AgNOR polymorphism association with squamous intraepithelial lesions and invasive carcinoma with HPV infection Asociación de los polimorfismos AgNORs con lesiones intraepiteliales escamosas, carcinoma cervical e infección por VPH
Luz del Carmen Alarcón-Romero
Full Text Available OBJECTIVE: Evaluate the relationships between AgNORs polymorphisms and squamous intraepithelial lesions (SIL and squamous cell carcinoma (SCC with HPV infection. MATERIALS AND METHODS: A study was carried out on sixty women from the state of Guerrero, Mexico. HPV detection was performed by PCR. AgNORs were identified by argentic impregnation. One hundred cells per slide were counted and classified according to the polymorphism of AgNORs dots; typical (spherical and atypical (large, kidney-shaped and clustered. RESULTS: A total of 100% of the cases were positive for HPV infection. Nine different high-risk HPV genotypes were found, type16 was the most common (48.6%. The AgNORs showed a significant decrease in spherical shape according to neoplastic development. The three atypical shapes showed a significant increase in SIL and SCC (p-trendOBJETIVO: Evaluar la relación entre los polimorfismos de AgNORs con las lesiones intraepiteliales escamosas (LIE y carcinoma de células escamosas (CCE. MATERIAL Y MÉTODOS: Se estudiaron sesenta mujeres del estado de Guerrero, México. La detección del VPH fue por PCR y los AgNORs por impregnación argéntica; se contaron 100 células y se clasificaron por tipo de polimorfismo de AgNORs: típico (esférico y atípicos (largo, forma de riñón o de racimo. RESULTADOS: El 100% de los casos presentaron infección por VPH, se encontraron nueve genotipos diferentes de VPH de alto riesgo, el 16 fue el más común (48.6%. La forma esférica de los polimorfismos de AgNORs mostró una disminución con el desarrollo neoplásico y las atípicas incrementaron progresivamente con SIL y SCC (p-tendencia<0.001. CONCLUSIONES: Los polimorfismos AgNORs se incrementan progresivamente con el grado de lesión histológica, y pueden ser útiles en el pronóstico de progresión del carcinoma cervical.
Full Text Available In an attempt to investigate the neoplastic progression in different stages of actinic keratosis (AK, a standardized AgNOR analysis was performed in 94 cases of AK, 35 of which were associated with squamous cell carcinoma (SCC or basal cell carcinoma (BCC, and in 31 cases of SCC and 22 cases of BCC. The cases were subdivided into low- and high- AgNOR-expressing (AgNOR status AK by using the mean area of AgNORs per cell (NORA value (3.996 ?m2 as the cut-off. In AK samples, a progressive increase of the mean NORA value from Stage I to Stage IV was encountered. In addition, a significantly higher mean NORA value was found in the AK cases associated with SCC, in comparison to those without SCC; by contrast, no significant differences in the mean NORA value were noted between AK cases with or without BCC. A highly significant association between a high AgNOR quantity and the coexistence of SCC was encountered in AK; no association was appreciable between the AgNOR quantity and the co-occurrence of BCC. Moreover, when the co-existence of SCC in AK was considered as the reference point, the AK cases associated with SCC mostly (95.5% presented a high AgNOR quantity (high sensitivity, but only 57.6% of cases without SCC displayed a low AgNOR quantity (low specificity. Additionally, our data document that the standardised AgNOR analysis represents a strong negative predictor for the association between SCC and AK. Indeed, a low AgNOR quantity mostly is associated with AK cases without SCC.
Anushree Sharma; Susmita Saxena
Background: Nucleolar organizer regions (NOR) are associated with proliferative activity and represent a diagnostic and prognostic marker. Materials and Methods: Smears were taken from smokers, tobacco chewers, oral squamous cell carcinoma patients, and normal subjects and evaluated by 2 silver-staining nucleolar organizer region (AgNOR) counting methods: (1) mean number of AgNORs per nucleus (mAgNOR); and (2) percentage of nuclei with >3 and >5 AgNORs (pAgNOR). Results: A statistic...
Full Text Available AgNOR and MIB-1 are marker for breast cancer cell proliferation and can be use as based for radiotherapy treatment after surgery. Value of AgNOR and MIB-1 index were determined using staining and immunohistochemistry staining method respectively from 25 of microscopic slides of breast cancer tissue patients with surgery, and grouped based on degree of differentiation, 3 slides were good degree (G1, 16 slides were medium degree (G2 and 6 slides were poor degree (between G2 and G3. The result shown that the value of AgNOR and MIB-1 index were tended to increase with the increased differentiation degree. There was a positive correlation between the value of AgNOR and index of MIB-1 in all group of differentiation degree (r = 0.21, there is a negative correlation between AgNOR and MIB-1 on G1 (r =-0,97, positive correlation in G2 (r = 0.36 as well as positive correlation between G2 and G3 (r = 0.33. The positive correlation between AgNOR and MIB-1 were associated to the increased of G1, S and G2 phase in the proliferation cell and an increase of cells undergoing mitosis. The negative correlation were caused by the different cell proportion in G1, S and G2 phase, and undergoing mitotis.
Zou Jixing(邹记兴); Hu Chaoqun; Xiang Wenzhou; Yu Qixing; Zhou Fei
The chromosome specimens of Epinephelus malabaricus (Bloch & Schneider, 1801) are obtained from metaphase of kindney cell by vivi-injection of PHA and culture of colchicines, hypatoic-air drying technique, and then by studying their Giemsa stain, C-bands and AgNORs. The results are as follows: (1)E. malabaricus has a diploid chromosome number of 48 and its karyotype formula is 48t, NF=48, sex chromosome is not found. (2) There is a pair of chromosomes with secondary constriction near the centromere of chromosome t24. (3) 1～4 nucleoli appear in the nucleus of interphase, 55% nuclei has 1 nucleolus and only 2% for 4 nucleoli. (4) AgNORs appear in the chromosome t24 of 50% metaphase, sometimes in the chromosome t5, but not in other chromosomes. (5) The AgNORs polymorphisms are individually specific, 1～4 pairs of the number, and the frequency of 4 AgNORs are lowest. (6) The secondary constrictions and positive C-bands are coincident, close to the centromere of the chromosome, and mass constrictive heterochromatins appear in that region. (7) All the centromeres of chromosomes are darkly stained C-bands, and the whole arm of chromosome t24 and its centromere are same positive C-bands. (8) The evolutive regulation of the karyotype and the developing mechanism of AgNORs and C-bands are discussed.
Kripke, Daniel F; Nievergelt, Caroline M; Joo, EJ; Shekhtman, Tatyana; Kelsoe, John R.
Background: Clinical symptoms of affective disorders, their response to light treatment, and sensitivity to other circadian interventions indicate that the circadian system has a role in mood disorders. Possibly the mechanisms involve circadian seasonal and photoperiodic mechanisms. Since genetic susceptibilities contribute a strong component to affective disorders, we explored whether circadian gene polymorphisms were associated with affective disorders in four complementary studies.Methods:...
Nikicicz, E P; Norback, D. H.
Fifteen normal bone marrow aspirates were stained with the agyrophilic nucleolar organiser region (AgNOR) method. The results of the specific staining AgNORs as well as nuclear and cytoplasmic staining were analysed. A system was devised to characterise precisely the AgNORs present in the nuclei of bone marrow cells. Particular types of bone marrow cells had a characteristic AgNOR and non-AgNOR staining pattern. The bone marrow cells were identified easily and reliably with AgNOR staining and...
Deuster, Patricia A; Contreras-Sesvold, Carmen L; O'Connor, Francis G; Campbell, William W; Kenney, Kimbra; Capacchione, John F; Landau, Mark E; Muldoon, Sheila M; Rushing, Elisabeth J; Heled, Yuval
Exertional rhabdomyolysis (ER) occurs in young, otherwise healthy, individuals principally during strenuous exercise, athletic, and military training. Although many risk factors have been offered, it is unclear why some individuals develop ER when participating in comparable levels of physical exertion under identical environmental conditions and others do not. This study investigated possible genetic polymorphisms that might help explain ER. DNA samples derived from a laboratory-based study of persons who had never experienced an episode of ER (controls) and clinical ER cases referred for testing over the past several years were analyzed for single nucleotide polymorphisms (SNPs) in candidate genes. These included angiotensin I converting enzyme (ACE), α-actinin-3 (ACTN3), creatine kinase muscle isoform (CKMM), heat shock protein A1B (HSPA1B), interleukin 6 (IL6), myosin light chain kinase (MYLK), adenosine monophosphate deaminase 1 (AMPD1), and sickle cell trait (HbS). Population included 134 controls and 47 ER cases. The majority of ER cases were men (n = 42/47, 89.4 %); the five women with ER were Caucasian. Eighteen African Americans (56.3 %) were ER cases. Three SNPs were associated with ER: CKMM Ncol, ACTN3 R577X, and MYLK C37885A. ER cases were 3.1 times more likely to have the GG genotype of CKMM (odds ratio/OR = 3.1, confidence interval/CI 1.33-7.10), 3.0 times for the XX genotype of ACTN3 SNP (OR = 2.97, CI 1.30-3.37), and 5.7 times for an A allele of MYLK (OR = 21.35, CI 2.60-12.30). All persons with HbS were also ER cases. Three distinct polymorphisms were associated with ER. Further work will be required to replicate these findings and determine the mechanism(s) whereby these variants might confer susceptibility. PMID:23543093
Zhang, Xiaoyu; Zhou, Xingtao; Qu, Xinhua
Background: The potential association between IGF-1 polymorphisms and high myopia has been investigated in previous studies, but the actual relationship remains controversial. Accordingly, we conducted a meta-analysisincludingcase-control and cohort studies to assess the existing relationship between high myopia and IGF-1 polymorphisms. We searched MEDLINE, EMBASE, and OVID. Odds ratios (OR) with 95% confidence intervals (CI) were derived for single-nucleotide polymorphisms (SNPs) involved in...
