ximing Chen

    Full Text Available OBJECTIVE: To evaluate the potential influence of Foxp3 polymorphism on preeclampsia (PE susceptibility, we conducted a case-control study in Han Chinese women. METHODS: Foxp3 genotyping was determined by polymerase chain reaction with sequence-specific primers (PCR-SSP in 156 PE patients and 252 age-frequency matched controls. Immunohistochemical staining was used to detect the expression of Foxp3 specific transcription factor in 30 PE and 30 normal pregnant women. RESULTS: The positive rate of Foxp3 expression in PE (26.67% was significant difference from that in normal control (63.33%, P<0.05. The frequency of Foxp3-6054 TT genotype was significantly lower in PE patient than that in control. No significant difference was found in Foxp3-3279 genotypes between PE and control, as well as for the variant allele. The frequency of Foxp3-6054A/-3279C haplotype in PE was significantly higher than that in control (P<0.01, while the frequency of Foxp3 6054T/-3279C haplotype was significantly lower in PE patient than that in control (P<0.01. CONCLUSION: Our findings suggest that the immune suppression function in PE patients is weakened, which may result in the occurrence of PE. Foxp3 polymorphism (rs5902434 may be a potential contributor for the development of PE in Han Chinese women.

  20. Social memory associated with estrogen receptor polymorphisms in women

    Science.gov (United States)

    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

  1. 2-(4-Fluorobenzylidenepropanedinitrile: monoclinic polymorph

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    Ahmed M. El-Agrody

    2013-04-01

    Full Text Available The title compound, C10H5FN2, is a monoclinic (P21/c polymorph of the previously reported triclinic (P-1 form [Antipin et al. (2003. J. Mol. Struct. 650, 1–20]. The 13 non-H atoms in the title polymorph are almost coplanar (r.m.s. deviation = 0.020 Å; a small twist between the fluorobenzene and dinitrile groups [C—C—C—C torsion angle = 175.49 (16°] is evident in the triclinic polymorph. In the crystal, C—H...N interactions lead to supramolecular layers parallel to (-101; these are connected by C—F...π interactions.

  2. Hapsembler: An Assembler for Highly Polymorphic Genomes

    Science.gov (United States)

    Donmez, Nilgun; Brudno, Michael

    As whole genome sequencing has become a routine biological experiment, algorithms for assembly of whole genome shotgun data has become a topic of extensive research, with a plethora of off-the-shelf methods that can reconstruct the genomes of many organisms. Simultaneously, several recently sequenced genomes exhibit very high polymorphism rates. For these organisms genome assembly remains a challenge as most assemblers are unable to handle highly divergent haplotypes in a single individual. In this paper we describe Hapsembler, an assembler for highly polymorphic genomes, which makes use of paired reads. Our experiments show that Hapsembler produces accurate and contiguous assemblies of highly polymorphic genomes, while performing on par with the leading tools on haploid genomes. Hapsembler is available for download at http://compbio.cs.toronto.edu/hapsembler.

  3. Investigation of drug polymorphism: Case of artemisinin

    International Nuclear Information System (INIS)

    Horosanskaia, E.; Seidel-Morgenstern, A.; Lorenz, H.

    2014-01-01

    Highlights: • The Artemisinin dimorphic system was found to be enantiotropic. • The Orthorhombic modification is the form stable at low-temperatures and the triclinic modification the form stable at high-temperatures. • The polymorphic phase transition occurs at ∼130 °C. - Abstract: The polymorphism of the anti-malarial compound artemisinin was examined. The phase behavior of solid artemisinin has experimentally been investigated using differential scanning calorimetry and temperature-resolved X-Ray powder diffraction. In addition, complementary solution studies and suspension experiments were performed. The results clearly confirm the existence of two modifications of artemisinin, which are related enantiotropically. The orthorhombic modification is the thermodynamically stable form at low temperatures, while the triclinic form is the stable one at higher temperatures with a transition temperature of ∼130 °C. Problems associated with analysis of the polymorphic phase behavior are comprehensively addressed

  4. Polymorphic trial in oxidative damage of arsenic exposed Vietnamese

    International Nuclear Information System (INIS)

    Fujihara, Junko; Soejima, Mikiko; Yasuda, Toshihiro; Koda, Yoshiro; Kunito, Takashi; Iwata, Hisato; Tanabe, Shinsuke; Takeshita, Haruo

    2011-01-01

    Arsenic causes DNA damage and changes the cellular capacity for DNA repair. Genes in the base excision repair (BER) pathway influence the generation and repair of oxidative lesions. Single nucleotide polymorphisms (SNPs) in human 8-oxoguanine DNA glycosylase (hOGG1) Ser326Cys; apurinic/apyrimidinic endonuclease (APE1) Asp148Glu; X-ray and repair and cross-complementing group 1 (XRCC1) Arg280His and Arg399Gln in the BER genes were analyzed, and the relationship between these 4 SNPs and the urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG) concentrations of 100 Vietnamese population exposed to arsenic was investigated. Individuals with hOGG1 326Cys/Cys showed significantly higher urinary 8-OHdG concentrations than did those with 326 Ser/Cys and Ser/Ser. As for APE1 Asp148Glu, heterozygous subjects showed significantly higher urinary 8-OHdG concentrations than did those homozygous for Asp/Asp. Moreover, global ethnic comparison of the allelic frequencies of the 4SNPs was performed in 10 population and previous reported data. The mutant allele frequencies of hOGG1 Ser326Cys in the Asian populations were higher than those in the African and Caucasian populations. As for APE1 Asp148Glu, Caucasians showed higher mutant frequencies than those shown by African and Asian populations. Among Asian populations, the Bangladeshi population showed relatively higher mutant allele frequencies of the APE1 Asp148Glu polymorphism. This study is the first to demonstrate the existence of genetic heterogeneity in a worldwide distribution of SNPs (hOGG1 Ser326Cys, APE1 Asp148Glu, XRCC1 Arg280His, and XRCC1 Arg399Gln) in the BER genes. - Highlights: → We showed that hOGG1 and APE1 are associated with urinary 8-OHdG concentrations. → We showed the existence of inter-ethnic differences in hOGG1 and APE1 polymorphism. → These polymorphisms is a genetic marker of susceptibility to oxidative stress.

  5. Polymorphisms in promoter sequences of MDM2, p53, and p16INK4a genes in normal Japanese individuals

    Directory of Open Access Journals (Sweden)

    Yasuhito Ohsaka

    2010-01-01

    Full Text Available Research has been conducted to identify sequence polymorphisms of gene promoter regions in patients and control subjects, including normal individuals, and to determine the influence of these polymorphisms on transcriptional regulation in cells that express wild-type or mutant p53. In this study we isolated genomic DNA from whole blood of healthy Japanese individuals and sequenced the promoter regions of the MDM2, p53, and p16INK4a genes. We identified polymorphisms comprising 3 nucleotide substitutions at exon 1 and intron 1 regions of the MDM2 gene and 1 nucleotide insertion at a poly(C nucleotide position in the p53 gene. The Japanese individuals also exhibited p16INK4a polymorphisms at several positions, including position -191. Reporter gene analysis by using luciferase revealed that the polymorphisms of MDM2, p53, and p16INK4a differentially altered luciferase activities in several cell lines, including the Colo320DM, U251, and T98G cell lines expressing mutant p53. Our results indicate that the promoter sequences of these genes differ among normal Japanese individuals and that polymorphisms can alter gene transcription activity.

  6. Polymorphic variants of neurotransmitter receptor genes may affect sexual function in aging males: data from the HALS study.

    Science.gov (United States)

    Jóźków, Paweł; Słowińska-Lisowska, Małgorzata; Łaczmański, Łukasz; Mędraś, Marek

    2013-01-01

    Human behavior is influenced by a number of brain neurotransmitters. Central dopamine, serotonin and melanocortin systems have special importance for male sexual function. We searched for associations between male aging symptoms and polymorphic sites of serotonin (5-HTR1B), melanocortin (MC4R) and dopamine (DRD2, DRD4) receptors. In a population-based sample, genotyping of 5-HTR1B (polymorphism: G861C), MC4R (polymorphisms: C-2745T, Val103Ile), DRD2 (polymorphism: C313T) and DRD4 (polymorphism: 48-bp VNTR) was performed in 387 healthy men. The Aging Males' Symptoms (AMS) scale was used to evaluate specific ailments of aging men. We analyzed answers to questions from the AMS scale. Five points of the questionnaire addressed sexual symptoms of the aging male: feeling of passing one's peak, decrease in beard growth, decrease in ability/frequency to perform sexually, decrease in the number of morning erections, and decrease in sexual desire/libido (lacking pleasure in sex, lacking desire for sexual intercourse). Relations between reported symptoms and variants of the polymorphic sites of the studied genes were assessed. After adjusting for confounding factors (education, arterial hypertension, physical activity, weight, waist circumference) an association between the sexual dimension of AMS and genetic variants of 5-HTR1B G861C (p = 0.04) was observed. Variability of neurotransmitter receptor genes may be associated with sexual symptoms of aging in men. Copyright © 2013 S. Karger AG, Basel.

  7. Novel Association of WNK4 Gene, Ala589Ser Polymorphism in Essential Hypertension, and Type 2 Diabetes Mellitus in Malaysia

    Directory of Open Access Journals (Sweden)

    Nooshin Ghodsian

    2016-01-01

    Full Text Available With-no-lysine (K Kinase-4 (WNK4 consisted of unique serine and threonine protein kinases, genetically associated with an autosomal dominant form of hypertension. Argumentative consequences have lately arisen on the association of specific single nucleotide polymorphisms of WNK4 gene and essential hypertension (EHT. The aim of this study was to determine the association of Ala589Ser polymorphism of WNK4 gene with essential hypertensive patients in Malaysia. WNK4 gene polymorphism was specified utilizing mutagenically separated polymerase chain reaction (PCR and restriction fragment length polymorphism (RFLP method in 320 subjects including 163 cases and 157 controls. Close relation between Ala589Ser polymorphism and elevated systolic and diastolic blood pressure (SBP and DBP was recognized. Sociodemographic factors including body mass index (BMI, age, the level of fasting blood sugar (FBS, low density lipoprotein (LDL, and triglyceride (TG in the cases and healthy subjects exhibited strong differences (p<0.05. The distribution of allele frequency and genotype of WNK4 gene Ala589Ser polymorphism showed significant differences (p<0.05 between EHT subjects with or without type 2 diabetes mellitus (T2DM and normotensive subjects, statistically. The WNK4 gene variation influences significantly blood pressure increase. Ala589Ser probably has effects on the enzymic activity leading to enhanced predisposition to the disorder.

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

    Directory of Open Access Journals (Sweden)

    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.

  9. Impact of estrogen receptor α gene and oxytocin receptor gene polymorphisms on female sexuality

    Directory of Open Access Journals (Sweden)

    Anastasia K Armeni

    2017-02-01

    Full Text Available Over the past decades, research attention has increasingly been paid to the neurobiological component of sexual behavior. The aim of the present study was to investigate the correlation of estrogen receptor α (ERA gene polymorphism (rs2234693-PvuII (T→C substitution and oxytocin receptor gene polymorphism (rs53576 (G→A substitution with sexuality parameters of young, healthy women. One hundred thirty-three Greek heterosexual women, students in higher education institutions, 20–25 years of age, sexually active, with normal menstrual cycles (28–35 days, were recruited in the study. Exclusion criteria were chronic and/or major psychiatric diseases, use of oral contraceptive pills (OCs, polycystic ovary syndrome (PCOS, thyroid diseases as well as drugs that are implicated in hypothalamus–pituitary–gonadal axis. T allele (wildtype of rs2234693 (PvuII polymorphism of ERA gene was correlated with increased levels of arousal and lubrication, whereas A allele (polymorphic of rs53576 (OXTR polymorphism was correlated with increased arousal levels. The simultaneous presence of both T allele of rs2234693 (PvuII and A allele of rs53576 (OXTR polymorphisms (T + A group was correlated with increased arousal, orgasm levels as well as female sexual function index full score. To our knowledge, this is the first study to investigate the interaction between ERA and OXTR with regard to sexual function in women. Female sexuality is a complex behavioral trait that encompasses both biological and psychological components. It seems that variability in female sexual response stems from genetic variability that characterizes endocrine, neurotransmitter and central nervous system influences.

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

    Science.gov (United States)

    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

  11. Relationship of interleukin-1B gene promoter region polymorphism with Helicobacter pylori infection and gastritis.

    Science.gov (United States)

    Ramis, Ivy Bastos; Vianna, Júlia Silveira; Halicki, Priscila Cristina Bartolomeu; Lara, Caroline; Tadiotto, Thássia Fernanda; da Silva Maciel, João Batista; Gonçalves, Carla Vitola; von Groll, Andrea; Dellagostin, Odir Antônio; da Silva, Pedro Eduardo Almeida

    2015-09-29

    Helicobacter pylori infection is associated with gastritis, peptic ulcer disease and gastric carcinoma. The severity of damage is determined by the interplay between environmental/behavioral factors, bacterial pathogenicity genes and host genetic polymorphisms that can influence the secretion levels of inflammatory cytokines. Accordingly, this study aimed to identify polymorphisms in the IL-1B and IL-1RN genes and their associations with H. pylori infection, cagA gene of H. pylori, and gastroduodenal diseases. Gastric biopsy samples from 151 patients infected with H. pylori and 76 uninfected individuals were analyzed. H. pylori infection was diagnosed by histology and PCR. Polymorphisms at positions -511, -31 and +3954 of the IL-1B gene were detected by PCR-RFLP, and an analysis of the VNTR polymorphism of the IL-1RN gene was performed by PCR. It was observed that the presence of the T/T genotype at position -511 and the C/C genotype at position -31 were associated with H. pylori infection and with an increased risk of gastritis in H. pylori-positive patients. Additionally, strains from patients H. pylori-positive carrying the cagA gene was significantly related with the T/T genotype at position -511 of IL-1B.  No association of polymorphisms at position +3954 of IL-1B and in the IL-1RN with H. pylori infection and with risk of severe gastric diseases was found. We demonstrated that polymorphisms in the promoter region of the IL-1B gene (at positions -511 and -31) are associated with an enhanced risk of H. pylori infection as well as gastritis in H. pylori-positive patients.