Doetzer, Andrea D; Brancher, João A; Pecharki, Giovana D; Schlipf, Nina; Werneck, Renata; Mira, Marcelo T; Riess, Olaf; Bauer, Peter; Trevilatto, Paula Cristina
Dental caries is a common multifactorial disease, resulting from the interaction of biofilm, cariogenic diet and host response over time. Lactotransferrin (LTF) is a main salivary glycoprotein, which modulates the host immune-inflammatory and antibacterial response. Although a genetic component for caries outcome has been identified, little is known over the genetic aspects underlying its susceptibility. Thus, the aim of this study was to investigate the association between LTF polymorphisms and caries susceptibility. Six hundred seventy seven 12-year-old students were selected: 346 with (DMFT ≥ 1) and 331 without caries experience (DMFT = 0). Also, individuals concentrating higher levels of disease (polarization group, DMFT ≥ 2, n = 253) were tested against those with DMFT ≤ 1 (n = 424). Along with clinical parameters, three representative LTF tag SNPs (rs6441989, rs2073495, rs11716497) were genotyped and the results were evaluated using univariate and multivariate analyses. Allele A for tag SNP rs6441989 was found to be significantly less frequent in the polarization group, conferring a protective effect against caries experience [AA + AG × GG (OR: 0.710, 95% CI: 0.514-0.980, p = 0.045)], and remained significantly associated with caries protection in the presence of gingivitis (p = 0.020) and plaque (p = 0.035). These results might contribute to the understanding of the genetic control of caries susceptibility in humans. PMID:25998152
Carrera, Noa; Arrojo, Manuel; Sanjuán, Julio;
Genome-wide association studies using several hundred thousand anonymous markers present limited statistical power. Alternatively, association studies restricted to common nonsynonymous single nucleotide polymorphisms (nsSNPs) have the advantage of strongly reducing the multiple testing problem...
Fudalej, Sylwia; Ilgen, Mark; Fudalej, Marcin; Kostrzewa, Grazyna; Barry, Kristen; Wojnar, Marcin; Krajewski, Pawel; Blow, Frederic; Ploski, Rafal
The association between suicide and a single nucleotide polymorphism (rs1386483) was examined in the recently identified tryptophan hydroxylase 2 (TPH2) gene. Blood samples of 143 suicide victims and 162 age- and sex-matched controls were examined. The frequency of the TT genotype in the TPH2 polymorphism was higher in suicide victims than in…
Full Text Available The family Loricariidae with about 690 species divided into six subfamilies, is one of the world’s largest fish families. Cytogenetic studies conducted in the family showed that among 90 species analyzed the diploid number ranges from 2n=38 in Ancistrus sp. to 2n=96 in Hemipsilichthys gobio Luetken, 1874. In the present study, fluorescence in situ hybridization (FISH was employed to determine the chromosomal localization of the 18S rDNA gene in four suckermouth armoured catfishes: Kronichthys lacerta (Nichols, 1919, Pareiorhaphis splendens (Bizerril, 1995, Liposarcus multiradiatus (Hancock, 1828 and Hypostomus prope plecostomus (Linnaeus, 1758. All species analyzed showed one chromosome pair with 18S rDNA sequences, as observed in the previous Ag-NORs analyses. The presence of size and numerical polymorphism was observed and discussed, with proposing a hypothesis of the Ag-NOR evolution in Loricariidae.
FUJIMAKI, TETSUO; OGURI, MITSUTOSHI; HORIBE, HIDEKI; KATO, KIMIHIKO; MATSUOKA, REIKO; Abe, Shintaro; TOKORO, FUMITAKA; ARAI, MASAZUMI; Noda, Toshiyuki; WATANABE, SACHIRO; YAMADA, YOSHIJI
Various loci and genes that confer susceptibility to coronary artery disease (CAD) have been identified mainly in Caucasian populations by genome-wide association studies (GWASs). As hypertension is a major risk factor for CAD, certain polymorphisms may contribute to the genetic susceptibility to CAD through affecting the predisposition to hypertension. The aim of the present study was to examine a possible association of hypertension with 29 single-nucleotide polymorphisms (SNPs) previously ...
M. Khoshhal; J. Moradi Haghgoo; Torkzaban, P.; S.R. Arabi; F. Vafaee; M. Hajiloie; B. Pourmoradi
Introduction & Objective: Periodontitis is a multifactorial disease in which host immune system and genetic factors have an important role in its pathogenesis. Genetic polymorphisms in cytokines and their receptors have been proposed as potential markers for periodontal diseases. The aim of the present study was to evaluate whether IL-4R gene polymorphism is associated with chronic periodontitis (CP) or not? Materials & Methods: In this cross sectional study ninety non smoker patients (61 wom...
Full Text Available Background. A positive association between genetic polymorphism and asthma may not be extrapolated from one ethnic group to another based on intra- and interethnic allelic and genotype frequencies differences. Objective. We assessed whether polymorphisms of GST genes (GSTM1, GSTT1, and GSTP1 are associated with asthma and atopy among Tunisian children. Methods. 112 unrelated healthy individuals and 105 asthmatic (73 atopic and 32 nonatopic children were studied. Genotyping the polymorphisms in the GSTT1 and GSTM1 genes was performed using the multiplex PCR. The GSTP1 ILe105Val polymorphism was determined using PCR-RFLP. Results. GSTM1 null genotype was significantly associated with the increased risk of asthma (P=.002. Asthmatic children had a higher prevalence of the GSTP1Ile105 allele than the control group (43.8% and 33.5%, respectively; P=.002. Also, the presence of the GSTP1 homozygote Val/Val was less common in subjects with asthma than in control group. We have found that GSTT1 null genotype (GSTT10Ã¢ÂˆÂ—/0Ã¢ÂˆÂ— was significantly associated with atopy (P=.008. Conclusion. Polymorphisms within genes of the GST superfamily were associated with risk of asthma and atopy in Tunisia.
Sapkota, Bishwa R; Macdonald, Murdo; Berrington, William R; Misch, E Ann; Ranjit, Chaman; Siddiqui, M Ruby; Kaplan, Gilla; Hawn, Thomas R
Although genetic variants in tumor necrosis factor (TNF), mannose binding lectin (MBL), and the vitamin D receptor (VDR) have been associated with leprosy clinical outcomes, these findings have not been extensively validated. We used a case-control study design with 933 patients in Nepal, which included 240 patients with type I reversal reaction (RR), and 124 patients with erythema nodosum leprosum (ENL) reactions. We compared genotype frequencies in 933 cases and 101 controls of seven polymorphisms, including a promoter region variant in TNF (G -308A), three polymorphisms in MBL (C154T, G161A and G170A), and three variants in VDR (FokI, BsmI, and TaqI). We observed an association between TNF -308A and protection from leprosy with an odds ratio of 0.52 (95% confidence interval = 0.29-0.95, p = 0.016). MBL polymorphism G161A was associated with protection from lepromatous leprosy (odds ratio = 0.33, 95% confidence interval = 0.12-0.85, p = 0.010). VDR polymorphisms were not associated with leprosy phenotypes. These results confirm previous findings of an association of TNF -308A with protection from leprosy and MBL polymorphisms with protection from lepromatous leprosy. The statistical significance was modest and will require further study for conclusive validation. PMID:20650301
In thirty cases of resected primary gastric carcinoma, the relative utility of argyrophilic nucleolar organizer regions (AgNORs) staining (single staining) and sequential staining technique using proliferating cell nuclear antigen (PCNA) and AgNORs was studied. The mean number of AgNORs in PCNA-positive cells was significantly larger than that in AgNORs single stained cells. For above two groups, correrating mean number of AgNORs with clinicopathological factors revealed a significant differe...
Fortes, Marina R S; Nguyen, Loan To; Porto Neto, Laercio R; Reverter, Antonio; Moore, Stephen S; Lehnert, Sigrid A; Thomas, Milton G
Puberty onset is a multifactorial process influenced by genetic determinants and environmental conditions, especially nutritional status. Genes, genetic variations, and regulatory networks compose the molecular basis of achieving puberty. In this article, we reviewed the discovery of multiple polymorphisms and genes associated with heifer puberty phenotypes and discuss the opportunities to use this evolving knowledge of genetic determinants for breeding early pubertal Bos indicus-influenced cattle. The discovery of polymorphisms and genes was mainly achieved through candidate gene studies, quantitative trait loci analyses, genome-wide association studies, and recently, global gene expression studies (transcriptome). These studies are recapitulated and summarized in the current review. PMID:27238439
Hummelshoj, T; Bodtger, U; Datta, P;
Several studies indicate genetic involvement of Th2 cytokines in allergic diseases. Interleukin (IL)-13 has been mapped to the cytokine cluster on chromosome 5q31-33, which has been associated with atopic conditions. Recently, an association was reported between the T allele in a promoter...... polymorphism in the IL-13 gene (C to T exchange) at position -1055 and allergic asthma in a population study in the Netherlands. This observation was apparently confirmed in a case-control study using probands and spouses from a Dutch asthma family study, but the polymorphism in that study was reported to...
Burdon, Kathryn P; MacGregor, Stuart; Bykhovskaya, Yelena; Javadiyan, Sharhbanou; Li, Xiaohui; Laurie, Kate J.; Muszynska, Dorota; Lindsay, Richard; Lechner, Judith; Haritunians, Talin; Henders, Anjali K.; Dash, Durga; Siscovick, David; Anand, Seema; Aldave, Anthony
This is a meta-analysis of two genome-wide association studies that found evidence of association of keratoconus with polymorphisms in the promoter of the HGF gene. One polymorphism is associated with higher levels of serum HGF.
Full Text Available Introduction & Objective: Periodontitis is a multifactorial disease in which host immune system and genetic factors have an important role in its pathogenesis. Genetic polymorphisms in cytokines and their receptors have been proposed as potential markers for periodontal diseases. The aim of the present study was to evaluate whether IL-4R gene polymorphism is associated with chronic periodontitis (CP or not? Materials & Methods: In this cross sectional study ninety non smoker patients (61 women and 29 men with chronic periodontitis were selected according to established criteria. They were categorized into three groups according to their clinical attachment level (CAL. Mutation at position 375(alanine/glutamine, 411(leucine/serine, 478(serine/proline, 406 (arginine/ cysteine in the IL-4R gene was detected by a polymerase chain reaction-restriction fragment length polymorphisms (PCR-RFLP method.Results: The distribution of mutations for IL-4 polymorphism at amino acids 375 (P=0.41, 411(P=0.22, 478(P=0.17, 406(P=0.77 were not significantly different among mild, moderate and sever chronic periodontitis patients. Conclusion: This study suggests that there is no correlation between IL-4R polymorphism of chronic periodontitis.(Sci J Hamadan Univ Med Sci 2011;18(3:63-69
Full Text Available Objective: Polymorphism of the size of heterochromatin region of chromosomes has been well documented in human genome and it consists of DNA sequences that are not transcribed. The prime aim of the present study was to evaluate the heterochromatin polymorphism associated with chromosomes in leukemic patients.Materials and Methods: The study was conducted on 35 consecutive leukemic patients and 34 healthy individuals in Modaress and Taleghani hospitals, Tehran, Iran between 2004-2006. By applying Barium Hydroxide saline Giemsa (BSC method with certain alterations, the variant heterochromatin polymorphism of chromosomes 1, 9 and 16 on bone marrow and peripheral blood lymphocyte cultures were evaluated. Chi-square and Fisher’s exact tests were used for statistical analysis with SPSS software.Results: Constitutive heterochromatin polymorphism of chromosomes 1 and 9 in leukemic patients revealed statistical significant differences when compared with chromosomes of healthy controls (p=0.0005 and (p=0.006 respectively. The differences were not significant for chromosome 16, it was 11.4% in leukemic patients and 0% in the control group (p=0.05. The frequency of partial and complete inversions did not show any significant differences between the leukemic patients and the control group.Conclusion: The constitutive heterochromatin polymorphism blocks may provide an opportunity to serve as a marker for the detection and characterization of the chromosomes in leukemic patients.
Chahil, Jagdish Kaur; Munretnam, Khamsigan; Samsudin, Nurulhafizah; Lye, Say Hean; Hashim, Nikman Adli Nor; Ramzi, Nurul Hanis; Velapasamy, Sharmila; Wee, Ler Lian; Alex, Livy
Genome-wide association studies have discovered multiple single nucleotide polymorphisms (SNPs) associated with the risk of common diseases. The objective of this study was to demonstrate the replication of previously published SNPs that showed statistical significance for breast cancer in the Malaysian population. In this case–control study, 80 subjects for each group were recruited from various hospitals in Malaysia. A total of 768 SNPs were genotyped and analyzed to distinguish risk and pr...
Cervical cancer is the most frequent cancer found in Indonesia. The primary treatment of cervical cancer at the locally advanced stage is usually performed by using radiotherapy and chemotherapy. The combination of the two techniques is often called chemoradiotherapy. The response to chemoradiotherapy is influenced by biological and physical factors. Major vault protein (MVP) is a ribonucleoprotein which contributes to drug resistance in some cancers. The purposes of this research were: (1) to determine the correlation between the expression of MVP and the index of p53, including AgNOR values and index of MIB-1; and (2) between MVP and chemoradiotherapy clinical response of cervical cancer. Twenty-one microscopic slides taken from biopsy tissues of cervical cancer patients before undergoing treatment were stained to identify MVP, p53, and MIB-1 by means of immunohistochemistry techniques and AgNORs staining. After undergoing chemoradiotherapy treatment, the patients’ clinical responses were observed by pelvic control method. Experimental results showed that there was a correlation between MVP and AgNOR value (P=0.05), but no correlation between MVP and index of p53 (P=0.729), including MIB-1 LI (P=0.63), in untreated cervical cancer. In addition, there was no association between MVP and chemoradiotherapy response. In conclusion, MVP expression correlates with the process of cell proliferation before the G2 phase of cell cycle in untreated cancer cells. Those have no association with clinical responses after the completion of treatment. (author)
Full Text Available Objective. The aim of this study was to evaluate the association between the Trp64Arg polymorphism in the beta3-adrenergic receptor gene (ADRB3: rs4994 and BMI and serological and anthropometric data in healthy Japanese. Methods. Healthy Japanese recruited in a large-scale integrated manufacturing facility in Japan (=1355; age: 37.25 ± 9.43; BMI: 22.86 ± 3.46 were eligible for analysis. The anthropometric data and serological data were measured during a comprehensive health check, and a self-reporting questionnaire was used to assess lifestyle habits (current exercise, smoking status, alcohol intake, and working style and weight at age 20. Genotyping for the ADRB3 polymorphism was performed by PCR-RFLP method. Results. Among 1355 participants, the genotype frequencies of the Trp/Trp, Trp/Arg, and Arg/Arg variants were 920 (67.9%, 394 (29.1%, and 41 (3.05%, respectively. In the multivariate analysis, a multiple linear regression model in men for the adjustment of age, drinking habits, smoking habits, exercise habits, working status and serological measurements statistically showed an overall weak significance between annual BMI gain from age 20 and age, LDL or ADRB3 polymorphism. Conclusions. The level of LDL, age, and ADRB3 polymorphism (Arg/Arg genotype were statistically associated with annual BMI gain in Japanese men.
Zhu, Guohua; Whyte, Moira K B; Vestbo, Jørgen;
The interleukin 18 receptor (IL18R1) gene is a strong candidate gene for asthma. It has been implicated in the pathophysiology of asthma and maps to an asthma susceptibility locus on chromosome 2q12. The possibility of association between polymorphisms in IL18R1 and asthma was examined by...... genotyping seven SNPs in 294, 342 and 100 families from Denmark, United Kingdom and Norway and conducting family-based association analyses for asthma, atopic asthma and bronchial hyper-reactivity (BHR) phenotypes. Three SNPs in IL18R1 were associated with asthma (0.01131 < or = P < or = 0.01377), five with...... polymorphisms in IL18R1 and asthma....
Minocherhomji, Sheroy; Athalye, Arundhati S; Madon, Prochi F;
To study the association of chromosomal polymorphic variations with infertility and subfertility.......To study the association of chromosomal polymorphic variations with infertility and subfertility....
Pirie, Ailith; Guo, Qi; Kraft, Peter;
INTRODUCTION: Previous studies have identified common germline variants nominally associated with breast cancer survival. These associations have not been widely replicated in further studies. The purpose of this study was to evaluate the association of previously reported SNPs with breast cancer......-specific survival using data from a pooled analysis of eight breast cancer survival genome-wide association studies (GWAS) from the Breast Cancer Association Consortium. METHODS: A literature review was conducted of all previously published associations between common germline variants and three survival outcomes......: breast cancer-specific survival, overall survival and disease-free survival. All associations that reached the nominal significance level of P value <0.05 were included. Single nucleotide polymorphisms that had been previously reported as nominally associated with at least one survival outcome were...
Full Text Available Background: Fine needle aspiration has an important role in diagnosis of thyroid neoplasm. However, it is difficult to differentiate between follicular adenoma and follicular carcinoma by cytology alone. Recently, silver staining has been performed for nucleolar organizer regions (AgNORs to differentiate various tumors. Aims: The present study was undertaken to see if the AgNOR technique could distinguish between benign and malignant lesions, particularly, follicular neoplasm. Materials and Methods: One hundred forty cases of thyroid lesions were examined, which included colloid goiter (n = 36, multinodular goiter (n = 38, subacute thyroiditis (n = 6, Hashimoto′s thyroiditis (n = 17, lymphocytic thyroiditis (n = 3, follicular neoplasm (n = 18, Hurthle cell neoplasm (n = 3, papillary carcinoma (n = 16, and medullary carcinoma (n = 3. Diagnosis was confirmed by histopathology in 80 cases. The usual one-step silver colloidal reaction was performed at room temperature for 35 minutes and intranuclear dots of silver deposits were counted in 100 cells. Results: AgNOR counts of benign and malignant lesions were compared and were found to be statistically significant (P < 0.001. The mean AgNOR counts were higher in neoplastic lesions. Conclusions: AgNOR counting in fine needle aspiration smears is a simple, sensitive, and cost-effective method for differentiating benign from malignant thyroid follicular neoplasms.