  12. Interleukin gene polymorphisms in Chinese Han population with breast cancer, a case-control study.

    Science.gov (United States)

    Zuo, Xiaoxiao; Li, Miao; Yang, Ya; Liang, Tiansong; Yang, Hongyao; Zhao, Xinhan; Yang, Daoke

    2018-04-06

    Cytokines are known as important regulators of the cancer involved in inflammatory and immunological responses. This fact and plethora of gene polymorphism data prompted us to investigate IL1 gene polymorphisms in breast cancer (BC) patients. Totally, 530 patients with BC and 628 healthy control women were studied. The genetic polymorphisms for IL1 were analyzed by Massarray Sequencing method. Three single nucleotide polymorphisms (SNPs) identified in IL1B, IL1R1 gene are thought to influence breast cancer risk. The results of the association between IL-1B, IL1R1 polymorphisms and breast cancer risk have significant. We found that the variant TT genotype of rs10490571 was associated with a significantly increased breast cancer risk (TT vs. CC: OR = 2.82, 95% CI = 1.12-7.08, P = 0.047 for the codominant model). For rs16944 (AG vs. GG: OR = 0.60, 95% CI = 0.41-0.90, P = 0.034 for the codominant model) and rs1143623 (CG vs. CC: OR = 0.65, 95% CI = 0.45-0.94, P = 0.023 for the codominant model) have significant associations were found in genetic models. In conclusion, the present analysis suggests a correlation of polymorphic markers within the IL-1 gene locus with the risk in developing breast cancer. Taken together with our finding that IL1B, IL1R1 gene three SNP are also associated with the risk for the disease, we suggest that inflammation via innate and adaptive immunity contributes to multifactorial hereditary predisposition to pathogenesis of the breast cancer.

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

    Science.gov (United States)

    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).

  14. Association Between Promoter Polymorphisms in CD46 and CD59 in Kidney Donors and Transplant Outcome

    Directory of Open Access Journals (Sweden)

    Laura A. Michielsen

    2018-05-01

    Full Text Available Complement regulating proteins, including CD46, CD55, and CD59, protect cells against self-damage. Because of their expression on the donor endothelium, they are hypothesized to be involved in accommodation. Polymorphisms in their promoter regions may affect their expression. The aim of this study was to investigate if donor polymorphisms in complement regulating proteins influence kidney transplant outcomes. We included 306 kidney transplantations between 2005 and 2010. Five polymorphisms in the promoters of CD46, CD55, and CD59 were genotyped. A CD59 promoter polymorphism (rs147788946 in donors was associated with a lower 1-year rejection-free survival [adjusted hazard ratio (aHR 2.18, 95% CI 1.12–4.24] and a trend toward impaired 5-year graft survival (p = 0.08. Patients receiving a kidney with at least one G allele for the CD46 promoter polymorphism rs2796267 (A/G showed a lower rejection-free survival, though this became borderline significant after adjustment for potential confounders (aHR 1.87, 95% CI 0.96–3.65. A second CD46 promoter polymorphism (rs2796268, A/G, was also associated with a lower freedom from acute rejection in the presence of at least one G allele (aHR 1.95, 95% CI 1.03–3.68. Finally, the combined presence of both favorable genotypes of rs2796267 and rs147788946 had an additional protective effect both on acute rejection (p = 0.006 and graft survival (p = 0.03. These findings could help to identify patients who could benefit from intensified immunosuppressive therapy or novel complement inhibitory therapeutics.

  15. Polymorphic transformation of helical flagella of bacteria

    Science.gov (United States)

    Lim, Sookkyung; Howard Berg Collaboration; William Ko Collaboration; Yongsam Kim Collaboration; Wanho Lee Collaboration; Charles Peskin Collaboration

    2016-11-01

    Bacteria such as E. coli swim in an aqueous environment by utilizing the rotation of flagellar motors and alternate two modes of motility, runs and tumbles. Runs are steady forward swimming driven by bundles of flagellar filaments whose motors are turning CCW; tumbles involve a reorientation of the direction of swimming triggered by motor reversals. During tumbling, the helical flagellum undergoes polymorphic transformations, which is a local change in helical pitch, helical radius, and handedness. In this work, we investigate the underlying mechanism of structural conformation and how this polymorphic transition plays a role in bacterial swimming. National Science Foundation.

  16. The monoclinic polymorph of dimethylarsinic acid

    Directory of Open Access Journals (Sweden)

    Richard Betz

    2011-08-01

    Full Text Available The title compound, C2H7AsO2 or [As(CH32O(OH], is an organic derivative of arsinic acid, and is also known by its trivial name cacodylic acid. In contrast to the first polymorph (triclinic, space group Poverline{1}, Z = 2, the current study revealed monoclinic symmetry (space group C2/c, Z = 8 for the second polymorph. The configuration of the tetrahedral molecule shows approximate Cs symmetry. Strong O—H...O hydrogen bonds connect the molecules to infinite zigzag chains along [010], which are further connected by weak intermolecular C—H...O contacts into a three-dimensional network.

  17. 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...

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

    OpenAIRE

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

    2014-01-01

    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 (...

  19. Interaction of TLR-IFN and HLA polymorphisms on susceptibility of chronic HBV infection in Southwest Han Chinese.

    Science.gov (United States)

    He, Dengming; Tao, Shiqi; Guo, Shimin; Li, Maoshi; Wu, Junqiu; Huang, Hongfei; Guo, Xinwu; Yan, Guohua; Zhu, Peng; Wang, Yuming

    2015-08-01

    The toll-like receptor-interferon (TLR-IFN) signalling pathway plays a crucial role in HBV infection. Human leucocyte antigen (HLA) polymorphisms are associated with chronic HBV infection by genome wide association study (GWAS). We aimed to explore interaction between TLR-IFN and HLA gene polymorphisms in susceptibility of chronic HBV infection. In the Chinese Southwest Han population, 1191 chronic HBV infection patients and 273 HBV clearance were selected. A total of 39 single nucleotide polymorphism loci in 23 genes of the TLR-IFN pathway and four HLA polymorphism loci associated with chronic HBV infection identified by GWAS were selected for genotyping. SNPStats, QVALUE, and multifactor dimensionality reduction were used for statistical analysis. A significant association was seen in several of the TLR-IFN pathway genes, TLR9 rs352140 (OR = 0.70, P = 0.0088), IL1B rs16944 (OR = 0.67, P = 0.016), IL12B rs3212227 (OR = 1.38, P = 0.021), IFNGR1 rs3799488 (OR = 1.48, P = 0.0048), IFNGR2 rs1059293 (OR = 0.27, P = 0.011), MX1 rs467960 (OR = 0.68, P = 0.022), as well as four loci in HLA, rs3077 (OR = 0.55, P rs16944 (0.13%), rs1143623 and rs6613 (0.10%). The combination of rs9277535 in HLA and rs16944 in IL1B was the best model to predict chronic HBV infection (testing accuracy = 0.6040, P = 0.0010, cross-validation consistency = 10/10). TLR-IFN pathway gene polymorphisms are associated with chronic HBV infection. Interactions with polymorphisms in these genes may be one mechanism by which HLA polymorphisms influence susceptibility to chronic HBV infection, as specific single nucleotide polymorphism combinations are highly predictive of chronic HBV infection. © 2014 The Authors. Liver International Published by John Wiley & Sons Ltd.

  20. Polymorphism of the VEGF gene and its association with growth ...

    African Journals Online (AJOL)

    User

    Keywords: VEGF gene, caprine, single nucleotide polymorphism (SNP), genetic variation, PCR-SSCP ... This field is strongly focusing on gene loci and polymorphisms that have ..... Enhance the efficiency of single-strand conformation polymorphism analysis by short polyacrylamide gel and modified silver staining. Anal.

  1. Upper petal lip colour polymorphism in Collinsia heterophylla

    Indian Academy of Sciences (India)

    Understanding the genetics of a polymorphic trait is important to predict its likely evolution. In Collinsia heterophylla, the upper petal lip colour can be either be white or white with a purple band, while the lower petal lip colour is invariably purple. Because the corolla is only partly polymorphic, the polymorphism can not have ...

  2. The V279F polymorphism might change protein character and ...

    African Journals Online (AJOL)

    Polymorphisms at the protein level are also estimated to correlate with increased risk factors for heart attacks. One such polymorphism is the V279F polymorphism in Lp-PLA2 which results in a change in enzyme performance capability. This in turn implies a reduced risk of acute myocardial infarct (AMI) in Korean and ...

  3. Do prion protein gene polymorphisms induce apoptosis in non ...

    Indian Academy of Sciences (India)

    2016-08-26

    Aug 26, 2016 ... Genetic variations such as single nucleotide polymorphisms (SNPs) in prion protein coding gene, Prnp, greatly affect susceptibility to prion diseases in mammals. Here, the coding region of Prnp was screened for polymorphisms in redeared turtle, Trachemys scripta. Four polymorphisms, L203V, N205I, ...

  4. Relationship between human paraoxonase-1 activity and PON1 polymorphisms in Mexican workers exposed to organophosphate pesticides.

    Science.gov (United States)

    López-Flores, I; Lacasaña, M; Blanco-Muñoz, J; Aguilar-Garduño, C; Sanchez-Villegas, P; Pérez-Méndez, O A; Gamboa-Avila, R

    2009-07-24

    Paraoxonase-1 (PON1) is a serum enzyme which catalyzes the hydrolysis of organophosphate pesticides. In this study we conducted a cross-sectional study and reported on the distribution of three common genetic polymorphisms of the PON1 gene in a population of floriculture workers from Mexico as well as the association between those polymorphisms and other predictors with serum PON1 activity on paraoxon, diazoxon and phenylacetate. The genotype frequencies at position PON1(55) were 89% (LL), 10% (LM) and 0.6% (MM), at position PON1(192) they were 16% (QQ), 47% (QR) and 37% (RR), and 26% (TT), 42% (TC) and 32% (CC) at position PON1(-108). Thus, the frequencies of alleles L, Q and T were 0.94, 0.40 and 0.47, respectively. The PON1(55) polymorphism had no significant effect on serum PON1 activity on any substrate. We found a significant association between the PON1(192) polymorphism and PON1 activity towards paraoxon and diazoxon, which increased in genotypes as follows: 192RR>192QR>192QQ for paraoxonase activity and, inversely, 192QQ>192QR>192RR for diazoxonase activity. The PON1(-108) polymorphism also had a significant effect on PON1 activity level towards paraoxon in the following order among the genotype groups: -108CC>-108TC>-108TT. Serum PON1 activity towards diazoxon was not associated with the PON1(-108) polymorphism but it was influenced by the intensity exposure to pesticides at the floriculture industry and the years of the occupational exposure to pesticides. No polymorphism significantly influenced serum PON1 activity on phenylacetate.

  5. Ascertainment bias in studies of human genome-wide polymorphism

    DEFF Research Database (Denmark)

    Clark, Andrew G.; Hubisz, Melissa J.; Bustamente, Carlos D.

    2005-01-01

    of the SNPs that are found are influenced by the discovery sampling effort. The International HapMap project relied on nearly any piece of information available to identify SNPs-including BAC end sequences, shotgun reads, and differences between public and private sequences-and even made use of chimpanzee...... was a resequencing-by-hybridization effort using the 24 people of diverse origin in the Polymorphism Discovery Resource. Here we take these two data sets and contrast two basic summary statistics, heterozygosity and FST, as well as the site frequency spectra, for 500-kb windows spanning the genome. The magnitude...... of disparity between these samples in these measures of variability indicates that population genetic analysis on the raw genotype data is ill advised. Given the knowledge of the discovery samples, we perform an ascertainment correction and show how the post-correction data are more consistent across...

  6. HAS-1 genetic polymorphism in sporadic abdominal aortic aneurysm

    Directory of Open Access Journals (Sweden)

    Alberto Balbarini

    2009-04-01

    Full Text Available The hyaluronan synthase 1 (HAS-1 gene encodes a plasma membrane protein that synthesizes hyaluronan (HA, an extracellular matrix molecule. Accumulating evidence emphasizes the relevance of HA metabolism in an increasing number of processes of clinical interest, including abdominal aortic aneurysm (AAA. The existence of aberrant splicing variants of the HAS-1 gene could partly explain the altered extracellular matrix architecture and influence various biological functions, resulting in progressive arterial wall failure in the development of AAA. In the present study, we assessed the hypothesis that HAS-1 genetic 833A/G polymorphism could be associated with the risk of AAA by performing a case-control association study, involving AAA patients and healthy matched donors.

  7. Diffuse scattering in metallic tin polymorphs

    International Nuclear Information System (INIS)

    Wehinger, Björn; Bosak, Alexeï; Piccolboni, Giuseppe; Krisch, Michael; Refson, Keith; Chernyshov, Dmitry; Ivanov, Alexandre; Rumiantsev, Alexander

    2014-01-01

    The lattice dynamics of the metallic tin β and γ polymorphs has been studied by a combination of diffuse scattering, inelastic x-ray scattering and density functional perturbation theory. The non-symmorphic space group of the β -tin structure results in unusual asymmetry of thermal diffuse scattering. Strong resemblance of the diffuse scattering intensity distribution in β and γ-tin were observed, reflecting the structural relationship between the two phases and revealing the qualitative similarity of the underlying electronic potential. The strong influence of the electron subsystem on inter-ionic interactions creates anomalies in the phonon dispersion relations. All observed features are described in great detail by the density functional perturbation theory for both β - and γ-tin at arbitrary momentum transfers. The combined approach delivers thus a complete picture of the lattice dynamics in harmonic description. (paper)

  8. Crystallization and transformation of polymorphic forms of trioleoyl glycerol and 1,2-dioleoyl-3-rac-linoleoyl glycerol.

    Science.gov (United States)

    Bayés-García, Laura; Calvet, Teresa; Cuevas-Diarte, Miquel Àngel; Ueno, Satoru; Sato, Kiyotaka

    2013-08-08

    This study examined the influence of different thermal treatments on the crystallization and transformation of trioleoyl glycerol (OOO) and 1,2-dioleoyl-3-rac-linoleoyl glycerol (OOL). Two triacylglycerol (TAG) samples were cooled at 0.5-15 °C·min(-1) and heated at 2 and 15 °C·min(-1). The polymorphic characteristics of the two TAGs were analyzed in situ using differential scanning calorimetry, Raman spectroscopy, and synchrotron radiation X-ray diffraction. Multiple polymorphic forms were identified in OOO (α, β'2, β'1, β2, and β1) and OOL (α, β'2, and β'1). Larger quantities of more stable forms (e.g., β2 and β1 of OOO and β'1 of OOL) were obtained when the samples were slowly cooled and heated. In contrast, less stable polymorphs were obtained with increased cooling and heating rates. Polymorphic transformations occurred in either solid-state or melt-mediation and were influenced by heating rates. The results were analyzed by considering the activation energies for crystallization and transformation of stable and less stable polymorphic forms in comparison with previous studies on 1,3-dipalmitoyl-2-oleoyl-glycerol and 1, 3-dioleoyl-2-palmitoyl-glycerol.