Chien, Jason W; Zhang, Xinyi Cindy; Fan, Wenhong; Wang, Hongwei; Zhao, Lue Ping; Martin, Paul J; Storer, Barry E; Boeckh, Michael; Warren, Edus H; Hansen, John A
Candidate genetic associations with acute GVHD (aGVHD) were evaluated with the use of genotyped and imputed single-nucleotide polymorphism data from genome-wide scans of 1298 allogeneic hematopoietic cell transplantation (HCT) donors and recipients. Of 40 previously reported candidate SNPs, 6 were successfully genotyped, and 10 were imputed and passed criteria for analysis. Patient and donor genotypes were assessed for association with grades IIb-IV and III-IV aGVHD, stratified by donor type, in univariate and multivariate allelic, recessive and dominant models. Use of imputed genotypes to replicate previous IL10 associations was validated. Similar to previous publications, the IL6 donor genotype for rs1800795 was associated with a 20%-50% increased risk for grade IIb-IV aGVHD after unrelated HCT in the allelic (adjusted P = .011) and recessive (adjusted P = .0013) models. The donor genotype was associated with a 60% increase in risk for grade III-IV aGVHD after related HCT (adjusted P = .028). Other associations were found for IL2, CTLA4, HPSE, and MTHFR but were inconsistent with original publications. These results illustrate the advantages of using imputed single-nucleotide polymorphism data in genetic analyses and demonstrate the importance of validation in genetic association studies. PMID:22282500
Manchanda, Aastha; Iyengar, Asha R.; Patil, Seema
Background: Anxiety-related traits have been attributed to sequence variability in the genes coding for serotonin transmission in the brain. Two alleles, termed long (L) and short (S) differing by 44 base pairs, are found in a polymorphism identified in the promoter region of serotonin transporter gene. The presence of the short allele and SS and LS genotypes is found to be associated with the reduced expression of this gene decreasing the uptake of serotonin in the brain leading to various anxiety-related traits. Recurrent aphthous stomatitis (RAS) is an oral mucosal disease with varied etiology including the presence of stress, anxiety, and genetic influences. The present study aimed to determine this serotonin transporter gene polymorphism in patients with RAS and compare it with normal individuals. Materials and Methods: This study included 20 subjects with various forms of RAS and 20 normal healthy age- and gender-matched individuals. Desquamated oral mucosal cells were collected for DNA extraction and subjected to polymerase chain reaction for studying insertion/deletion in the 5-HTT gene-linked polymorphic region. Cross tabulations followed by Chi-square tests were performed to compare the significance of findings, P < 0.05 was considered statistically significant. Results: The LS genotype was the most common genotype found in the subjects with aphthous stomatitis (60%) and controls (40%). The total percentage of LS and SS genotypes and the frequency of S allele were found to be higher in the subjects with aphthous stomatitis as compared to the control group although a statistically significant correlation could not be established, P = 0.144 and 0.371, respectively. Conclusion: Within the limitations of this study, occurrence of RAS was not found to be associated with polymorphic promoter region in serotonin transporter gene.
Nikolis, J; Kekic, V
Nucleolus organizing region (NOR) activity in seven probands with Down syndrome due to a de novo (21;21) translocation and their parents was analyzed on the basis of total Ag-NOR size per cell, mean Ag-NOR size per cell (Xc), mean Ag-NOR size per acrocentic (Xa), and the characteristic Ag-NOR number of each subject. The results showed intercellular variations in total Ag-NOR size per cell in all subjects, as well as interindividual variations in mean Ag-NOR size per cell. When the subjects were grouped according to their characteristic Ag-NOR number and the mean Ag-NOR size per cell for each group (GXc) and the mean Ag-NOR size per acrocentric for each group (GXa) were calculated, a number of interesting and significant correlations were found: (1) GXc correlated perfectly with the group's characteristic Ag-NOR number, (2) GXa varied inversely with the group's characteristic Ag-NOR number, and (3) GXc and GXa varied inversely with each other. These results suggest that if the Ag-NOR number of a cell decreases, the total NOR activity of the cell also decreases, but the NOR activity of its chromosomes increases. This finding supports the existence of a compensatory mechanism that regulates NOR activity on the cellular level. PMID:2458214
Haghpanah, S; Nasirabadi, S; Kianmehr, M; Afrasiabi, A; Karimi, M
Sickle cell disease (SCD) is an inherited autosomal recessive disorder. We aimed to describe the spectrum of haplotyes of BS-gene and to investigate a relationship with disease phenotype in patients with SCD in Southern Iran. We didn't find any significant association between BS-globin gene haplotypes and clinical severity of the disease in an Iranian population. The exact mechanism by which the BS-globin gene polymorphism affects clinical presentation is not obvious; however, further detailed studies at the molecular level, with a larger sample size are required to show the mechanisms that influence the clinical presentation of SCD in Iranian population. PMID:22988776
Yoshiki Kuroda; Takahiko Katoh; Takenori Yamauchi; Shouhei Takeuchi
Objective. The aim of this study was to evaluate the association between the Trp64Arg polymorphism in the beta3-adrenergic receptor gene (ADRB3: rs4994) and BMI and serological and anthropometric data in healthy Japanese. Methods. Healthy Japanese recruited in a large-scale integrated manufacturing facility in Japan ( = 1 3 5 5 ; age: 37.25 ± 9.43; BMI: 22.86 ± 3.46) were eligible for analysis. The anthropometric data and serological data were measured during a comprehensive health check, a...
Cheema, Balneek Singh; Iyengar, Sreenivasa; Ahluwalia, Tarun Veer Singh;
genetic polymorphisms in OPN with diabetic nephropathy is lacking. Thus, the present study was designed with the aim to examine the association of an OPN gene promoter polymorphism with diabetic nephropathy in Asian Indians. OPN C-443T (rs11730582) polymorphism was determined in 1115 type 2 diabetic...
Lee, Hwa-Young; Hong, Jin-Pyo; Hwang, Jung-A; Lee, Heon-Jeong; Yoon, Ho-Kyung; Lee, Bun-Hee; Kim, Yong-Ku
Objective The serotonin transporter (5-HTT) genes are major candidate genes for modulating the suicidal behavior. We investigated the association between serotonin transporter polymorphisms and suicidal behavior in patients with major depressive disorder (MDD). Methods Serotonin transporter intron 2 VNTR polymorphism (5-HTTVNTR) and serotonin transporter linked polymorphic region polymorphism (5-HTTLPR) were analyzed in 132 depressed patients with suicidal attempt as well as in 122 normal con...