  9. Effect of GSTM1, GSTT1, and GSTP1 IIe105Val polymorphisms on susceptiblity to gestational diabetes mellitus.

    Science.gov (United States)

    Qiu, Y H; Xu, Y L; Zhang, W H

    2016-06-03

    We investigate the role of the GSTM1, GSTT1, and GSTP1 IIe105Val genetic polymorphisms in the susceptibility to gestational diabetes mellitus. A total of 223 pregnant women with gestational diabetes mellitus and 265 healthy pregnant women were examined at The Second Affiliated Hospital of Shaanxi University of Chinese Medicine from May 2013 to November 2013. Genotyping for detection of GSTM1, GSTT1, and GSTP1 IIe105Val polymorphisms was conducted using the restriction fragment length polymorphism-polymerase chain reaction. There were statistically significant differences between patients with gestational diabetes mellitus and control subjects in terms of age (χ(2) = 6.68, P = 0.01) and BMI (t = 7.56, P gestational diabetes mellitus compared to the present genotype [adjusted OR (95%CI) = 1.85 (1.26-2.72)]. However, the unconditional logistic analysis revealed that GSTT1 and GSTP1 IIe105Val polymorphisms could not influence the risk of gestational diabetes mellitus in a Chinese population. In summary, we suggest that the GSTM1 gene polymorphism could influence the susceptibility to gestational diabetes mellitus in a Chinese population.

  10. Polygenic influences on dyslipidemias.

    Science.gov (United States)

    Dron, Jacqueline S; Hegele, Robert A

    2018-04-01

    Rare large-effect genetic variants underlie monogenic dyslipidemias, whereas common small-effect genetic variants - single nucleotide polymorphisms (SNPs) - have modest influences on lipid traits. Over the past decade, these small-effect SNPs have been shown to cumulatively exert consistent effects on lipid phenotypes under a polygenic framework, which is the focus of this review. Several groups have reported polygenic risk scores assembled from lipid-associated SNPs, and have applied them to their respective phenotypes. For lipid traits in the normal population distribution, polygenic effects quantified by a score that integrates several common polymorphisms account for about 20-30% of genetic variation. Among individuals at the extremes of the distribution, that is, those with clinical dyslipidemia, the polygenic component includes both rare variants with large effects and common polymorphisms: depending on the trait, 20-50% of susceptibility can be accounted for by this assortment of genetic variants. Accounting for polygenic effects increases the numbers of dyslipidemic individuals who can be explained genetically, but a substantial proportion of susceptibility remains unexplained. Whether documenting the polygenic basis of dyslipidemia will affect outcomes in clinical trials or prospective observational studies remains to be determined.

  11. Polymorphism of a polymer precursor: metastable glycolide polymorph recovered via large scale high-pressure experiments

    DEFF Research Database (Denmark)

    Hutchison, Ian B.; Delori, Amit; Wang, Xiao

    2015-01-01

    Using a large volume high-pressure press a new polymorph of an important precursor for biomedical polymers was isolated in gram quantities and used to seed crystallisation experiments at ambient pressure....

  12. Association between the polymorphisms of angiotensin converting ...

    African Journals Online (AJOL)

    Detailed history taking was done with stress on age, family history, menstrual, obstetric, medical and drug history. Physical examination including body mass index calculation was done. Histopathological examination was done for tumor grading and staging. Detection of ACE gene (I/D) polymorphism by PCR and AT1R ...

  13. Methylenetetrahydrofolate Reductase C677T Polymorphism And ...

    African Journals Online (AJOL)

    reduction of 5, 10-methylenetetrahydrofolate to 5- methyltetrahydrofolate. A 677 C/T single nucleotide polymorphism (SNP) localized in the MTHFR gene was associated with both thermo ability and reduced activity of the enzyme and is associated with increased homocysteine levels. The aim of this study was to establish

  14. RESEARCH ARTICLE Analysis of polymorphisms and selective ...

    Indian Academy of Sciences (India)

    2017-01-27

    Jan 27, 2017 ... The presence of purifying selection and low nucleotide diversity indicated that ... protein in Plasmodium spp., and they are mainly due to single nucleotide polymorphisms (SNPs) ... This study was approved by Medical Research & Ethics Committee of the Ministry of. Health ..... X. Asembo Bay Cohort Project.

  15. Phenotypic characterisation and molecular polymorphism of ...

    African Journals Online (AJOL)

    The study of the phenotypic characterisation and molecular polymorphism of local chicken populations was carried out in Benin on 326 chickens of the Forest ecological area and 316 of the Savannah ecological area, all were 7 months old at least. The collection of blood for the molecular typing was achieved on 121 ...

  16. High-Pressure Polymorphism in Orthoamphiboles

    Science.gov (United States)

    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.

  17. Methylation sensitive amplified polymorphism (MSAP) reveals that ...

    African Journals Online (AJOL)

    ajl yemi

    2011-12-19

    Dec 19, 2011 ... Key words: Salt stress, alkali stress, Gossypium hirsutum L., DNA methylation, methylation sensitive amplified polymorphism (MSAP). INTRODUCTION. DNA methylation is one of the key epigenetic mecha- nisms among eukaryotes that can modulate gene expression without the changes of DNA sequence.

  18. Osteoprotegerin polymorphisms are associated with alcohol ...

    Indian Academy of Sciences (India)

    2016-12-02

    Dec 2, 2016 ... 4The College of Life Sciences, Northwest University, Xi'an, 710069, People's ... study is focussed on OPG gene polymorphisms associated with alcohol-induced ONFH. ... the risk of ONFH occurrence, and balanced on osteoclasts– ..... This work was supported by the National Natural Science Founda-.

  19. Association between Interleukin-18 promoter polymorphisms and ...

    African Journals Online (AJOL)

    Noha M. Bakr

    the study. Genotypic analysis of IL-18 promoter polymorphisms were performed using sequence- .... diabetes mellitus, heart disease, previous stroke, cigarette smok- ing. Included .... of the mutated AA genotype and A allele was observed in IS ..... factor for ischemic stroke in the Chinese population: a meta-analysis. Meta.

  20. Combined effect between two functional polymorphisms of ...

    Indian Academy of Sciences (India)

    four populations (Ireland, UK, Australia and Finland) reported an allelic association between ... of two common polymorphisms on SLC6A12 gene may be associated with TLE, but the ... Li L., Liu A., Wu X., Sun W., Wang Y. and Liu Y. 2015 Combined effect between two ... epileptic control subjects of Chinese Han origin were.

  1. MYO9B polymorphisms in multiple sclerosis

    DEFF Research Database (Denmark)

    Kemppinen, A.; Suvela, M.; Tienari, P.J.

    2009-01-01

    Single-nucleotide polymorphisms (SNPs) in the 3' region of myosin IXB (MYO9B) gene have recently been reported to associate with different inflammatory or autoimmune diseases. We monitored for the association of MYO9B variants to multiple sclerosis (MS) in four Northern European populations. First...

  2. Single-nucleotide polymorphisms in peroxisome proliferator ...

    Indian Academy of Sciences (India)

    However, association of these polymorphisms with the metabolic syndrome and its individual components has not been well investigated in the Indian population. The Indian population harbours the maximum number of diabetics in the world who are thus more susceptible to metabolic disorders. We screened a South ...

  3. Isolation and characterization of polymorphic microsatellite markers ...

    African Journals Online (AJOL)

    Flax (Linum usitatissimum L.) is the third largest natural fiber crop and one of the five major oil crops in the world. ... These novel polymorphic microsatellite loci will be useful in genetic linkage map construction, germplasm classification and identification, gene identification and QTL mapping, and marker-assisted selection ...

  4. OGG1 polymorphisms and breast cancer risk

    Czech Academy of Sciences Publication Activity Database

    Rössner ml., Pavel; Terry, M. B.; Gammon, M. D.; Zhang, F. F.; Teitelbaum, S. L.; Eng, S. M.; Sagiv, S. K.; Gaudet, M. M.; Neugut, A. I.; Santella, R. M.

    2006-01-01

    Roč. 15, č. 4 (2006), s. 811-815 ISSN 1055-9965 Institutional research plan: CEZ:AV0Z50390512 Keywords : genetic polymorphism * breast cancer Subject RIV: DN - Health Impact of the Environment Quality Impact factor: 4.289, year: 2006

  5. Difficulties in Learning Inheritance and Polymorphism

    Science.gov (United States)

    Liberman, Neomi; Beeri, Catriel; Kolikant, Yifat Ben-David

    2011-01-01

    This article reports on difficulties related to the concepts of inheritance and polymorphism, expressed by a group of 22 in-service CS teachers with an experience with the procedural paradigm, as they coped with a course on OOP. Our findings are based on the analysis of tests, questionnaires that the teachers completed in the course, as well as on…

  6. Koka: Programming with Row Polymorphic Effect Types

    Directory of Open Access Journals (Sweden)

    Daan Leijen

    2014-06-01

    Full Text Available We propose a programming model where effects are treated in a disciplined way, and where the potential side-effects of a function are apparent in its type signature. The type and effect of expressions can also be inferred automatically, and we describe a polymorphic type inference system based on Hindley-Milner style inference. A novel feature is that we support polymorphic effects through row-polymorphism using duplicate labels. Moreover, we show that our effects are not just syntactic labels but have a deep semantic connection to the program. For example, if an expression can be typed without an _exn_ effect, then it will never throw an unhandled exception. Similar to Haskell's `runST` we show how we can safely encapsulate stateful operations. Through the state effect, we can also safely combine state with let-polymorphism without needing either imperative type variables or a syntactic value restriction. Finally, our system is implemented fully in a new language called Koka and has been used successfully on various small to medium-sized sample programs ranging from a Markdown processor to a tier-splitted chat application. You can try out Koka live at www.rise4fun.com/koka/tutorial.

  7. LIG1 polymorphisms: the Indian scenario

    Indian Academy of Sciences (India)

    Elucidation of the genetic diversity and relatedness of the subpopulations of India may provide a unique resource for future analysis of genetic association of several critical community-specific complex diseases.We performed a comprehensive exploration of single nucleotide polymorphisms (SNPs) within the gene DNA ...

  8. Formation of Piroxicam Polymorphism in Solution Crystallization

    DEFF Research Database (Denmark)

    Bruun Hansen, Thomas; Qu, Haiyan

    2015-01-01

    also explored, and new insights into polymorphic control are documented and discussed. The crystal landscape was mapped for cooling crystallization of piroxicam from acetone/water mixtures (0.5 K/min) and for antisolvent crystallization from acetone with water as the antisolvent. Varying cooling rates...

  9. Endothelial nitric oxide synthase gene polymorphisms associated ...

    African Journals Online (AJOL)

    Endothelial nitric oxide synthase (NOS3) is involved in key steps of immune response. Genetic factors predispose individuals to periodontal disease. This study's aim was to explore the association between NOS3 gene polymorphisms and clinical parameters in patients with periodontal disease. Genomic DNA was obtained ...

  10. Random amplified polymorphic DNA based genetic characterization ...

    African Journals Online (AJOL)

    Random amplified polymorphic DNA based genetic characterization of four important species of Bamboo, found in Raigad district, Maharashtra State, India. ... Bambusoideae are differentiated from other members of the family by the presence of petiolate blades with parallel venation and stamens are three, four, six or more, ...

  11. Extended Polymorphism of Two-Dimensional Material

    NARCIS (Netherlands)

    Yoshida, Masaro; Ye, Jianting; Zhang, Yijin; Imai, Yasuhiko; Kimura, Shigeru; Fujiwara, Akihiko; Nishizaki, Terukazu; Kobayashi, Norio; Nakano, Masaki; Iwasa, Yoshihiro

    When controlling electronic properties of bulk materials, we usually assume that the basic crystal structure is fixed. However, in two-dimensional (2D) materials, atomic structure or to functionalize their properties. Various polymorphs can exist in transition metal dichalcogenides (TMDCs) from

  12. Mitochondrial mutations and polymorphisms in psychiatric disorders

    NARCIS (Netherlands)

    V. Sequeira (Vasco); M.V. Martin (Maureen); S.M. Rollins; E.A. Moon (Emily); W.E. Bunney (William E); F. MacCiardi (Fabio); S. Lupoli (Sara); G.D. Smith; J. Kelsoe (John); C.N. Magnan (Christophe); M. van Oven (Mannis); P. Baldi (Pierre); D.C. Wallace; M.P. Vawter (Marquis)

    2012-01-01

    textabstractMitochondrial deficiencies with unknown causes have been observed in schizophrenia (SZ) and bipolar disorder (BD) in imaging and postmortem studies. Polymorphisms and somatic mutations in mitochondrial DNA (mtDNA) were investigated as potential causes with next generation sequencing of

  13. Impact of polymorphisms in the HCP5 and HLA-C, and ZNRD1 genes on HIV viral load

    DEFF Research Database (Denmark)

    Thørner, Lise Wegner; Erikstrup, Christian; Harritshøj, Lene Holm

    2016-01-01

    AIMS: Single nucleotide polymorphisms (SNPs) in the human leucocyte antigen (HLA) complex P5 (HCP5), HLA-C, and near the zinc ribbon domain containing 1 (ZNRD1) have been shown to influence viral load (VL) set point in HIV-infected individuals with a known seroconversion onset. We aimed to determ...

  14. Renin-angiotensin system inhibitors, angiotensin I-converting enzyme gene insertion/deletion polymorphism, and cancer: The Rotterdam study

    NARCIS (Netherlands)

    R. van der Knaap (Ronald); C. Siemes (Claire); J.W.W. Coebergh (Jan Willem); P. Tikka-Kleemola (Päivi); A. Hofman (Albert); B.H.Ch. Stricker (Bruno)

    2008-01-01

    textabstractBACKGROUND. Angiotensin I-converting enzyme (ACE) inhibitors, angiotensin II antagonists, and the ACE insertion/deletion (I/D) gene polymorphism all influence serum angiotensin II action. Because angiotensin II levels have been associated with cancer, the objective of the current

  15. Mannose-binding lectin (MBL2) and ficolin-2 (FCN2) polymorphisms in patients on peritoneal dialysis with staphylococcal peritonitis

    NARCIS (Netherlands)

    Meijvis, Sabine C. A.; Herpers, Bjorn L.; Endeman, Henrik; de Jong, Ben; van Hannen, Erik; van Velzen-Blad, Heleen; Krediet, Raymond T.; Struijk, Dirk G.; Biesma, Douwe H.; Bos, Willem Jan W.

    Background. Mannose-binding lectin (MBL) and ficolin-2 (FCN) are activators of the lectin pathway of complement and act as primary defences against infection. Single-nucleotide polymorphisms (SNPs) in the MBL2 and FCN2 genes influence the functionality of the proteins. Both proteins are capable of

  16. Genetic Polymorphisms in Cytokine Genes in Colombian Patients with Ocular Toxoplasmosis.

    Science.gov (United States)

    Naranjo-Galvis, C A; de-la-Torre, A; Mantilla-Muriel, L E; Beltrán-Angarita, L; Elcoroaristizabal-Martín, X; McLeod, R; Alliey-Rodriguez, N; Begeman, I J; López de Mesa, C; Gómez-Marín, J E; Sepúlveda-Arias, J C

    2018-04-01

    Toxoplasmosis is caused by infection with the protozoan parasite Toxoplasma gondii , which has the capacity to infect all warm-blooded animals worldwide. Toxoplasmosis is a major cause of visual defects in the Colombian population; however, the association between genetic polymorphisms in cytokine genes and susceptibility to ocular toxoplasmosis has not been studied in this population. This work evaluates the associations between polymorphisms in genes coding for the cytokines tumor necrosis factor alpha (TNF-α) (rs1799964, rs1800629, rs1799724, rs1800630, and rs361525), interleukin 1β (IL-1β) (rs16944, rs1143634, and rs1143627), IL-1α (rs1800587), gamma interferon (IFN-γ) (rs2430561), and IL-10 (rs1800896 and rs1800871) and the presence of ocular toxoplasmosis (OT) in a sample of a Colombian population (61 patients with OT and 116 healthy controls). Genotyping was performed with the "dideoxynucleotide (ddNTP) primer extension" technique. Functional-effect predictions of single nucleotide polymorphisms (SNPs) were done by using FuncPred. A polymorphism in the IL-10 gene promoter (-1082G/A) was significantly more prevalent in OT patients than in controls ( P = 1.93e-08; odds ratio [OR] = 5.27e+03; 95% confidence interval [CI] = 3.18 to 8.739; Bonferroni correction [BONF] = 3.48e-07). In contrast, haplotype "AG" of the IL-10 gene promoter polymorphisms (rs1800896 and rs1800871) was present at a lower frequency in OT patients ( P = 7e-04; OR = 0.10; 95% CI = 0.03 to 0.35). The +874A/T polymorphism of IFN-γ was associated with OT ( P = 3.37e-05; OR = 4.2; 95% CI = 2.478 to 7.12; BONF = 6.07e-04). Haplotype "GAG" of the IL-1β gene promoter polymorphisms (rs1143634, rs1143627, and rs16944) appeared to be significantly associated with OT ( P = 0.0494). The IL-10, IFN-γ, and IL-1β polymorphisms influence the development of OT in the Colombian population. Copyright © 2018 American Society for Microbiology.

  17. Powder X-ray diffraction studies of structural and kinetic aspects of polymorphism

    International Nuclear Information System (INIS)

    Chan, F.C.

    1999-01-01

    Polymorphism is a poorly understood phenomenon that is of considerable technological interest to the pharmaceutical industry. The polymorph selected can influence the bioavailability, processing and stability of the pharmaceutical dosage form. In this study structural, kinetic and thermodynamics aspects of polymorphism and polymorphic phase transformations have been examined using powder X-ray diffraction (PXRD). The compound sulphathiazole is a well-studied model in the investigation of polymorphism and crystal growth. There are five known polymorphic forms and the structure of form V was unknown until this study. The difficulty has been that it has not been possibly to prepare crystals of appropriate size and quality for single crystal diffraction. Furthermore, structure solution from powder data for organic molecules is almost impossible. Despite the challenge the structure of sulphathiazole form V have been solved ab initio from powder data using direct methods. With 16 non-hydrogen atoms in the molecule and two molecules in the asymmetric unit, this structure represents a significant advance in terms of the complexity of an organic structure solved from PXRD data. The structural data should be invaluable for rationalizing experimental observations and the development of theoretical ideas regarding polymorphism and crystal growth. The second part of the study, has examined kinetics of polymorphic phase transformations as a function of pressure combined with temperature using real-time synchrotron PXRD. The significance of pressure arises from the fact that phase transitions can be induced in pharmaceuticals during tabletting. The phase transformation behaviour of rubidium iodide (chosen as a simple test model) has been investigated as a function of isobaric pressure at ambient and elevated temperatures. The kinetics have been characterized by using the Johnson-Melil-Avrami equation. The effect of successive cycling across the transition pressure was also

  18. The Polymorphism of Pituitary Factor 1 (POU1F1 in Cattle

    Directory of Open Access Journals (Sweden)

    Teodora Crina Carsai

    2012-05-01

    Full Text Available The development and function of mammary gland is mainly controlled by growth hormone and prolactin, twoprotein hormones secreted by the anterior pituitary gland. Their synthesis is under regulatory influence of pituitaryfactor 1 (PIT1 or POU1F1, a protein factor produced in hypothalamic nuclei. In cattle, it was shown that a HinfIpolymorphism located in exon 6 of PIT1 gene may have significant influence on milk quantity. In particular A allelewas associated with a higher milk yield and could be a valuable genetic marker for improving milk quantity in cattle.In an effort to better understand the possible influence of this polymorphism on mammary gland development andfunction in cattle, we have studied the frequency this polymorphism in Romanian Black and White breed, a highmilk production cattle breed versus Romanian Grey Steppe breed, a primitive breed with very low milk production.In both breeds the frequency of B allele is much higher as compared with the frequency of A allele. The study ofPIT1 polymorphism in Romanian cattle breeds is a part of a more complex study targeting several key genesinvolved in mammary gland function.

  19. Polymorphisms in the ghrelin gene and their associations with milk yield and quality in water buffaloes.

    Science.gov (United States)

    Gil, F M M; de Camargo, G M F; Pablos de Souza, F R; Cardoso, D F; Fonseca, P D S; Zetouni, L; Braz, C U; Aspilcueta-Borquis, R R; Tonhati, H

    2013-05-01

    Ghrelin is a gastrointestinal hormone that acts in releasing growth hormone and influences the body general metabolism. It has been proposed as a candidate gene for traits such as growth, carcass quality, and milk production of livestock because it influences feed intake. In this context, the aim of this study was to verify the existence of polymorphisms in the ghrelin gene and their associations with milk, fat and protein yield, and percentage in water buffaloes (Bubalus bubalis). A group of 240 animals was studied. Five primer pairs were used and 11 single nucleotide polymorphisms (SNP) were found in the ghrelin gene by sequencing. The animals were genotyped for 8 SNP by PCR-RFLP. The SNP g.960G>A and g.778C>T were associated with fat yield and the SNP g.905T>C was associated with fat yield and percentage and protein percentage. These SNP are located in intronic regions of DNA and may be in noncoding RNA sites or affect transcriptional efciency. The ghrelin gene in buffaloes influences milk fat and protein synthesis. The polymorphisms observed can be used as molecular markers to assist selection. Copyright © 2013 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

  20. Effects of BDNF polymorphisms on antidepressant action.

    Science.gov (United States)

    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

  1. 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.

  2. Association of LPP and TAGAP Polymorphisms with Celiac Disease Risk: A Meta-Analysis

    Directory of Open Access Journals (Sweden)

    Shi-Qi Huang

    2017-02-01

    Full Text Available Background: Lipoma preferred partner (LPP and T-cell activation Rho GTPase activating protein (TAGAP polymorphisms might influence the susceptibility to celiac disease. Therefore, we performed a meta-analysis by identifying relevant studies to estimate the risks of these polymorphisms on celiac disease. Methods: The PubMed, Web of Science and Embase databases were searched (up to October 2016 for LPP rs1464510 and TAGAP rs1738074 polymorphisms. Results: This meta-analysis included the same 7 studies for LPP rs1464510 and TAGAP rs1738074. The minor risk A allele at both rs1464510 and rs1738074 carried risks (odds ratios of 1.26 (95% CI: 1.22–1.30 and 1.17 (95% CI: 1.14–1.21, respectively, which contributed to increased risks in all celiac disease patients by 10.72% and 6.59%, respectively. The estimated lambdas were 0.512 and 0.496, respectively, suggesting that a co-dominant model would be suitable for both gene effects. Conclusions: This meta-analysis provides robust estimates that polymorphisms in LPP and TAGAP genes are potential risk factors for celiac disease in European and American. Prospective studies and more genome-wide association studies (GWAS are needed to confirm these findings, and some corresponding molecular biology experiments should be carried out to clarify the pathogenic mechanisms of celiac disease.

  3. Ecosensitivity and genetic polymorphism of somatic traits in the perinatal development of twins.

    Science.gov (United States)

    Waszak, Małgorzata; Cieślik, Krystyna; Skrzypczak-Zielińska, Marzena; Szalata, Marlena; Wielgus, Karolina; Kempiak, Joanna; Bręborowicz, Grzegorz; Słomski, Ryszard

    2016-04-01

    In view of criticism regarding the usefulness of heritability coefficients, the aim of this study was to analyze separately the information on genetic and environmental variability. Such an approach, based on the normalization of trait's variability for its value, is determined by the coefficients of genetic polymorphism (Pg) and ecosensitivity (De). The studied material included 1263 twin pairs of both sexes (among them 424 pairs of monozygotic twins and 839 pairs of dizygotic twins) born between the 22nd and 41st week of gestation. Variability of six somatic traits was analyzed. The zygosity of same-sex twins was determined based on the polymorphism of DNA from lymphocytes of the umbilical cord blood, obtained at birth. The coefficients of genetic polymorphism and ecosensitivity for analyzed traits of male and female twins born at various months of gestation were calculated. Our study revealed that a contribution of the genetic component predominated over that of the environmental component in determining the phenotypic variability of somatic traits of newborns from twin pregnancies. The genetically determined phenotypic variability in male twins was greater than in the females. The genetic polymorphism and ecosensitivity of somatic traits were relatively stable during the period of fetal ontogeny analyzed in this study. Only in the case of body weight, a slight increase in the genetic contribution of polygenes to the phenotypic variance could be observed with gestational age, along with a slight decrease in the influence of environmental factors. Copyright © 2015 Elsevier GmbH. All rights reserved.

  4. The association of ACE gene polymorphism with diabetic kidney disease and renoprotective efficacy of valsartan

    Directory of Open Access Journals (Sweden)

    Yuying Wang

    2016-09-01

    Full Text Available Introduction: To investigate the associations between the insertion/deletion (I/D polymorphisms in the angiotensin converting enzyme (ACE gene and susceptibility to diabetic kidney disease (DKD; and the efficacy of valsartan in reducing the urine protein in Type 2 diabetes mellitus (T2DM patients. Materials and methods: We enrolled 128 T2DM patients in this study, including 54 cases with DKD (DKD+ and 74 controls (DKD–. The ACE polymorphism was assayed by polymerase chain reaction (PCR, and the genotype distribution and allele frequency were analyzed. The DKD+ group was subdivided into the DD, ID and II subgroups, based on their genotypes. In addition, patients with DKD received valsartan treatment for 12 weeks. We determined changes in the urinary albumin to creatinine ratio (ACR and serum creatinine (SCr. Results: The frequencies of the genotypes DD and ID were higher in the DKD+ than in the DKD– group. The frequency of allele D was higher, and of allele I was lower, in the DKD+ than in DKD– group (p < 0.05. Following valsartan treatment, albuminuria was significantly decreased in subgroups DD and ID (p < 0.05. Conclusions: In T2DM patients, the ACE I/D polymorphism was associated with onset of DKD. Furthermore, the ACE I/D polymorphism influenced the renoprotective response to valsartan: Patients with the DD genotype benefitted the most from this treatment.

  5. The association of ACE gene polymorphism with diabetic kidney disease and renoprotective efficacy of valsartan.

    Science.gov (United States)

    Wang, Yuying; Peng, Wen; Zhang, Xiaoxue; Qiao, Huibo; Wang, Li; Xu, Zhigang; Wu, Chenguang

    2016-07-01

    To investigate the associations between the insertion/deletion (I/D) polymorphisms in the angiotensin converting enzyme (ACE) gene and susceptibility to diabetic kidney disease (DKD); and the efficacy of valsartan in reducing the urine protein in Type 2 diabetes mellitus (T2DM) patients. We enrolled 128 T2DM patients in this study, including 54 cases with DKD (DKD+) and 74 controls (DKD-). The ACE polymorphism was assayed by polymerase chain reaction (PCR), and the genotype distribution and allele frequency were analyzed. The DKD+ group was subdivided into the DD, ID and II subgroups, based on their genotypes. In addition, patients with DKD received valsartan treatment for 12 weeks. We determined changes in the urinary albumin to creatinine ratio (ACR) and serum creatinine (SCr). The frequencies of the genotypes DD and ID were higher in the DKD+ than in the DKD- group. The frequency of allele D was higher, and of allele I was lower, in the DKD+ than in DKD- group (p ACE I/D polymorphism was associated with onset of DKD. Furthermore, the ACE I/D polymorphism influenced the renoprotective response to valsartan: Patients with the DD genotype benefitted the most from this treatment. © The Author(s) 2016.