Watrowski, Rafał; Castillo-Tong, Dan Cacsire; Schuster, Eva; Fischer, Michael B; Speiser, Paul; Zeillinger, Robert
The role of the human epidermal growth factor receptor 2 (HER2) codon 655 (Ile655Val) polymorphism in ovarian cancer is not fully understood. Two studies indicated a possible association between the Val allele and elevated risk or reduced prognosis of ovarian cancer. We investigated the HER2 codon 655 (rs1136201) polymorphism in 242 Austrian women-142 ovarian cancer patients and 100 healthy controls-by polymerase chain reaction and pyrosequencing. Associations between Ile655Val polymorphism and clinicopathological variables (e.g., age, FIGO stage, grading, serous vs. non-serous histology) were evaluated. The genotype distributions in ovarian cancer patients and controls were: AA; 66.2 %, AG; 25.35 %, GG; 8.45 %, and AA; 63 %, AG; 34 %, GG; 3.7 %, respectively (OR 1.15, CI 95 % 0.67-1.96). We observed a non-significant trend toward elevated cancer risk in Val/Val genotype (OR 2.98, CI 95 % 0.82-10.87, p = 0.10). Of note, 11 out of 12 Val/Val homozygotes were postmenopausal. The link between the Val/Val homozygosity and age over 50 years at diagnosis (OR 0.15, CI 95 % 0.02-1.2) was barely significant (p = 0.056). Summarizing, our data indicated a non-significant trend toward increased ovarian cancer risk in the Val/Val homozygosity, especially in women aged above 50 years. Further large-cohort studies focusing on the role of the HER2 codon 655 Val allele are needed. PMID:26666819
Amundsen, S S; Viken, M K; Sollid, L M; Lie, B A
Significant associations between coeliac disease (CD) and single nucleotide polymorphisms (SNPs) distributed over 40 genetic regions have been established. The majority of these SNPs are non-coding and 20 SNPs were, by expression quantitative trait loci (eQTL) analysis, found to harbour cis regulatory potential in peripheral blood mononuclear cells (PBMC). Almost all regions contain genes with an immunological relevant function, of which many act in the same biological pathways. One such pathway is T-cell development in the thymus, a pathway previously not explored in CD pathogenesis. The aim of our study was to explore the regulatory potential of the CD-associated SNPs (n=50) by eQTL analysis in thymic tissue from 42 subjects. In total, 43 nominal significant (PELMO1, rs2074404-NSF (two independent probes) and rs2298428-UBE2L3). When compared across more tissues, we found that 14 eQTLs could represent potentially novel thymus-specific eQTLs. This implies that CD risk polymorphisms could affect gene regulation in thymus. PMID:24871462
McKean-Cowdin, Roberta; Barnholtz-Sloan, Jill; Inskip, Peter D; Ruder, Avima M; Butler, Maryann; Rajaraman, Preetha; Razavi, Pedram; Patoka, Joe; Wiencke, John K; Bondy, Melissa L; Wrensch, Margaret
A pooled analysis was conducted to examine the association between select variants in DNA repair genes and glioblastoma multiforme, the most common and deadliest form of adult brain tumors. Genetic data for approximately 1,000 glioblastoma multiforme cases and 2,000 controls were combined from four centers in the United States that have conducted case-control studies on adult glioblastoma multiforme, including the National Cancer Institute, the National Institute for Occupational Safety and Health, the University of Texas M. D. Anderson Cancer Center, and the University of California at San Francisco. Twelve DNA repair single-nucleotide polymorphisms were selected for investigation in the pilot collaborative project. The C allele of the PARP1 rs1136410 variant was associated with a 20% reduction in risk for glioblastoma multiforme (odds ratio(CT or CC), 0.80; 95% confidence interval, 0.67-0.95). A 44% increase in risk for glioblastoma multiforme was found for individuals homozygous for the G allele of the PRKDC rs7003908 variant (odds ratio(GG), 1.44; 95% confidence interval, 1.13-1.84); there was a statistically significant trend (P = 0.009) with increasing number of G alleles. A significant, protective effect was found when three single-nucleotide polymorphisms (ERCC2 rs13181, ERCC1 rs3212986, and GLTSCR1 rs1035938) located near each other on chromosome 19 were modeled as a haplotype. The most common haplotype (AGC) was associated with a 23% reduction in risk (P = 0.03) compared with all other haplotypes combined. Few studies have reported on the associations between variants in DNA repair genes and brain tumors, and few specifically have examined their impact on glioblastoma multiforme. Our results suggest that common variation in DNA repair genes may be associated with risk for glioblastoma multiforme. PMID:19318434
Ricci, Claudia; Battistini, Stefania; Cozzi, Lorena; Benigni, Michele; Origone, Paola; Verriello, Lorenzo; Lunetta, Christian; Cereda, Cristina; Milani, Pamela; Greco, Giuseppe; Patrosso, Maria Cristina; Causarano, Renzo; Caponnetto, Claudia; Giannini, Fabio; Corbo, Massimo; Penco, Silvana
Paraoxonase (PON) gene polymorphisms have been associated with susceptibility to sporadic amyotrophic lateral sclerosis (ALS). We have investigated the role of the previously associated single nucleotide polymorphisms rs854560, rs662, and rs6954345 in 350 ALS patients and 376 matched controls from Italy. No significant association was observed at genotype and haplotype level. Our data suggest that PON polymorphisms are not involved in ALS pathogenesis in an Italian population. PMID:20381198
Fujimaki, Tetsuo; Oguri, Mitsutoshi; Horibe, Hideki; Kato, Kimihiko; Matsuoka, Reiko; Abe, Shintaro; Tokoro, Fumitaka; Arai, Masazumi; Noda, Toshiyuki; Watanabe, Sachiro; Yamada, Yoshiji
Various loci and genes that confer susceptibility to coronary artery disease (CAD) have been identified mainly in Caucasian populations by genome-wide association studies (GWASs). As hypertension is a major risk factor for CAD, certain polymorphisms may contribute to the genetic susceptibility to CAD through affecting the predisposition to hypertension. The aim of the present study was to examine a possible association of hypertension with 29 single-nucleotide polymorphisms (SNPs) previously identified by meta-analyses of GWASs as susceptibility loci for CAD. Study subjects comprised of 5,460 individuals (3,348 subjects with hypertension and 2,112 controls). The genotypes of SNPs were determined by the multiplex bead-based Luminex assay. The χ(2) test revealed that genotype distributions and allele frequencies for rs12190287 of the transcription factor 21 gene (TCF21) and rs1122608 of the SWI/SNF-related, matrix-associated, actin-dependent regulator of chromatin, subfamily a, member 4 gene (SMARCA4) were significantly (Pindex and smoking status revealed that rs12190287 of TCF21 (P=0.0014; recessive model; odds ratio, 1.21) was significantly associated with hypertension, and the C allele represented a risk factor for this condition. Similar analyses revealed that rs1122608 of SMARCA4 (P=0.0305; dominant model; odds ratio, 0.86), rs9369640 of PHACTR1 (P=0.0119; dominant model; odds ratio, 0.82) and rs599839 of PSRC1 (P=0.0248; dominant model; odds ratio, 0.84) were also related to hypertension, with the minor T, C and G alleles, respectively, being protective against this condition. Thus, the present results indicate that rs12190287 (G→C) of TCF21 is a susceptibility locus for hypertension. PMID:25469260
Kutikhin, Anton G; Ponasenko, Anastasia V; Khutornaya, Maria V; Yuzhalin, Arseniy E; Zhidkova, Irina I; Salakhov, Ramil R; Golovkin, Alexey S; Barbarash, Olga L; Barbarash, Leonid S
Local vascular immune response is primarily initiated via Toll-like receptors (TLRs) and triggering receptor expressed on myeloid cells-1 (TREM-1). We previously showed that certain TLR and TREM-1 gene polymorphisms are associated with coronary artery disease (CAD). Therefore, we hypothesized that these gene polymorphisms are associated with atherosclerosis severity. This study included 292 consecutive patients with CAD who were admitted to the Research Institute for Complex Issues of Cardiovascular Diseases (Kemerovo, Russian Federation) during 2011-2012. Sample genotyping was performed in 96-well format using the TaqMan SNP genotyping assay. We found that C/C genotype of the rs3804099 polymorphism within TLR2 gene and T/T genotype of the rs4711668 polymorphism within TREM-1 gene were significantly associated with severe coronary atherosclerosis while C allele of the rs5743551 polymorphism within TLR1 gene, A/G genotype of the rs4986790 polymorphism and C/T genotype of the rs4986791 polymorphism within TLR4 gene, and C allele of the rs3775073 polymorphism within TLR6 gene were significantly associated with severe noncoronary atherosclerosis. However, A/A genotype of the rs5743810 polymorphism within TLR6 gene was significantly associated with mild noncoronary atherosclerosis. We conclude that certain TLR and TREM-1 gene polymorphisms are significantly associated with atherosclerosis severity in a Russian population. PMID:27200266
Full Text Available Background. PD patients present high incidence of pain with unknown pathogenesis. Objective. We investigated the relation of COMT polymorphisms rs4633 and rs6267 with PD pain. Subjects and Methods. One hundred PD patients and 105 controls were evaluated with simplified Mc GILL pain scale and VAS scale. PD patients were assessed with H&Y grade, UPDRS score, and HAMD scale. Polymorphisms rs4633 and rs6267 were detected by PCR and direct sequencing. Results. Fifty-seven percent of PD patients experienced pain, consisting of PD-related pain (64.91% (the majority was dystonia pain and non-PD-related pain (35.09% (psychogenic pain was most frequent. The frequency of rs6267 genotype “GT/TT” and allele “T” was higher in PD pain. No difference was observed in frequencies of rs4633 between PD pain and without pain. UPDRS and depression score were higher in PD pain. The onset age was earlier in PD-related pain (57.43 ± 19.71 than non-PD-related pain (63.36 ± 6.88. Conclusion. PD patients possess a high prevalence of pain. Dystonia pain was the most frequent type of PD-related pain. COMT gene rs6267 allele “T” associated with PD pain. PD pain was influenced by disease severity and depression. PD onsets earlier in patients with PD-related pain than non-PD-related pain.
Risselada, Arne; Vehof, Jelle; Bruggeman, Richard; Wilffert, Bob; Cohen, Dan; Al Hadithy, Asmar F.; Arends, Johan; Mulder, Hans
Background: Studies have found an association between the ADRA2A 1291 C/G polymorphism and antipsychoticinduced weight gain. A possible association with the metabolic syndrome has not been studied. Objectives: To investigate the association between the ADRA2A 1291 C/G polymorphism and the metabolic
Nishizawa, Daisuke; Ikeda, Kazutaka
Opioids, such as morphine and fentanyl, are widely used as effective analgesics for the treatment of acute and chronic pain. In addition, the opioid system has a key role in the rewarding effects of morphine, ethanol, cocaine and various other drugs. The authors have focused on G-protein-activated inwardly rectifying potassium (GIRK) channel subunits, GIRK2 and GIRK3, which are important molecules in opioid transmission, and found that the SNPs within the GIRK2 and GIRK3 gene region were significantly associated with postoperative analgesic requirements, one of which was also associated with vulnerability to methamphetamine (METH) dependence. Further, by conducting a multistage genome-wide association study (GWAS) in healthy subjects, the authors found that the rs2952768 single-nucleotide polymorphism (SNP) was strongly associated with the requirements for postoperative opioid analgesics after painful cosmetic surgery and consistent results were obtained in patients who underwent abdominal surgery. In addition, the SNP also showed significant association with vulnerability to severe drug dependence in patients with METH dependence, alcohol dependence, and eating disorders and a lower 'Reward Dependence' score on a personality questionnaire in healthy subjects. These outcomes provide valuable information for the personalized treatment of pain and drug dependence. PMID:25069259
Mergen, Hatice; Karaaslan, Cağatay; Mergen, Mehmet; Deniz Ozsoy, Ergi; Ozata, Metin
Obesity is a growing problem and is associated with numerous medical conditions. In several genes coding for molecules involved in the regulation of body weight (fat mass) and thermogenesis, polymorphisms have been reported which possibly modify human obesity risk. The aim of this study was to determine the incidence of the following polymorphisms in the following genes in 262 obese (BMI > or = 30) and 138 control (BMI polymorphism in the 5-HTTLPR and insulin receptor substrate-1 (IRS-1)-Gly972Arg. Our hypothesis was that these polymorphisms would occur more frequently in the obese population. The polymorphisms were determined by polymerase chain reaction (PCR) and restriction genotyping in study population. In our results, no strong associations were observed between BMI status and these polymorphisms. Weak, though significant, association coefficients obtained with HTT and LEPR loci indicate that the genotype numbers at these loci may depend on BMI status to some extent. PMID:17124363
PURPOSE: Polymorphism of the apolipoprotein E (APOE) gene has been associated with dyslipidemia and cardiovascular disease. This study examines the association of APOE polymorphisms and diabetic retinopathy. DESIGN: Population-based cross-sectional study. METHODS: We studied 1,398 people aged 49 to ...