  6. Assessment of TNFA polymorphisms at positions -857 and -863 in Polish peptic ulcer patients.

    Science.gov (United States)

    Sałagacka-Kubiak, Aleksandra; Zebrowska, Marta; Jeleń, Agnieszka; Mirowski, Marek; Balcerczak, Ewa

    2016-03-01

    Peptic ulceration connected with chronic inflammation in gastrointestinal mucosa could be induced by Helicobacter pylori infection. Tumor necrosis factor alpha (TNF-α) encoded by TNFA gene is a key mediator in the inflammation process. There are several polymorphisms in the promoter of TNFA influencing its transcriptional activity. -857C>T (rs1799724) and -863C>A (rs1800630) substitutions may be responsible for increased TNFA transcription and TNF-α production. The association of these two polymorphisms with peptic ulceration and the development of H. pylori infection in peptic ulcer patients in Poles were evaluated. Polymorphisms were assessed by PCR-RFLP in 203 peptic ulcer patients. H. pylori infection was confirmed by rapid urease test. The results of genotyping were compared with those obtained for 248 healthy Polish individuals. There were no significant differences in genotype and allele frequencies for both investigated polymorphisms between peptic ulcer patients and healthy individuals. No associations between frequencies of particular genotypes and alleles for both SNPs and the presence of H. pylori infection in peptic ulcer patients and in subgroups of peptic ulcer women and men were confirmed. The investigated SNPs are not risk factors for peptic ulcer development. They are not risk factors for H. pylori infection in ulcer patients. Copyright © 2015 Medical University of Bialystok. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

  7. Sleep quality and OPRM1 polymorphisms: a cross-sectional study among opioid-naive individuals

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    Zalina Zahari

    2018-06-01

    Full Text Available ABSTRACT Opioidergic system involves in regulation of sleep and wakefulness. It is possible, therefore, that genetic polymorphisms in OPRM1 influence sleep quality. This study investigated the association of OPRM1 polymorphisms with subjective sleep quality among opioid-naive individuals. This cross-sectional observational study involved 161 opioid-naive males (mean age = 27.74 years; range: 18−63 years. Subjective sleep quality was assessed with the translated and validated Malay version of the Pittsburgh Sleep Quality Index (PSQI. DNA was extracted from whole blood and subjected to polymerase chain reaction (PCR-genotyping for two OPRM1 polymorphisms (118A>G and IVS2+691G>C. Subjects with combined 118A and IVS2+691G alleles (AC haplotype had significantly lower PSQI scores [mean (SD = 4.29 (1.76] compared to those without the haplotype [4.99 (2.50] (p = 0.004. On the other hand, subjects with combined heterozygous genotype (GC/AG diplotype had significantly higher PSQI scores compared to those without the diplotype [6.04 (2.48 vs 4.54 (2.22, p = 0.004]. In opioid-naive individuals, AC haplotype and GC/AG diplotype for the 118A>G and IVS2+691G>C polymorphisms of OPRM1 are associated with better and poorer sleep quality, respectively.

  8. Relationship between major depressive disorder and ACE gene I/D polymorphism in a Turkish population

    Directory of Open Access Journals (Sweden)

    Sema Inanir

    2016-04-01

    Full Text Available Abstract Background Major depressive disorder (MDD is a complex disease and a significant health problem that is prevalent across the world. Angiotensin-converting enzyme (ACE has an important role in renin-angiotensin system (RAS and converts inactive angiotensin I to a potent vasopressor and aldosterone-stimulating peptide angiotensin II. Levels of ACE in plasma vary according to the insertion/deletion (I/D polymorphism of ACE gene. Objective The aim of the current study was to examine the influence ACE gene I/D variations on the risk of MDD. Methods In the present case-control study, we analyzed ACE I/D polymorphism in 346 MDD patients and 210 healthy subjects using polymerase chain reaction technique. Results Comparing the two groups, no significant difference was observed with regard to either genotype distributions or allele frequencies of the I/D polymorphism of ACE gene. Discussion Our findings suggest that the ACE I/D polymorphism is not associated with MDD in Turkish case-control study. Further studies are still needed.

  9. Polymorphic Behavior and Phase Transition of Poly(1-Butene and Its Copolymers

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    Rui Xin

    2018-05-01

    Full Text Available The properties of semicrystalline polymeric materials depend remarkably on their structures, especially for those exhibiting a polymorphic behavior. This offers an efficient way to tailor their properties through crystal engineering. For control of the crystal structure, and therefore the physical and mechanical properties, a full understanding of the polymorph selection of polymers under varied conditions is essential. This has stimulated a mass of research work on the polymorphic crystallization and related phase transformation. Considering that the isotactic poly(1-butene (iPBu exhibits pronounced polymorphs and complicated transition between different phases, the study on its crystallization and phase transformation has attracted considerable attention during the past decades. This review provides the context of the recent progresses made on the crystallization and phase transition behavior of iPBu. We first review the crystal structures of known crystal forms and then their formation conditions and influencing factors. In addition, the inevitable form II to form I spontaneous transition mechanism and the transformation kinetics is reviewed based on the existing research works, aiming for it to be useful for its processing in different phases and the further technical development of new methods for accelerating or even bypass its form II to form I transformation.

  10. Association study between BDNF C-281A polymorphism and paranoid schizophrenia in Polish population.

    Science.gov (United States)

    Suchanek, Renata; Owczarek, Aleksander; Kowalski, Jan

    2012-01-01

    Brain-derived neurotrophic factor (BDNF) is one of the candidate genes for schizophrenia. Polymorphism C-281A (rs28383487) in BDNF gene leads to the reduction of promoter activity in the hippocampal neurons in vitro. To our knowledge, this is the first study to examine the influence of alleles and genotypes of BDNF C-281A polymorphism on development, as well as the clinical course (age of onset, suicidal behaviour and psychopathology) of paranoid schizophrenia. The psychopathology was assessed using the Positive and Negative Syndrome Scale (PANSS) as subscale scores and also single-item scores. We have also performed the haplotype analysis with val66met BDNF polymorphism, which is known to be involved in the pathogenesis of schizophrenia. We have not found significant differences in the distribution of genotypes and alleles between schizophrenic patients and controls in both the overall analysis, as well as sex stratified. Also, we have not shown statistically significant differences between genotype groups and PANSS scale. However, an association between C-281A polymorphism and time of the first episode of paranoid schizophrenia was revealed. Genotype C/A had been connected with later age of onset of paranoid schizophrenia in men but not in women (p schizophrenia group compared to the controls.

  11. Cytokine single-nucleotide polymorphisms and risk of non-small-cell lung cancer.

    Science.gov (United States)

    Pérez-Ramírez, Cristina; Alnatsha, Ahmed; Cañadas-Garre, Marisa; Villar, Eduardo; Valdivia-Bautista, Javier; Faus-Dáder, María J; Calleja-Hernández, Miguel Á

    2017-12-01

    Lung cancer, particularly the non-small-cell lung cancer (NSCLC) subtype, is the leading cause of cancer-related death worldwide. Several functional polymorphisms in inflammatory cytokine genes, such as IL1B, IL6, IL12A, IL13 and IL16, have been associated with the risk of NSCLC. The aim of this study was to evaluate the association between ILs gene polymorphisms and the risk of developing NSCLC. A retrospective case-control study was carried out, including 174 NSCLC cases and 298 controls of Spanish origin. IL1B (rs1143634), IL1B (rs12621220), IL1B (rs1143623), IL1B (rs16944), IL1B (rs1143627), IL12A (rs662959), IL13 (rs1881457), IL6 (rs1800795) and IL16 (rs7170924) gene polymorphisms were analysed by TaqMan. The genotypic logistic regression model adjusted by smoking status showed that the IL1B rs1143634-TT genotype was associated with a lower risk of NSCLC (P=0.04312; odds ratio=0.226; 95% confidence interval=0.044-0.840). No other gene polymorphisms showed an association with NSCLC in any of the models tested. In conclusion, IL1B rs1143634 was significantly associated with a higher risk of NSCLC. No influence of IL1B rs12621220, rs1143623, rs16944, rs1143627, IL12A rs662959, IL13 rs1881457 and IL16 rs7170924 on the risk of developing NSCLC was found in our study.

  12. Association between presenilin-1 polymorphism and maternal meiosis II errors in Down syndrome.

    Science.gov (United States)

    Petersen, M B; Karadima, G; Samaritaki, M; Avramopoulos, D; Vassilopoulos, D; Mikkelsen, M

    2000-08-28

    Several lines of evidence suggest a shared genetic susceptibility to Down syndrome (DS) and Alzheimer disease (AD). Rare forms of autosomal-dominant AD are caused by mutations in the APP and presenilin genes (PS-1 and PS-2). The presenilin proteins have been localized to the nuclear membrane, kinetochores, and centrosomes, suggesting a function in chromosome segregation. A genetic association between a polymorphism in intron 8 of the PS-1 gene and AD has been described in some series, and an increased risk of AD has been reported in mothers of DS probands. We therefore studied 168 probands with free trisomy 21 of known parental and meiotic origin and their parents from a population-based material, by analyzing the intron 8 polymorphism in the PS-1 gene. An increased frequency of allele 1 in mothers with a meiosis II error (70.8%) was found compared with mothers with a meiosis I error (52.7%, P < 0.01), with an excess of the 11 genotype in the meiosis II mothers. The frequency of allele 1 in mothers carrying apolipoprotein E (APOE) epsilon4 allele (68.0%) was higher than in mothers without epsilon4 (52.2%, P < 0.01). We hypothesize that the PS-1 intronic polymorphism might be involved in chromosomal nondisjunction through an influence on the expression level of PS-1 or due to linkage disequilibrium with biologically relevant polymorphisms in or outside the PS-1 gene. Copyright 2000 Wiley-Liss, Inc.

  13. Why to synthesize vaterite polymorph of calcium carbonate on the cellulose matrix via sonochemistry process?

    Science.gov (United States)

    Fu, Lian-Hua; Dong, Yan-Yan; Ma, Ming-Guo; Yue, Wen; Sun, Shao-Long; Sun, Run-Cang

    2013-09-01

    Vaterite is an important biomedical material due to its features such as high specific surface area, high solubility, high dispersion, and small specific gravity. The purposes of this article were to explore the growth mechanism of vaterite on the cellulose matrix via sonochmistry process. In the work reported herein, the influences of experimental parameters on the polymorph of calcium carbonate were investigated in detail. The calcium carbonate crystals on the cellulose matrix were characterized by means of X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), and scanning electron microscopy (SEM). Experimental results revealed that all the reactants, solvent, and synthesis method played an important role in the polymorph of calcium carbonate. The pure phase of vaterite polymorph was obtained using Na2CO3 as reactant in ethylene glycol on the cellulose matrix via sonochmistry process. Based on the experimental results, one can conclude that the synthesis of vaterite polymorph is a system process. Copyright © 2013 Elsevier B.V. All rights reserved.

  14. Association of STAT4 polymorphisms with susceptibility to type-1 autoimmune hepatitis in the Japanese population.

    Science.gov (United States)

    Migita, Kiyoshi; Nakamura, Minoru; Abiru, Seigo; Jiuchi, Yuka; Nagaoka, Shinya; Komori, Atsumasa; Hashimoto, Satoru; Bekki, Shigemune; Yamasaki, Kazumi; Komatsu, Tatsuji; Shimada, Masaaki; Kouno, Hiroshi; Hijioka, Taizo; Kohjima, Motoyuki; Nakamuta, Makoto; Kato, Michio; Yoshizawa, Kaname; Ohta, Hajime; Nakamura, Yoko; Takezaki, Eiichi; Nishimura, Hideo; Sato, Takeaki; Ario, Keisuke; Hirashima, Noboru; Oohara, Yukio; Naganuma, Atsushi; Muro, Toyokichi; Sakai, Hironori; Mita, Eiji; Sugi, Kazuhiro; Yamashita, Haruhiro; Makita, Fujio; Yatsuhashi, Hiroshi; Ishibashi, Hiromi; Yasunami, Michio

    2013-01-01

    Recent studies demonstrated an association of STAT4 polymorphisms with autoimmune diseases including systemic lupus erythematosus and rheumatoid arthritis, indicating multiple autoimmune diseases share common susceptibility genes. We therefore investigated the influence of STAT4 polymorphisms on the susceptibility and phenotype of type-1 autoimmune hepatitis in a Japanese National Hospital Organization (NHO) AIH multicenter cohort study. Genomic DNA from 460 individuals of Japanese origin including 230 patients with type-1 autoimmune hepatitis and 230 healthy controls was analyzed for two single nucleotide polymorphisms in the STAT4 gene (rs7574865, rs7582694). The STAT4 rs7574865T allele conferred risk for type-1 autoimmune hepatitis (OR = 1.61, 95% CI = 1.23-2.11; P = 0.001), and patients without accompanying autoimmune diseases exhibited an association with the rs7574865T allele (OR = 1.50, 95%CI = 1.13-1.99; P = 0.005). Detailed genotype-phenotype analysis of type-1 autoimmune hepatitis patients with (n = 44) or without liver cirrhosis (n = 186) demonstrated that rs7574865 was not associated with the development of liver cirrhosis and phenotype (biochemical data and the presence of auto-antibodies). This is the first study to show a positive association between a STAT4 polymorphism and type-1 autoimmune hepatitis, suggesting that autoimmune hepatitis shares a gene commonly associated with risk for other autoimmune diseases.

  15. Association of a single nucleotide polymorphism in the C-reactive protein gene (-286) with susceptibility to Plasmodium falciparum malaria

    DEFF Research Database (Denmark)

    Giha, Hayder A; Nasr, Amre; Ekström, Mattias

    2010-01-01

    The role of inflammation in malaria pathogenesis is not fully understood, although C-reactive protein (CRP) may have a negative influence on host immunity to infections. An upstream polymorphism, -286 (C > T > A), in the CRP gene is known to influence CRP levels. In this study, a cohort of 192 Su...

  16. Thermal, spectroscopic, and ab initio structural characterization of carprofen polymorphs.

    Science.gov (United States)

    Bruni, Giovanna; Gozzo, Fabia; Capsoni, Doretta; Bini, Marcella; Macchi, Piero; Simoncic, Petra; Berbenni, Vittorio; Milanese, Chiara; Girella, Alessandro; Ferrari, Stefania; Marini, Amedeo

    2011-06-01

    Commercial and recrystallized polycrystalline samples of carprofen, a nonsteroidal anti-inflammatory drug, were studied by thermal, spectroscopic, and structural techniques. Our investigations demonstrated that recrystallized sample, stable at room temperature (RT), is a single polymorphic form of carprofen (polymorph I) that undergoes an isostructural polymorphic transformation by heating (polymorph II). Polymorph II remains then metastable at ambient conditions. Commercial sample is instead a mixture of polymorphs I and II. The thermodynamic relationships between the two polymorphs were determined through the construction of an energy/temperature diagram. The ab initio structural determination performed on synchrotron X-Ray powder diffraction patterns recorded at RT on both polymorphs allowed us to elucidate, for the first time, their crystal structure. Both crystallize in the monoclinic space group type P2(1) /c, and the unit cell similarity index and the volumetric isostructurality index indicate that the temperature-induced polymorphic transformation I → II is isostructural. Polymorphs I and II are conformational polymorphs, sharing a very similar hydrogen bond network, but with different conformation of the propanoic skeleton, which produces two different packing. The small conformational change agrees with the low value of transition enthalpy obtained by differential scanning calorimetry measurements and the small internal energy computed with density functional methods. Copyright © 2011 Wiley-Liss, Inc.

  17. 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

  18. Toll-like receptor 4 Asp299Gly and Thr399Ile polymorphisms and typhoid susceptibility in Asian Malay population in Malaysia.

    Science.gov (United States)

    Bhuvanendran, Saatheeyavaane; Hussin, Hani M; Meran, Lila P; Anthony, Amy A; Zhang, Leilei; Burch, Lauranell H; Phua, Kia K; Ismail, Asma; Balaram, Prabha

    2011-09-01

    Typhoid fever is a major health problem with frequent outbreaks in Kelantan, Malaysia. Prevalence of TLR4 gene polymorphisms varies with ethnic groups (0-20%) and predisposean individual to gram-negative infections. The prevalence rate of TLR4 Asp299Gly and Thr399lle polymorphisms in the Malay population or the influence of these on typhoid fever susceptibility is not yet reported. 250 normal and 304 susceptible Malay individuals were investigated for these polymorphisms using allele-specific PCR and analysed for its association with typhoid fever susceptibility. The total prevalence of polymorphisms in the normal population was 4.8% in comparison to 12.5% in the susceptible population (p = 0.002). An increased frequency of both polymorphisms was observed in the susceptible population (p population and suggests that these polymorphisms confer a higher risk for typhoid, infection. The higher incidence of typhoid fever in Kelantan could be attributed to the higher percentage of Malays (95%) in this state. In order to reduce the incidence of this disease, people with these polymorphisms, can be prioritised for prophylactic strategies. Copyright © 2011 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.

  19. PON1 polymorphisms are associated with polycystic ovary syndrome susceptibility, related traits, and PON1 activity in Indian women with the syndrome.

    Science.gov (United States)

    Dadachanji, Roshan; Shaikh, Nuzhat; Khavale, Sushma; Patil, Anushree; Shah, Nalini; Mukherjee, Srabani

    2015-07-01

    To investigate the association of paraoxonase 1 (PON1) polymorphisms (L55M and Q192R) with polycystic ovary syndrome (PCOS) susceptibility and its related traits in Indian women. Case-control study. Academic research institute, infertility, and endocrinology clinics. Controls (n = 326), women with PCOS (n = 482). None. Genotypic and allelic frequency distribution, genotype-phenotype association, different PON1 activities (lactonase, arylesterase, and paraoxonase). The genotypic and allelic frequency distributions of the L55M polymorphism were significantly different between lean controls and lean women with PCOS, and this polymorphism reduced the risk of PCOS development in lean but not in obese Indian women. Furthermore, this polymorphism was significantly associated with decreased 2-hour glucose, apolipoprotein B, free and bioavailable T, and free androgen index concurrent with increased sex hormone-binding globulin (SHBG) and FSH levels only in lean women with PCOS. However, Q192R polymorphism showed comparable genotypic frequency distribution between controls and women with PCOS. PON1 lactonase and arylesterase activities were significantly decreased in women with PCOS compared with controls. PON1 polymorphisms were shown to influence its activities. Our study showed that L55M, but not Q192R, polymorphism is significantly associated with reduced PCOS susceptibility only in lean women and also impacts glucose metabolism, lipid parameters, and hyperandrogenemia in them. Our study therefore suggests the possibility of differential genetic pathophysiology of PCOS between lean and obese women. Copyright © 2015 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

  20. The Impact of Drug Metabolism Gene Polymorphisms on Therapeutic Response and Survival in Diffuse Large B-Cell Lymphoma Patients.

    Science.gov (United States)

    Pál, Ildikó; Illés, Árpád; Gergely, Lajos; Pál, Tibor; Radnay, Zita; Szekanecz, Zoltán; Zilahi, Erika; Váróczy, László

    2018-04-01

    Diffuse large B-cell lymphoma (DLBCL) accounts for 30% of all non-Hodgkin lymphomas (NHL) and 80% of agressive lymphomas. Besides the traditional International Prognostic Index (IPI), some other factors may also influence the prognosis of DLBCL patients. To study how the genetic polymorphisms in the metabolic pathway influence the event-free and overall survivals and therapeutic responses in DLBCL. The study was comprised of 51 patients (32 men, 19 women). The average age was 53.1 years. DLBCL was diagnosed between 2011 and 2016 and the average follow-up time was 3.78 years. These patients received 1-8 cycles (an average of 6.2 cycles) of rituximab, cyclophosphamide, doxorubicin, vincristin, prednisolon (R-CHOP) immunochemotherapy. Real-time polymerase chain reaction was used to determine the genetic polymorphisms of CYP2E1, GSTP1, NAT1, and NAT2 genes. Our results showed that the polymorphisms of CYP2E1, GSTP1, and NAT1 genes did not influence the prognosis of DLBCL patients significantly. In terms of the NAT2 gene, GG homozygous patients showed slightly better therapeutic response and survival results compared to those bearing an A allele; however, the differences were not statistically significant. Our results could not confirm that genetic polymorphism in metabolic pathways has any predictive role in DLBCL.

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

    Science.gov (United States)

    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.

  2. Association study of interferon gamma (IFN-γ) +874T/A gene polymorphism in patients with paranoid schizophrenia.

    Science.gov (United States)

    Paul-Samojedny, Monika; Owczarek, Aleksander; Suchanek, Renata; Kowalczyk, Malgorzata; Fila-Danilow, Anna; Borkowska, Paulina; Kucia, Krzysztof; Kowalski, Jan

    2011-03-01

    Schizophrenia is a multifactorial disease with changes affecting the immune system. Dysregulation of the cytokine network in schizophrenia has been well documented. Such changes may occur due to disturbances in cytokine levels that are linked to polymorphisms of cytokine genes. However, research in the role of cytokine gene polymorphisms in schizophrenia has been surprisingly scanty. The aim of this study was to identify, in a case control study, whether polymorphism of IFN-γ gene is a risk factor for the development of paranoid schizophrenia. To the best of our knowledge, this is the first study that examines the association between the IFN-γ gene polymorphism and psychopathological symptoms in patients with paranoid schizophrenia. Polymorphism of IFN-γ (+874T/A, rs 62559044) in schizophrenic patients (n=179), as well as healthy individuals (n=196), both Polish residents, was genotyped using AS-PCR method. Of note, when analyzing the results, we took into consideration the gender of studied individuals. Surprisingly, a single-nucleotide polymorphism in the first intron of the IFN-γ gene was found to be associated with paranoid schizophrenia in males, but not in females. The presence of allele A at position +874 in the IFN-γ gene correlates with 1.66-fold higher risk of paranoid schizophrenia development in males. Differences in the genotypes may have an important role in determining the level of I gene transcription. Because other polymorphisms have been demonstrated to influence IFN-γ transcription, further analysis is necessary to clarify the role of this gene in the pathogenesis of paranoid schizophrenia.

  3. Potential genetic polymorphisms predicting polycystic ovary syndrome

    Directory of Open Access Journals (Sweden)

    Yao Chen

    2018-05-01

    Full Text Available Polycystic ovary syndrome (PCOS is a heterogenous endocrine disorder with typical symptoms of oligomenorrhoea, hyperandrogenism, hirsutism, obesity, insulin resistance and increased risk of type 2 diabetes mellitus. Extensive evidence indicates that PCOS is a genetic disease and numerous biochemical pathways have been linked with its pathogenesis. A number of genes from these pathways have been investigated, which include those involved with steroid hormone biosynthesis and metabolism, action of gonadotropin and gonadal hormones, folliculogenesis, obesity and energy regulation, insulin secretion and action and many others. In this review, we summarize the historical and recent findings in genetic polymorphisms of PCOS from the relevant publications and outline some genetic polymorphisms that are potentially associated with the risk of PCOS. This information could uncover candidate genes associating with PCOS, which will be valuable for the development of novel diagnostic and treatment platforms for PCOS patients.

  4. Raman Identification of Polymorphs in Pentacene Films

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    Alberto Girlando

    2016-04-01

    Full Text Available We use Raman spectroscopy to characterize thin films of pentacene grown on Si/SiO x by Supersonic Molecular Beam Deposition (SuMBD. We find that films up to a thickness of about 781 Å (∼ 52 monolayers all belong to the so-called thin-film (TF phase. The appearance with strong intensity of some lattice phonons suggests that the films are characterized by good intra-layer order. A comparison of the Raman spectra in the lattice and CH bending spectral regions of the TF polymorph with the corresponding ones of the high-temperature (HT and low-temperature (LT bulk pentacene polymorphs provides a quick and nondestructive method to identify the different phases.

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

    Science.gov (United States)

    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.

  6. Pathogen-group specific association between CXCR1 polymorphisms and subclinical mastitis in dairy heifers.

    Science.gov (United States)

    Verbeke, Joren; Piepers, Sofie; Peelman, Luc; Van Poucke, Mario; De Vliegher, Sarne

    2012-08-01

    The chemokine (C-X-C motif) receptor 1 (CXCR1) gene encodes the homonymous receptor for interleukin 8 (IL8) on polymorphonuclear neutrophilic leucocytes (PMNL). Binding causes migration from blood to milk, activation and prolonged survival of PMNL, a crucial process in the innate immune defence of the bovine mammary gland against invading mastitis-causing pathogens. The main objective of this study was to screen the entire coding region of the CXCR1 gene for polymorphisms and to analyse their association with udder health of dairy heifers. One-hundred-and-forty Belgian Holstein heifers originating from 20 commercial dairy farms were genotyped by DNA sequencing. Detailed phenotypic data on udder health was available including quarter bacteriological culture results and somatic cell count (SCC) in early lactation and composite milk SCC during first lactation. In total, 16 polymorphisms (including 8 missense mutations) were detected. Polymorphism c.980A>G was associated with pathogen-group specific IMI: heifers with genotype AG were less likely to have an IMI due to major mastitis pathogens compared with heifers with genotype GG but did not have less IMI by coagulase-negative staphylococci, so-called minor pathogens. CXCR1 genotype was neither associated with quarter SCC in early lactation nor with composite SCC during lactation. Although mastitis susceptibility is influenced by many factors, some genetic polymorphisms potentially have major effects on udder health of heifers, as was shown here. These results trigger us to further study the relationship between CXCR1 polymorphisms and mastitis susceptibility in both observational and experimental trials.

  7. A Study of the Impact of Death Receptor 4 (DR4) Gene Polymorphisms in Alzheimer's Disease.

    Science.gov (United States)

    Edgünlü, Tuba Gökdoğan; Ozge, Aynur; Yalın, Osman Özgür; Kul, Seval; Erdal, Mehmet Emin

    2013-09-01

    Excessive apoptosis is believed to play a role in many degenerative and non-degenerative neurological diseases including Alzheimer's disease (AD). Much recent data suggest that apoptotic mechanisms may represent the missing link between Aβ deposition and proteolysis of tau protein. However, there is emerging evidence that apoptotic mechanisms may play a role in Alzheimer's Disease pathogenesis in the absence of overt apoptosis. TNF-related apoptosis inducing ligand receptor 1 (Death Receptor 4, DR4) might impair the apoptotic signal transduction and lead to dysregulation of the homeostasis between cell survival and cell death. The aim of our study was to further investigate the relationship between genetic variants of DR4 and Alzheimer's Disease. Case control study. Sixty-eight patients with AD were included in the study. The control group comprised 72 subjects without signs of neurodegenerative diseases, as evidenced by the examination.DNA was extracted from whole blood using the salting-out procedure. Genotypes were identified by restriction fragment length polymorphism analysis of polymerase chain reaction (PCR-RFLP) products. We observed significant differences in the genotypic distribution of the rs6557634 polymorphism in AD patients compared with controls (p0.05) and the DR4 rs20576 polymorphism (p>0.05). According to haplotype analysis of the DR4 gene for rs6557634, rs20575 and rs20576 polymorphisms, GCA and GCC haplotypes might be a risk factor for AD. Also, we have shown that ACA, GGC and GGA haplotypes might be protective factors against AD. The present results indicate for the first time the possible contribution of the DR4 gene rs6557634, rs20575, rs20576 polymorphisms in Alzheimer's Disease, which may influence susceptibility to Alzheimer's Disease.

  8. Meta-analysis of microsomal epoxide hydrolase gene polymorphism and risk of hepatocellular carcinoma.

    Directory of Open Access Journals (Sweden)

    Jian-Hong Zhong

    Full Text Available BACKGROUND: Hepatocarcinogenesis is a complex process that may be influenced by many factors, including polymorphism in microsomal epoxide hydrolase (mEH. Previous work suggests an association between the Tyr113His and His139Arg mEH polymorphisms and susceptibility to hepatocellular carcinoma (HCC, but the results have been inconsistent. METHODS: PubMed, EMBASE, Google Scholar and the Chinese National Knowledge Infrastructure databases were systematically searched to identify relevant studies. A meta-analysis was performed to examine the association between Tyr113His and His139Arg mEH polymorphism and susceptibility to HCC. Odds ratios (ORs and 95% confidence intervals (95% CIs were calculated. RESULTS: Eleven studies were included in the meta-analysis, involving 1,696 HCC cases and 3,600 controls. The 113His- mEH allele was significantly associated with increased risk of HCC based on allelic contrast (OR = 1.35, 95% CI = 1.04-1.75, p = 0.02, homozygote comparison (OR = 1.65, 95% CI = 1.07-2.54, p = 0.02 and a recessive genetic model (OR = 1.54, 95% CI = 1.21-1.96, p<0.001, while individuals carrying the Arg139Arg mEH genotype had no association with increased or decreased risk of HCC. CONCLUSION: The 113His- allele polymorphism in mEH may be a risk factor for hepatocarcinogenesis, while the mEH 139Arg- allele may not be a risk or protective factor. There is substantial evidence that mEH polymorphisms interact synergistically with other genes and the environment to modulate risk of HCC. Further large and well-designed studies are needed to confirm these conclusions.

  9. Gene Polymorphism-related Individual and Interracial Differences in the Outcomes of Androgen Deprivation Therapy for Prostate Cancer.

    Science.gov (United States)

    Fujimoto, Naohiro; Shiota, Masaki; Tomisaki, Ikko; Minato, Akinori

    2017-06-01

    Among patients with prostate cancer, the prognosis after androgen deprivation therapy differs significantly among individuals and among races; however, the reasons underlying these differences are poorly understood. Several single nucleotide polymorphisms in genes associated with prostate cancer progression or castration resistance might serve as the host factor that influences prognosis and, thus, accounts for these individual and racial gaps in treatment outcomes. Accordingly, single nucleotide polymorphisms associated with treatment outcomes could be used as predictive and/or prognostic biomarkers for patient stratification and to identify personalized treatment and follow-up protocols. The present review has summarized the genetic polymorphisms that have been reported to associate with androgen deprivation therapy outcomes among patients with prostate cancer and compared the allele frequencies among different ethnic groups. Copyright © 2017 Elsevier Inc. All rights reserved.