Kusche, Henrik; Elmer, Kathryn R.; Meyer, Axel
Background Color polymorphisms are a conspicuous feature of many species and a way to address broad ecological and evolutionary questions. Three potential major evolutionary fates of color polymorphisms are conceivable over time: maintenance, loss, or speciation. However, the understanding of color polymorphisms and their evolutionary implications is frequently impaired by sex-linkage of coloration, unknown inheritance patterns, difficulties in phenotypic characterization, and a lack of evolu...
Arslan, A.; Yorulmaz, T.; Toyran, K.; Albayrak, I.; Zima, Jan
Roč. 76, č. 4 (2012), s. 435-439. ISSN 0025-1461 Institutional support: RVO:68081766 Keywords : AgNOR staining * C-banding * cytogenetics * jerboas Subject RIV: EG - Zoology Impact factor: 0.809, year: 2012
Two functional single nucleotide polymorphisms (SNPs) in the 5,10-methylenetetrahydrofolate reductase (MTHFR) gene, C677T and A1298C, lead to decreased enzyme activity and affect chemosensitivity of tumor cells. We investigated whether these MTHFR SNPs were associated with breast cancer survival in African-American and Caucasian women. African-American (n = 143) and Caucasian (n = 105) women, who had incident breast cancer with surgery, were recruited between 1993 and 2003 from the greater Baltimore area, Maryland, USA. Kaplan-Meier survival and multivariate Cox proportional hazards regression analyses were used to examine the relationship between MTHFR SNPs and disease-specific survival. We observed opposite effects of the MTHFR polymorphisms A1298C and C677T on breast cancer survival. Carriers of the variant allele at codon 1298 (A/C or C/C) had reduced survival when compared to homozygous carriers of the common A allele [Hazard ratio (HR) = 2.05; 95% confidence interval (CI), 1.05–4.00]. In contrast, breast cancer patients with the variant allele at codon 677 (C/T or T/T) had improved survival, albeit not statistically significant, when compared to individuals with the common C/C genotype (HR = 0.65; 95% CI, 0.31–1.35). The effects were stronger in patients with estrogen receptor-negative tumors (HR = 2.70; 95% CI, 1.17–6.23 for A/C or C/C versus A/A at codon 1298; HR = 0.36; 95% CI, 0.12–1.04 for C/T or T/T versus C/C at codon 677). Interactions between the two MTHFR genotypes and race/ethnicity on breast cancer survival were also observed (A1298C, pinteraction = 0.088; C677T, pinteraction = 0.026). We found that the MTHFR SNPs, C677T and A1298C, were associated with breast cancer survival. The variant alleles had opposite effects on disease outcome in the study population. Race/ethnicity modified the association between the two SNPs and breast cancer survival
Full Text Available Abstract Background Cerebral malaria is one of the most severe manifestations of Plasmodium falciparum malaria. The sequestration of parasitized red blood cells (PRBCs to brain microvascular endothelium has been shown to contribute to the pathophysiology of cerebral malaria. Recent studies reported increased levels of von Willebrand factor (VWF and reduced activity of VWF-cleaving protease, ADAMTS13 (a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13, in patients with cerebral malaria. Methods Association of six single nucleotide polymorphisms (SNPs of the ADAMTS13 gene with cerebral malaria was examined in 708 Thai patients with P. falciparum malaria. Results Among six SNPs, the derived allele of a SNP located in intron 28, rs4962153-A, was significantly associated with protection against cerebral malaria when 115 cerebral malaria patients were compared with 367 mild malaria patients (Fisher's exact P-value = 0.0057; OR = 0.27; 95% CI = 0.096-0.76. Significant association was also detected between 115 cerebral malaria and 593 non-cerebral malaria (226 non-cerebral severe malaria and 367 mild malaria patients (Fisher's exact P-value = 0.012; OR = 0.30; 95% CI = 0.11-0.83. Conclusions Excessive adhesion of PRBCs to the platelet-decorated ultra-large VWF (ULVWF appears to enhance the sequestration of PRBCs to cerebral microvascular endothelium. The genetic association observed in the present study implies that the regulation of platelet-decorated ULVWF strings by ADAMTS13 may play a role in the development of cerebral malaria.
Günther, Lukas; Hufnagl, Peter
A new staining method for dual demonstration of Estrogen receptors (ER) and argyrophilc Nucleolus‐Organizer Regions (AgNORs) was developed. To rule out possible reciprocal effects, serial slides of 10 invasive ductale breast cancers were stained with either the single staining method or the simultaneous ER/AgNOR‐staining method and investigated comparatively. By measuring the slides with the image analysis system AMBA, reciprocal effects could be excluded. It was proven that dual staining of ...
The effect of apatite nanoparticles on proliferation potential and biological behaviour of the human hepatocellular carcinoma in vitro were investigated. After the treatment of Bel- 7402 hepatocellular carcinoma cells with apatite nanoparticles at a concentration of 5 × 10-4 mmol/ L for 4days, Feulgen and AgNOR stain were conducted and the specimens were observed by microscope. The DNA and AgNOR were quantified with image analysis techniques. It was found that there was a significant decrease of the DNA content (58.62 ± 6.52) in the nanoparticles treated group compared to the control (78.21 ± 4.17). It was further found that there was a decrease in the number of AgNOR granules in the nanoparticle treated group (7.41 ± 1.02) compared to the control group (9.95± 0.28). The experimental results showed that apatite nanoparticles could decrease the DNA reproductive activity and the rRNA synthesis in Bel-7402 hepatocellular carcinoma cells.
Full Text Available Previous observational studies investigating the association between methylenetetrahydrofolate reductase (MTHFR polymorphisms and acute myeloid leukemia risk (AML have yielded inconsistent results. The aim of this study is to derive a more precise estimation of the association between MTHFR (C677T and A1298C polymorphisms and acute myeloid leukemia risk. PubMed and Embase databases were systematically searched to identify relevant studies from their inception to August 2013. Odds ratios (ORs with 95% confidence intervals (CIs were the metric of choice. Thirteen studies were selected for C677T polymorphism (1838 cases and 5318 controls and 9 studies (1335 patients and 4295 controls for A1298C polymorphism. Overall, pooled results showed that C677T polymorphism was not significant associated with AML risk(OR, 0.98-1.04; 95% CI, 0.86-0.92 to 1.09-1.25. Similar results were observed for the A1298C polymorphism and in subgroup analysis. All comparisons revealed no substantial heterogeneity nor did we detect evidence of publication bias. In summary, this meta-analysis provides evidence that MTHFR polymorphisms were not associated with AML risk. Further investigations are needed to offer better insight into the role of these polymorphisms in AML carcinogenesis.
The receptor activator of NF-κB (RANK), its ligand (RANKL) and osteoprotegerin (OPG) have been reported to play a role in the pathophysiological bone turnover and in the pathogenesis of breast cancer. Based on this we investigated the role of single nucleotide polymorphisms (SNPs) within RANK, RANKL and OPG and their possible association to breast cancer risk. Genomic DNA was obtained from Caucasian participants consisting of 307 female breast cancer patients and 396 gender-matched healthy controls. We studied seven SNPs in the genes of OPG (rs3102735, rs2073618), RANK (rs1805034, rs35211496) and RANKL (rs9533156, rs2277438, rs1054016) using TaqMan genotyping assays. Statistical analyses were performed using the χ2-tests for 2 x 2 and 2 x 3 tables. The allelic frequencies (OR: 1.508 CI: 1.127-2.018, p=0.006) and the genotype distribution (p=0.019) of the OPG SNP rs3102735 differed significantly between breast cancer patients and healthy controls. The minor allele C and the corresponding homo- and heterozygous genotypes are more common in breast cancer patients (minor allele C: 18.4% vs. 13.0%; genotype CC: 3.3% vs. 1.3%; genotype CT: 30.3% vs. 23.5%). No significantly changed risk was detected in the other investigated SNPs. Additional analysis showed significant differences when comparing patients with invasive vs. non-invasive tumors (OPG rs2073618) as well as in terms of tumor localization (RANK rs35211496) and body mass index (RANKL rs9533156 and rs1054016). This is the first study reporting a significant association of the SNP rs3102735 (OPG) with the susceptibility to develop breast cancer in the Caucasian population
Hwang, Dae Woo; Kim, Ki Tack; Lee, Sang Hoon; Kim, Jung Youn; Kim, Dong Hwan
Background Degenerative lumbar scoliosis (DLS) progresses with aging after 50-60 years, and the genetic association of DLS remains largely unclear. In this study, the genetic association between collagen type II alpha 1 (COL2A1) gene and DLS was investigated. Methods COL2A1 gene polymorphism was investigated in DLS subjects compared to healthy controls to investigate the possibility of its association with COL2A1 gene. Based on a single nucleotide polymorphism (SNP) database, SNP (rs2276454) ...