  10. New polymorphic variants of human blood clotting factor IX

    Energy Technology Data Exchange (ETDEWEB)

    Surin, V.L.; Luk`yanenko, A.V.; Tagiev, A.F.; Smirnova, O.V. [Hematological Research Center, Moscow (Russian Federation); Plutalov, O.V.; Berlin, Yu.A. [Shemyakin Institute of Bioorganic Chemistry, Moscow (Russian Federation)

    1995-04-01

    The polymorphism of Alu-repeats, which are located in the introns of the human factor IX gene (copies 1-3), was studied. To identify polymorphic variants, direct sequencing of PCR products that contained appropriate repeats was used. In each case, 20 unrelated X chromosomes were studied. A polymorphic Dra I site was found near the 3{prime}-end of Alu copy 3 within the region of the polyA tract. A PCR-based testing system with internal control of restriction hydrolysis was suggested. Testing 81 unrelated X chromosomes revealed that the frequency of the polymorphic Dra I site is 0.23. Taq I polymorphism, which was revealed in Alu copy 4 of factor IX gene in our previous work, was found to be closely linked to Dra I polymorphism. Studies in linkage between different types of polymorphisms of the factor IX gene revealed the presence of a rare polymorphism in intron a that was located within the same minisatellite region as the known polymorphic insertion 50 bp/Dde I. However, the size of the insertion in our case was 26 bp. Only one polymorphic variant was found among over 150 unrelated X chromosomes derived from humans from Moscow and its vicinity. 10 refs., 4 figs., 1 tab.

  11. Highly polymorphic RFLP probes as diagnostic tools

    International Nuclear Information System (INIS)

    Donis-Keller, H.; Barker, D.F.; Knowlton, R.G.; Schumm, J.W.; Braman, J.C.; Green, P.

    1986-01-01

    In this paper, we describe the identification of highly polymorphic RFLP loci and their application to genotyping in humans and to mapping the CF gene to chromosome 7. We also report the construction of a high-resolution genetic map of chromosome 7 and summarize progress toward the development of a presymptomatic diagnostic test for CF that should be useful in virtually every case. 25 references, 7 figures, 5 tables

  12. Similarity-based Polymorphic Shellcode Detection

    Directory of Open Access Journals (Sweden)

    Denis Yurievich Gamayunov

    2013-02-01

    Full Text Available In the work the method for polymorphic shellcode dedection based on the set of known shellcodes is proposed. The method’s main idea is in sequential applying of deobfuscating transformations to a data analyzed and then recognizing similarity with malware samples. The method has been tested on the sets of shellcodes generated using Metasploit Framework v.4.1.0 and PELock Obfuscator and shows 87 % precision with zero false positives rate.

  13. Polymorphism of lipid self-assembly systems

    International Nuclear Information System (INIS)

    Takahashi, Hiroshi

    2002-01-01

    When lipid molecules are dispersed into an aqueous medium, various self-organized structures are formed, depending on conditions (temperature, concentration, etc), in consequence of the amphipathic nature of the molecules. In addition, lipid self-assembly systems exhibit polymorphic phase transition behavior. Since lipids are one of main components of biomembranes, studies on the structure and thermodynamic properties of lipid self-assembly systems are fundamentally important for the consideration of the stability of biomembranes. (author)

  14. Serotonin transporter polymorphism modifies the association between depressive symptoms and sleep onset latency complaint in elderly people: results from the 'InveCe.Ab' study.

    Science.gov (United States)

    Polito, Letizia; Davin, Annalisa; Vaccaro, Roberta; Abbondanza, Simona; Govoni, Stefano; Racchi, Marco; Guaita, Antonio

    2015-04-01

    Previous studies have documented the involvement of the central nervous system serotonin in promoting wakefulness. There are few and conflicting results over whether there is an actual association between bearing the short allele of serotonin transporter promoter polymorphism (5-HTTLPR) and worse sleep quality. This study examined whether sleep onset latency complaint is associated with the 5-HTTLPR triallelic polymorphism in the SLC6A4 gene promoter and whether this polymorphism influences the relationship between sleep onset latency complaint and depressive symptoms in elderly people. A total of 1321 community-dwelling individuals aged 70-74 years were interviewed for sleep onset latency complaint and for sleep medication consumption. Participants' genomic DNA was typed for 5-HTTLPR and rs25531 polymorphisms. Depressive symptoms were evaluated with the Geriatric Depression Scale Short form and general medical comorbidity was assessed by the Cumulative Illness Rating Scale. The presence of a past history of depression was recorded. The S' allele of the 5-HTTLPR triallelic polymorphism was associated with sleep onset latency complaint. This association was maintained after adjusting for depressive symptoms, sex, age, history of depression and medical comorbidity. After stratification for 5-HTTLPR/rs25531, only in S'S' individuals high depressive symptoms were actually associated with sleep onset latency complaint. These data indicate that the low-expressing 5-HTTLPR triallelic polymorphism is an independent risk factor for sleep onset latency disturbance. Furthermore, the 5-HTTLPR genotype influences the association between depressive symptoms and sleep onset latency complaint. © 2014 European Sleep Research Society.

  15. Investigation of -308G>A and -1031T>C polymorphisms in the TNFA promoter region in Polish peptic ulcer patients.

    Science.gov (United States)

    Sałagacka, Aleksandra; Żebrowska, Marta; Jeleń, Agnieszka; Mirowski, Marek; Balcerczak, Ewa

    2014-11-01

    Tumor necrosis factor α (TNF-α) encoded by TNFA is a key mediator in inflammation, a precursor condition for peptic ulceration. Promoter polymorphisms of TNFA that influence its transcriptional activity and TNF-α production are known. TNFA-308G>A (rs1800629) and TNFA-1031T>C (rs1799964), which are responsible for increased TNFA transcription, could influence the risk of peptic ulceration. This study aimed to investigate these polymorphisms and to evaluate their association with peptic ulcer disease and Helicobacter pylori infection in the Polish population. Gastric mucosa specimens obtained from 177 Polish peptic ulcer patients were used to conduct rapid urease tests and to assess the investigated polymorphisms by polymerase chain reaction-restriction fragment length polymorphism. Genotyping data were compared with the results obtained from healthy individuals of Polish origin. There were no significant differences in genotype and allele frequency of the investigated polymorphisms between peptic ulcer patients and healthy individuals. No associations between the frequencies of particular genotypes and alleles for both single-nucleotide polymorphisms (SNPs) and the presence of H. pylori infection in peptic ulcer patients and in subgroups of men and women with peptic ulcer disease were found. The investigated SNPs are not risk factors for either peptic ulcer or H. pylori infection development in the Polish population. The results require verification in a larger cohort.

  16. NOS3 Polymorphisms and Chronic Kidney Disease

    Directory of Open Access Journals (Sweden)

    Alejandro Marín Medina

    2018-05-01

    Full Text Available ABSTRACT Chronic kidney disease (CKD is a multifactorial pathophysiologic irreversible process that often leads to a terminal state in which the patient requires renal replacement therapy. Most cases of CKD are due to chronic-degenerative diseases and endothelial dysfunction is one of the factors that contribute to its pathophysiology. One of the most important mechanisms for proper functioning of the endothelium is the regulation of the synthesis of nitric oxide. This compound is synthesized by the enzyme nitric oxide synthase, which has 3 isoforms. Polymorphisms in the NOS3 gene have been implicated as factors that alter the homeostasis of this mechanism. The Glu298Asp polymorphisms 4 b/a and -786T>C of the NOS3 gene have been associated with a more rapid deterioration of kidney function in patients with CKD. These polymorphisms have been evaluated in patients with CKD of determined and undetermined etiology and related to a more rapid deterioration of kidney function.

  17. 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...

  18. Roles of Beta2- and Beta3-Adrenoceptor Polymorphisms in Hypertension and Metabolic Syndrome

    Directory of Open Access Journals (Sweden)

    Kazuko Masuo

    2010-01-01

    gain, and the sympathetic nervous system participates in regulating energy balance through thermogenesis. The thermogenic effects of catecholamines in obesity have been mainly mediated via the 2- and 3-adrenergic receptors in humans. Further, 2-adrenoceptors importantly influence vascular reactivity and may regulate blood pressure. Genetic polymorphistns of the -adrenoceptor gene have been shown to alter the function of several adrenoceptor subtypes and thus to modify the response to catecholamine. 2-adrenoceptor polymorphisms (Arg16Gly, Gln27Glu, and Thr164Ile have been studied in relation to hypertension. Genetic variations in the 3-adrenoceptor (i.e. Try64Arg variant are also associated with both obesity and hypertension. However, the precise relationships of the polymorphisms of 2- and 3-adrenoceptor genes with sympathetic nervous system activity, hypertension, and metabolic syndrome have not been fully clarified. This paper will discuss the current topics involving the influence of the sympathetic nervous system and 2- and 3- adrenoceptor polymorphisms in hypertension and metabolic syndrome.

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

    Science.gov (United States)

    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.

  20. Genetic polymorphisms in folate pathway enzymes, DRD4 and GSTM1 are related to temporomandibular disorder

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    Mayor-Olea Alvaro

    2011-05-01

    Full Text Available Abstract Background Temporomandibular disorder (TMD is a multifactorial syndrome related to a critical period of human life. TMD has been associated with psychological dysfunctions, oxidative state and sexual dimorphism with coincidental occurrence along the pubertal development. In this work we study the association between TMD and genetic polymorphisms of folate metabolism, neurotransmission, oxidative and hormonal metabolism. Folate metabolism, which depends on genes variations and diet, is directly involved in genetic and epigenetic variations that can influence the changes of last growing period of development in human and the appearance of the TMD. Methods A case-control study was designed to evaluate the impact of genetic polymorphisms above described on TMD. A total of 229 individuals (69% women were included at the study; 86 were patients with TMD and 143 were healthy control subjects. Subjects underwent to a clinical examination following the guidelines by the Research Diagnostic Criteria for Temporomandibular Disorders (RDC/TMD. Genotyping of 20 Single Nucleotide Polymorphisms (SNPs, divided in two groups, was performed by multiplex minisequencing preceded by multiplex PCR. Other seven genetic polymorphisms different from SNPs (deletions, insertions, tandem repeat, null genotype were achieved by a multiplex-PCR. A chi-square test was performed to determine the differences in genotype and allelic frequencies between TMD patients and healthy subjects. To estimate TMD risk, in those polymorphisms that shown significant differences, odds ratio (OR with a 95% of confidence interval were calculated. Results Six of the polymorphisms showed statistical associations with TMD. Four of them are related to enzymes of folates metabolism: Allele G of Serine Hydoxymethyltransferase 1 (SHMT1 rs1979277 (OR = 3.99; 95%CI 1.72, 9.25; p = 0.002, allele G of SHMT1 rs638416 (OR = 2.80; 95%CI 1.51, 5.21; p = 0.013, allele T of Methylentetrahydrofolate

  1. The impact of HLA-G, LILRB1 and LILRB2 gene polymorphisms on susceptibility to and severity of endometriosis.

    Science.gov (United States)

    Bylińska, Aleksandra; Wilczyńska, Karolina; Malejczyk, Jacek; Milewski, Łukasz; Wagner, Marta; Jasek, Monika; Niepiekło-Miniewska, Wanda; Wiśniewski, Andrzej; Płoski, Rafał; Barcz, Ewa; Roszkowski, Piotr; Kamiński, Paweł; Malinowski, Andrzej; Wilczyński, Jacek R; Radwan, Paweł; Radwan, Michał; Kuśnierczyk, Piotr; Nowak, Izabela

    2018-06-01

    Endometriosis is a disease in which endometriotic tissue occurs outside the uterus. Its pathogenesis is still unknown. The most widespread hypothesis claims that ectopic endometrium appears as a result of retrograde menstruation and its insufficient elimination by immunocytes. Some reports have shown expression of non-classical HLA-G molecules on ectopic endometrium. HLA-G is recognized by KIR2DL4, LILRB1 and LILRB2 receptors on natural killer (NK) and other cells. These receptors are polymorphic, which may affect their activity. In this study we investigated whether HLA-G, KIR2DL4, LILRB1 and LILRB2 polymorphisms may influence susceptibility to endometriosis and disease progression. We used polymerase chain reaction (PCR), PCR-restriction fragment length polymorphism (PCR-RFLP) and allelic discrimination methods with TaqMan SNP Genotyping Assays for typing of 276 patients with endometriosis and 314 healthy fertile women. The HLA-G rs1632947:GG genotype was associated with protection against the disease and its severe stages; HLA-G rs1233334:CT protected against progression; LILRB1 rs41308748:AA and LILRB2 rs383369:AG predisposed to the disease and its progression. No effect of KIR2DL4 polymorphism was observed. These results support the role of polymorphisms of HLA-G and its receptors LILRB1 and LILRB2 in susceptibility to endometriosis and its progression.

  2. The Effect of IL-4 Gene Polymorphisms on Cytokine Production in Patients with Chronic Periodontitis and in Healthy Controls

    Directory of Open Access Journals (Sweden)

    Jirina Bartova

    2014-01-01

    Full Text Available Chronic periodontitis (CP is an inflammatory disease of the teeth-supporting tissues in which genetic predisposition, dental plaque bacteria, and immune mechanisms all play important roles. The aim of this study was to evaluate the occurrence of IL-4 gene polymorphisms in chronic periodontitis and to investigate the association between polymorphisms and cytokines production after bacterial stimulation. Sixty-two subjects (47 CP patients and 15 healthy controls with detected two polymorphisms in the IL-4 gene (-590C/T and intron 3 VNTR were examined. Production of cytokines (IL-1α, IL-1β, IL-4, IL-5, IL-6, IL-10, IL-17, TNFα, INFγ, and VEGF was studied after in vitro stimulation of isolated peripheral blood by mitogens (Pokeweed mitogen, Concanavalin A, dental plaque bacteria (Aggregatibacter actinomycetemcomitans, Tannerella forsythia, Porphyromonas gingivalis, and Prevotella intermedia, and Heat Shock Protein (HSP 70 by the Luminex multiplex cytokine analysis system. The results were correlated with IL-4 genotypes in patients with CP and healthy controls. The mononuclear cells isolated from peripheral blood of CP patients with selected IL-4 polymorphisms significantly altered the production of IFNγ, IL-10, IL-1β, IL-1α, TNFα, and IL-6 after stimulation by HSP 70 or selected bacteria (from P<0.001 to P<0.05. IL-4 gene polymorphisms may influence the function of mononuclear cells to produce not only interleukin-4 but also other cytokines, especially in patients with CP.

  3. Paraoxonase 1 polymorphisms and haplotypes and the risk for having offspring affected with spina bifida in Southeast Mexico.

    Science.gov (United States)

    Gonzalez-Herrera, Lizbeth; Martín Cerda-Flores, Ricardo; Luna-Rivero, Marianne; Canto-Herrera, Jorge; Pinto-Escalante, Doris; Perez-Herrera, Norma; Quintanilla-Vega, Betzabet

    2010-11-01

    Spina bifida (SB) is a common congenital malformation in Southeast Mexico. Parents of children with SB reside in areas with frequent pesticide spraying or have agriculture activities, suggesting potential exposure to pesticides. Paraoxonase 1 (PON1) is the responsible enzyme for deactivation of organophosphates (OP) in the central nervous system. Polymorphisms of PON1 genes influence the catalytic activity and plasma protein level of the enzyme, therefore, genotypic characterization of PON1 gene represents a potential predictor for susceptibility to OP-related effects. The frequency of PON1 haplotypes and polymorphisms (-108CT, L55M, and Q192R) were determined in this study. A case-control study was performed to evaluate the risk for having offspring affected by SB in 152 cases and 160 control parents. Polymorphisms were determined by PCR amplification and restriction fragment length polymorphism and Real Time-PCR. Odds ratios and confidence interval 95% were estimated. Genotype frequencies for the three PON1 polymorphisms were distributed according to Hardy-Weinberg expectations (p > 0.05) and were significantly different between cases and controls (p Mexico. © 2010 Wiley-Liss, Inc.

  4. No association of the Arg51Gln and Leu72Met polymorphisms of the ghrelin gene and polycystic ovary syndrome.

    Science.gov (United States)

    Wang, Kehua; Wang, Leiguang; Zhao, Yueran; Shi, Yuhua; Wang, Laicheng; Chen, Zi-Jiang

    2009-02-01

    Ghrelin plays a role in regulating glucose metabolism and energy balance. Polymorphisms in preproghrelin and ghrelin gene could be responsible for obesity, insulin resistance and low ghrelin levels observed in some individuals. The objective of this study was to evaluate the influence of two single-nucleotide polymorphisms (SNPs) of ghrelin gene on the clinical, the hormonal and metabolic features in women with polycystic ovary syndrome (PCOS) in a Chinese population. A large sample of Chinese PCOS (n = 271) women and a control group (n = 296) of healthy women matched for age were studied. Hormone and metabolic profiles were measured and blood samples were collected for genotype and allelic frequency analysis. Non-synonymous SNPs in the coding region (exon 2) of the preproghrelin gene (Arg51Gln (346 G>A) and Leu72Met (408 C>A) were studied using PCR and restriction fragment length polymorphism analysis. The polymorphism Arg51Gln was not found in the cohorts studied. The distribution of Leu72Met was similar in PCOS group and in healthy controls. There was no significant difference in age, BMI, waist-hip-ratio and levels of FSH, LH, estradiol, testosterone and prolactin between PCOS patients with different genotypes, and the level of plasma glucose and insulin was also similar. No association was found between Leu72Met and Arg51Gln polymorphisms in the ghrelin gene and PCOS in Chinese population.

  5. C-reactive protein gene polymorphisms and myocardial infarction risk: a meta-analysis and meta-regression.

    Science.gov (United States)

    Zhu, Yanbin; Liu, Tongku; He, Haitao; Sun, Yuqing; Zhuo, Fengling

    2013-12-01

    C-reactive protein (CRP), the classic acute-phase protein, plays an important role in the etiology of myocardial infarction (MI). Emerging evidence has shown that the common polymorphisms in the CRP gene may influence an individual's susceptibility to MI; but individually published studies showed inconclusive results. This meta-analysis aimed to derive a more precise estimation of the associations between CRP gene polymorphisms and MI risk. A literature search of PubMed, Embase, Web of Science, and China BioMedicine (CBM) databases was conducted on articles published before June 1st, 2013. Crude odds ratio (OR) with 95% confidence interval (CI) were calculated. Nine case-control studies were included with a total of 2992 MI patients and 4711 healthy controls. The meta-analysis results indicated that CRP rs3093059 (T>C) polymorphism was associated with decreased risk of MI, especially among Asian populations. However, similar associations were not observed in CRP rs1800947 (G>C) and rs2794521 (G>A) polymorphisms (all p>0.05) among both Asian and Caucasian populations. Univariate and multivariate meta-regression analyses showed that ethnicity may be a major source of heterogeneity. No publication bias was detected in this meta-analysis. In conclusion, the current meta-analysis indicates that CRP rs3093059 (T>C) polymorphism may be associated with decreased risk of MI, especially among Asian populations.

  6. Identification of an ionotropic glutamate receptor AMPA1/GRIA1 polymorphism in crossbred beef cows differing in fertility.

    Science.gov (United States)

    Cushman, R A; Miles, J R; Rempel, L A; McDaneld, T G; Kuehn, L A; Chitko-McKown, C G; Nonneman, D; Echternkamp, S E

    2013-06-01

    A proposed functional polymorphism in the ionotropic glutamate receptor AMPA1 (GRIA1) has been reported to influence antral follicle numbers and fertility in cows. Repeat breeder cows that fail to produce a calf in multiple seasons have been reported to have reduced numbers of small (1 to 3 mm) antral follicles in their ovaries. Therefore, we tested the hypothesis that this GRIA1 polymorphism was affecting antral follicle numbers in repeat breeder cows. Repeat breeder cows (n = 64) and control cows (n = 72) that had always produced a calf were housed in a dry lot and observed twice daily for behavioral estrus. Blood samples were collected, and cows were genotyped for this GRIA1 polymorphism and for a polymorphism in the GnRH receptor (GnRHR) that was proposed to influence age at puberty. On d 3 to 8 after estrus cows were slaughtered, and reproductive organs were collected to determine antral follicle count, ovary size, and uterine horn diameter. Repeat breeder cows were older at first calving than control cows (P = 0.006). The length (P = 0.03) and height (P = 0.02) of the ovary contralateral to the corpus luteum (CL) were greater in control cows than repeat breeder cows. The endometrial diameter in the horn ipsilateral to the CL was greater in the control cows than the repeat breeder cows. Repeat breeder cows had fewer small (1 to 5 mm) antral follicles than control cows (P = 0.003); however, there was no association between GRIA1 genotype and antral follicle number. The GnRHR polymorphism was associated with age at first calving because cows that were homozygous for the C allele had a greater age at first calving than heterozygous cows or cows that were homozygous for the T allele (P = 0.01). In the granulosa cells from small (1 to 5 mm) antral follicles, mRNA abundances of 2 markers of oocyte quality, anti-Müllerian hormone and pentraxin 3, did not differ between fertility groups (P ≥ 0.12). We conclude that this GRIA1 polymorphism exists in beef cows but

  7. BCL2-like 11 intron 2 deletion polymorphism is not associated with non-small cell lung cancer risk and prognosis.

    Science.gov (United States)

    Cho, Eun Na; Kim, Eun Young; Jung, Ji Ye; Kim, Arum; Oh, In Jae; Kim, Young Chul; Chang, Yoon Soo

    2015-10-01

    BCL2-Like 11(BIM), which encodes a BH3-only protein, is a major pro-apoptotic molecule that facilitates cell death. We hypothesized that a BIM intron 2 deletion polymorphism increases lung cancer risk and predicts poor prognosis in non-small lung cancer (NSCLC) patients. We prospectively recruited 450 lung cancer patients and 1:1 age, sex, and smoking status matched control subjects from February 2013 to April 2014 among patients treated at Severance, Gangnam Severance, and Chonnam Hwasoon Hospital. The presence of a 2903-bp genomic DNA deletion polymorphism of intron 2 of BIM was analyzed by PCR and validated by sequencing. Odds ratios were calculated by chi-square tests and survival analysis with Kaplan-Meier estimation. Sixty-nine out of 450 (15.3%) lung cancer patients carried the BIM deletion polymorphism, while 66 out of 450 (14.7%) control subjects carried the BIM deletion polymorphism, with an odds ratio of for lung cancer of 1.054 (95% CI; 0.731-1.519). We categorized 406 NSCLC patients according to the presence of the polymorphism and found that there were no statistically significant differences in age, sex, histologic type, or stage between subjects with and without the deletion polymorphism. The BIM deletion polymorphism did not influence overall survival (OS) or progression free survival (PFS) in our sample (OS; 37.6 vs 34.4 months (P=0.759), PFS; 49.6 vs 26.0 months (P=0.434)). These findings indicate that the BIM deletion polymorphism is common in Korean NSCLC patients but does not significantly affect the intrinsic biologic function of BH3-only protein. Furthermore, the BIM deletion polymorphism did not predict clinical outcomes in patients with NSCLC. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  8. Association of Helicobacter pylori infection with Toll-like receptor-4 Thr399Ile polymorphism increased the risk of peptic ulcer development in North of Iran.

    Science.gov (United States)

    Tourani, Mehdi; Habibzadeh, Maryam; Shokri-Shirvani, Javad; Teymournejad, Omid; Mostafazadeh, Amrollah; Khafri, Soraya; Nouri, Hamid Reza

    2018-01-01

    Toll-like receptor-4 (TLR4) polymorphisms may influence host immune response against Helicobacter pylori (H. pylori). This study aimed to investigate whether TLR4 polymorphisms are associated with H. pylori susceptibility and risk of peptic ulcer development or not. The TLR4 + 3725 G/C polymorphism was studied using polymerase chain reaction with confronting two-pair primers (PCR-CTPP). In addition, TLR4 Asp299Gly and Thr399Ile polymorphisms were evaluated by PCR-restriction fragment length polymorphism (RFLP). There was no significant difference in TLR4 + 3725 G/C and Asp299Gly genotype frequencies between non-peptic ulcer (NPUD) and peptic ulcer (PUD) individuals in the context of peptic ulcer development and susceptibility to infection with H. pylori. Nevertheless, a significant association with increased risk for PUD development was observed for polymorphism TLR4 Thr399Ile [odds ratio (OR) = 4.2; 95% confidence interval (CI) = 1.35-13.26; p = 0.01]. Correspondingly, TLR4 Thr399Ile polymorphism was associated with H. pylori susceptibility (OR = 0.27; 95% CI = 0.08-0.88; p = 0.04). In addition, TLR4 Thr399Ile polymorphism increased 4.2-fold, the risk of peptic ulcer development in individuals infected by H. pylori carrying CT + TT genotype. Our results showed that TLR4 Thr399Ile polymorphism along with H. pylori infection may play critical roles in peptic ulcer development in North of Iran. © 2017 APMIS. Published by John Wiley & Sons Ltd.

  9. Cooling Crystallization of Indomethacin: Effect of Supersaturation, Temperature and Seeding on Polymorphism and Crystal Size Distribution

    DEFF Research Database (Denmark)

    Malwade, Chandrakant Ramkrishna; Qu, Haiyan

    2018-01-01

    In this work, effect of crystallization parameters i.e., supersaturation, seeding, and temperature on polymorphism and crystal size of a non-steroidal anti-inflammatory drug, indomethacin (IMC), was investigated. Firstly, several crystallization solvents (ethanol, methanol, ethyl acetate, acetone...... of IMC from ethanol confirmed that the supersaturation, operating temperature and seeding does affect the polymorphism as well as crystal size distribution of IMC. Fine needle shaped crystals of metastable α-IMC were obtained at 5 °C with high supersaturation even in presence of γ-IMC seeds, while...... rhombic plates like crystals of thermodynamically stable γ-IMC were obtained in remaining experiments. The amount of seed loading only marginally influenced the crystal growth rate and median particle diameter (d50). Particle size analysis of crystals obtained showed bimodal distribution in all...

  10. Association Between Genetic Polymorphisms and Pain Sensitivity in Patients with Hip Osteoarthritis

    DEFF Research Database (Denmark)

    Olesen, Anne E; Nielsen, Lecia M; Feddersen, Søren

    2018-01-01

    , kappa, and delta opioid receptor genes (OPRM1, OPRK1, and OPRD1) and the catechol-O-methyltransferase gene (COMT) influenced the pain phenotype in patients with osteoarthritis. METHODS: The frequencies of 17 polymorphisms were examined. Pain sensitivity was assessed preoperatively by (1) hip rotation......BACKGROUND: Factors such as age, gender, and genetic polymorphisms may explain individual differences in pain phenotype. Genetic associations with pain sensitivity have previously been investigated in osteoarthritis patients, with a focus on the P2X7, TRPV1, and TACR1 genes. However, other genes...... may play a role as well. Osteoarthritis is a common joint disease, and many patients suffering from this disease are thought to have increased sensitivity to noxious stimuli resulting from sensitization in the nociceptive system. The aim of this study was to investigate if genetic variants of mu...

  11. Kynurenine 3-monooxygenase polymorphisms: relevance for kynurenic acid synthesis in patients with schizophrenia and healthy controls

    DEFF Research Database (Denmark)

    Holtze, Maria; Saetre, Peter; Engberg, Göran

    2012-01-01

    on the activity of kynurenine 3-monooxygenase (KMO), the enzyme converting kynurenine to 3-hydroxykynurenine. Methods: We analyzed the association between KMO gene polymorphisms and CSF concentrations of KYNA in patients with schizophrenia and healthy controls. Fifteen single nucleotide polymorphisms (SNPs) were...... selected covering KMO and were analyzed in UNPHASED. Results: We included 17 patients with schizophrenia and 33 controls in our study. We found an association between a KMO SNP (rs1053230), encoding an amino acid change of potential importance for substrate interaction, and CSF concentrations of KYNA....... Limitations: Given the limited sample size, the results are tentative until replication. Conclusion: Our results suggest that the nonsynonymous KMO SNP rs1053230 influences CSF concentrations of KYNA....

  12. Kynurenine 3-monooxygenase polymorphisms: relevance for kynurenic acid synthesis in patients with schizophrenia and healthy controls.

    Science.gov (United States)

    Holtze, Maria; Saetre, Peter; Engberg, Göran; Schwieler, Lilly; Werge, Thomas; Andreassen, Ole A; Hall, Håkan; Terenius, Lars; Agartz, Ingrid; Jönsson, Erik G; Schalling, Martin; Erhardt, Sophie

    2012-01-01

    Patients with schizophrenia show increased brain and cerebrospinal fluid (CSF) concentrations of the endogenous N-methyl-D-aspartate receptor antagonist kynurenic acid (KYNA). This compound is an end-metabolite of the kynurenine