Lee, Peter J
single nucleotide polymorphisms (SNPs) in the genes for catecholamine-O-methyltransferase (COMT), μ-opioid receptor and GTP cyclohydrolase (GCH1) have been linked to acute and chronic pain states. COMT polymorphisms are associated with experimental pain sensitivity and a chronic pain state. No such association has been identified perioperatively. We carried out a prospective observational clinical trial to examine associations between these parameters and the development of postoperative pain in patients undergoing third molar (M3) extraction.
Objective: To investigate the genetic association between polymorphism of mdm2 gene and symptoms and pathological types of non-small cell lung cancer (NSCLC). Methods: Polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) was used to identify mdm2 genotypes. The Pearson Chi square test and Woolf statistic method were used to analyze the relative risk and 95% confidence interval (CI) in order to find the genetic association between polymorphism of mdm2 gene and symptoms and pathological types of NSCLC. Results: In the SNP rs1196337 (a G to A base change) AA genotype showed association with cough of NSCLC (P<0.05). Conclusion: The polymorphism of mdm2 gene may be associated with symptom as cough of NSCLC. (authors)
Vares, Maria; Saetre, Peter; Deng, Hong;
Different lines of evidence indicate that methylenetetrahydrofolate reductase (MTHFR) functional gene polymorphisms, causative in aberrant folate-homocysteine metabolism, are associated with increased vulnerability to several heritable developmental disorders. Opposing views are expressed...
Ye, Feng; Cheng, Qi; Hu, Yuting; Jing ZHANG; Chen, Huaizeng
PARP-1 is a nuclear enzyme that plays an important role in DNA repair, recombination, proliferation and the genome stability. The PARP-1 Val762Ala polymorphism has been associated with increased risk of developing cancers of the prostate, esophagus and lung. The aim of this study was to determine whether the PARP-1 Val762Ala polymorphism is associated with the risk of cervical carcinoma. MA-PCR was used to genotype the PARP-1 Val762Ala polymorphism in 539 women with cervical carcinoma, 480 wo...
Wu, Xue-qing; Xu, Su-ming; Liu, Jun-fen; Bi, Xing-yu; Wu, Yuan-xia; Liu, Jing
Purpose Polycystic ovary syndrome (PCOS) is a common endocrine disorder disease among women in reproductive-age. Since follicle stimulating hormone (FSH) exerts important biological functions, the association between PCOS and FSH receptor (FSHR) polymorphisms attracts wide attention. The aim of this study was to evaluate whether polymorphisms of FSHR at 307 and 680 codons are associated with PCOS patients in China. Methods Patients with PCOS (n = 215) and controls (n = 205) were recruited fro...
Zuhong Lu; Yunfei Bai; Xiaoyan Ke; Beili Sun; Lu Cheng; Pengfeng Xiao; Qinyu Ge
Single nucleotide polymorphisms (SNPs) are important markers which can be used in association studies searching for susceptible genes of complex diseases. High-throughput methods are needed for SNP genotyping in a large number of samples. In this study, we applied polyacrylamide gel-based microarray combined with dual-color hybridization for association study of four BDNF polymorphisms with autism. All the SNPs in both patients and controls could be analyzed quickly and correctly. Among four ...
Karolina Maria Burghardt; Vishal Avinashi; Christina Kosar; Wei Xu; Wales, Paul W.; Yaron Avitzur; Aleixo Muise
Recently, genetic associations have been described in intestinal transplants. Namely, Crohn's disease susceptibility gene NOD2 polymorphisms have been reported to be more prevalent in patients with graft failure following intestinal transplantation (IT). Therefore, we sought to determine if polymorphisms in the NOD2 signaling cascade, including NOD2, CARD9, RAC1 and ATG16L1 are associated with intestinal failure (IF) or its complications. We carried out a cross-sectional study of 59 children ...
Full Text Available Lanlan He,1,* Yong Wang2,* 1Emergency Department, Zhenjiang First People’s Hospital, Zhenjiang, People’s Republic of China; 2Department of Interventional Radiology and Vascular Surgery, Zhongda Hospital, Southeast University, Nanjing, Jiangsu, People’s Republic of China *Both authors contributed equally to this work Purpose: Several molecular epidemiological studies have investigated the association between OPN rs11730582 C>T polymorphism and cancer risk, but the results are inconsistent. Hence, a meta-analysis was conducted to determine the association of this polymorphism with cancer risk. Materials and methods: The related articles were searched in PubMed, Embase, and Chinese National Knowledge Infrastructure databases. Pooled odds ratios and 95% confidence intervals were calculated to evaluate the strength of the associations. A random-effects model or fixed-effects model was employed depending on the heterogeneity. Results: A total of ten case-control studies involving 2,749 cancer cases and 3,398 controls were included in the meta-analysis. In overall analysis, OPN rs11730582 C>T polymorphism was not associated with cancer risk. In a stratified analysis by cancer type, no significant association was found between OPN rs11730582 C>T polymorphism and the risk of glioma, gastric cancer, and other cancers. Conclusion: This meta-analysis suggests that OPN rs11730582 C>T polymorphism is not associated with cancer susceptibility. Keywords: osteopontin, polymorphism, cancer, risk
Husted, L B; Harsløf, T; Stenkjær, L; Carstens, M; Jørgensen, N R; Langdahl, Bente Lomholt
UNLABELLED: The P2X(7) receptor is an ATP-gated cation channel. We investigated the effect of both loss-of-function and gain-of-function polymorphisms in the P2X(7) receptor gene on BMD and risk of vertebral fractures and found that five polymorphisms and haplotypes containing three of these...... investigate the effect of these polymorphisms on BMD and risk of vertebral fractures in a case-control study including 798 individuals. METHODS: Genotyping was carried out using TaqMan assays. BMD was measured using dual energy X-ray absorptiometry, and vertebral fractures were assessed by lateral spinal X...... polymorphisms were associated with BMD and fracture risk. INTRODUCTION: The P2X(7) receptor is an ATP-gated cation channel. P2X(7) receptor knockout mice have reduced total bone mineral content, and because several functional polymorphisms have been identified in the human P2X(7) receptor gene, we wanted to...
Lan, Yan; WEI, CHUAN-DONG; Chen, Wen-Cheng; Wang, Jun-Li; Wang, Chun-Fang; Pan, Guo-Gang; Wei, Ye-Sheng; Nong, Le-Gen
Purpose Although the polymorphisms of erythrocyte complement receptor type 1 (CR1) in patients with malaria have been extensively studied, a question of whether the polymorphisms of CR1 are associated with severe malaria remains controversial. Furthermore, no study has examined the association of CR1 polymorphisms with malaria in Chinese population. Therefore, we investigated the relationship of CR1 gene polymorphism and malaria in Chinese population. Materials and Methods We analyzed polymor...
Full Text Available Tuberculosis (TB is a major cause of morbidity and mortality worldwide. IRGM1 is an important protein in the innate immune response against intracellular pathogens by regulating autophagy. Polymorphisms in the IRGM genes are known to influence expression levels and may be associated with outcome of infections. This case-control study was done on 150 patients with PTB and 150 healthy subjects to determine whether the IRGM polymorphisms at positions −1208 A/G (rs4958842, −1161 C/T (rs4958843, and −947 C/T (rs4958846 were associated with PTB. The polymorphisms were determined using tetra-amplification refractory mutation system-PCR (T-ARMS-PCR. The results showed that the IRGM −1161 C/T and −947 C/T polymorphisms were associated with decreased susceptibility to PTB (OR = 0.06, 95% CI = 0.03–0.13, P < 0.001 and OR = 0.27; 95% CI = 0.013–0.55, P < 0.001, resp.. No significant difference was found among the groups regarding −1208 A/G polymorphism. In conclusion we found that the IRGM −1161 C/T and −947 C/T polymorphisms but not −1208 A/G polymorphism provide relative protection against PTB in a sample of Iranian population.
Nissen, Nis; Madsen, Jonna Skov; Bladbjerg, Else-Marie;
neck was measured using a Hologic QDR-2000 densitometer and femoral neck axis length, neck width, neck shaft angle, and femoral head diameter were measured from the screen images. Genotype frequencies were compatible with Hardy-Weinberg equilibrium. No significant differences between homozygotes for...... geometric dimensions of the proximal femur in perimenopausal women are not associated with the MTHFR c.677C > T, P2X(7) (Glu496Ala), P2X(7) (Ile568Asn), and LRP5 exon 9 (c.266A > G) polymorphisms....
Hummelshoj, T; Bødtger, Uffe; Datta, P; Malling, H J; Oturai, A; Poulsen, L K; Ryder, L P; Sorensen, P S; Svejgaard, E; Svejgaard, A
occur at position -1111. In the present study, we established that this polymorphism is located at position -1024 relative to the ATG translation initiation codon, and investigated whether it confers a genetic predisposition to atopic conditions and the Th1 condition multiple sclerosis (MS) in Caucasian...
Full Text Available Abstract Background Marbling score (MS is the major quantitative trait that affects carcass quality in beef cattle. In this study, we examined the association between genetic polymorphisms of the micromolar calcium-activated neutral protease gene (micro-calpain, CAPN1 and carcass traits in Korean cattle (also known as Hanwoo. Results By direct DNA sequencing in 24 unrelated Korean cattle, we identified 39 sequence variants within exons and their flanking regions in CAPN1. Among them, 12 common polymorphic sites were selected for genotyping in the beef cattle (n = 421. Statistical analysis revealed that a polymorphism in the 3'UTR (c.2151*479C>T showed significant association with MS (Pcor. = 0.02. Conclusion Our findings suggest that polymorphisms in CAPN1 might be one of the important genetic factors involved in carcass quality in beef cattle, although it could be false positive association.
Full Text Available Background: Vitiligo or leukoderma is a chronic skin condition that causes loss of pigment due to destruction of melanocytes, resulting in irregular pale patches of skin. Vitiligo is a polygenic disease and is associated with autoimmunity with an unknown etiology. Aims: One of the candidate genes which has a strong association with several autoimmune diseases is ctla0 -4 gene located in chromosome 2q33 region. We investigated the possible association between ctla0 -4 gene polymorphism in exon 1 (A49G and vitiligo in patients from South India and compared the distribution of this polymorphism to matched control groups. Patients and Methods: The polymorphism was detected by Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP method in 175 patients and 180 normal, age/ethnicity matched individuals. Consistency of genotype frequencies with the Hardy-Weinberg equilibrium was tested using a ÷2 test. Results: There was no significant difference between the genotype (P=0.93 and allele (P=0 .615 frequencies of CTLA-4 A49G polymorphism in patients and normal healthy individuals. However there was significant association of the CTLA-4 genotype ( P=0.02 and allelic frequency ( P=0.008 between the segmental and non-segmental sub groups within vitiligo. Conclusion: Our results indicate that there is no association between CTLA-4 A49G gene polymorphism and vitiligo in southern Indian population.
Balamurugan, S.; Sugapriya, D.; Shanthi, P.; Thilaka, V.; Venkatadesilalu, S.; Pushpa, V.; Madhavan, M.
The multidrug resistance 1 (MDR1) gene product, P-glycoprotein (Pgp/p170) is a membrane protein, which acts as an ATP dependant efflux pump that expels a wide variety of organic compounds including chemotherapeutic agents from the cell. Pgp over expression has been demonstrated to be linked with poor treatment outcome and poor prognosis in a number of malignant tumors. AgNORs is a simple, reliable and inexpensive method of evaluating the proliferative activity of a tumor. We have studied MDR1...
Full Text Available Abstract Background Non-synonymous polymorphisms within the prion protein gene (PRNP influence the susceptibility and incubation time for transmissible spongiform encephalopathies (TSE in some species such as sheep and humans. In cattle, none of the known polymorphisms within the PRNP coding region has a major influence on susceptibility to bovine spongiform encephalopathy (BSE. Recently, however, we demonstrated an association between susceptibility to BSE and a 23 bp insertion/deletion (indel polymorphism and a 12 bp indel polymorphism within the putative PRNP promoter region using 43 German BSE cases and 48 German control cattle. The objective of this study was to extend this work by including a larger number of BSE cases and control cattle of German and Swiss origin. Results Allele, genotype and haplotype frequencies of the two indel polymorphisms were determined in 449 BSE cattle and 431 unaffected cattle from Switzerland and Germany including all 43 German BSE and 16 German control animals from the original study. When breeds with similar allele and genotype distributions were compared, the 23 bp indel polymorphism again showed a significant association with susceptibility to BSE. However, some additional breed-specific allele and genotype distributions were identified, mainly related to the Brown breeds. Conclusion Our study corroborated earlier findings that polymorphisms in the PRNP promoter region have an influence on susceptibility to BSE. However, breed-specific differences exist that need to be accounted for when analyzing such data.
Itaka, Toshio; Agemizu, Kenichiro; Aruga, Seiji; Machida, Shuichi
Itaka, T, Agemizu, K, Aruga, S, and Machida, S. G allele of the IGF2 ApaI polymorphism is associated with judo status. J Strength Cond Res 30(7): 2043-2048, 2016-Previous studies have reported that the insulin-like growth factor 2 (IGF2) ApaI polymorphism is associated with body mass index, fat mass, and grip strength. Competitive judo requires high levels of strength and power. The purpose of this study was to investigate the association between the IGF2 ApaI and ACTN3 R577X polymorphisms and judo status. The subjects were 156 male judo athletes from a top-level university in Japan. They were divided into 3 groups based on their competitive history: international-level athletes, national-level athletes, and others. Genomic DNA was extracted from the saliva of each athlete, and the maximal isometric strength of the trunk muscles and handgrip strength were measured. Genotyping by polymerase chain reaction-restriction fragment length polymorphism was used to detect IGF2 (rs680) and α-actinin-3 (ACTN3) (rs1815739) gene polymorphisms. The genotype frequencies of the 2 gene polymorphisms were compared among the 3 groups of judo athletes and controls. International-level judo athletes showed a higher frequency of the GG + GA genotype of the IGF2 gene than that of the national-level athletes and others. There was an inverse linear correlation between the frequency of the IGF2 AA genotype and level of judo performance (p = 0.041). Back muscle strength relative to height and weight was higher in subjects with the GG + GA genotype than in those with the AA genotype. Conversely, the ACTN3 R577X polymorphism was not associated with judo status. Additionally, no differences were found in back muscle or handgrip strength among the ACTN3 genotypes. In conclusion, the results indicate that the IGF2 gene polymorphism may be associated with judo status. PMID:26677828
Stanton, Sasha E; Ward, Maureen M.; Christos, Paul; Sanford, Rachel; Lam, Christina; Cobham, Marta V; Donovan, Diana; Scheff, Ronald J; Cigler, Tessa; Moore, Anne; Vahdat, Linda T.; Lane, Maureen E.; Chuang, Ellen
Background Variations in single nucleotide polymorphisms (SNPs) have been associated with enhanced drug efficacy and toxicity in cancer therapy. SNP variations in the ErbB2 gene have been identified that alter the protein sequence of the HER2-neu protein, but how these polymorphisms affect prognosis and response to HER2 targeted therapy is unknown. We examined eleven ErbB2 SNPs that alter the HER2-neu amino acid sequence to determine whether any of these particular polymorphisms were associat...
Omrani, Mir Davood; Bazargani, Soroush; Bagheri, Morteza; Yazdan-nejad, Hamed
BACKGROUND: A single nucleotide variation within catechol-o-methyl transferase (COMT) gene may alter the COMT enzyme activity level. Polymorphism of Val158Met in the COMT gene has been related to malignancy. In this regard, a study was carried out to find a possible association between the COMT gene polymorphism in patients with sporadic prostate cancer (PCa) and benign prostatic hyperplasia (BPH). METHODS: All types of COMT158 Val/Met polymorphism were carried out using ASO-PCR method in 41 ...
Vares, Maria; Saetre, Peter; Deng, Hong; Cai, Guiqing; Liu, Xiehe; Hansen, Thomas; Rasmussen, Henrik B; Werge, Thomas; Melle, Ingrid; Djurovic, Srdjan; Andreassen, Ole A; Agartz, Ingrid; Hall, Håkan; Terenius, Lars; Jönsson, Erik G
Different lines of evidence indicate that methylenetetrahydrofolate reductase (MTHFR) functional gene polymorphisms, causative in aberrant folate-homocysteine metabolism, are associated with increased vulnerability to several heritable developmental disorders. Opposing views are expressed...... considering the possible association between MTHFR and susceptibility for schizophrenia. In order to evaluate if age of onset could explain some of this discrepancy we investigated the relationship between two functional MTHFR gene polymorphisms and age at onset in this disorder. Scandinavian patients (n...... = 820) diagnosed with schizophrenia, schizoaffective disorder, and schizophreniform disorder were investigated. Two functional MTHFR single nucleotide polymorphisms (SNPs; rs1801131 and rs1801133) were genotyped and the effect of MTHFR polymorphisms on the age of onset was examined with survival...
Katherine Y King
Full Text Available An ancestral polymorphic allele of the human autophagy-related gene IRGM1 is associated with altered gene expression and a genetic risk for Crohn's Disease (CD. We used the single nucleotide polymorphism rs10065172C/T as a marker of this polymorphic allele and genotyped 370 African American and 177 Caucasian tuberculosis (TB cases and 180 African American and 110 Caucasian controls. Among African Americans, the TB cases were more likely to carry the CD-related T allele of rs10065172 (odds ratio of 1.54; 95% confidence interval, 1.17-2.02; P<0.01 compared to controls. Our finding suggests that this CD-related IRGM1 polymorphic allele is also associated with human susceptibility to TB disease among African Americans.
Full Text Available Preeclampsia (PE is a pregnancy-specific disorder that results in maternal mortality and morbidity. Growing evidence indicated that cytokines are involved in the pathogenesis of PE and interleukin-4 VNTR polymorphism could be implicated in altering the PE risk. The aim of this study was to evaluate the possible association between IL-4 VNTR polymorphism and susceptibility to PE in Iranian population for the first time. Genetic polymorphism was evaluated in 192 PE and 186 healthy control women by polymerase chain reaction method. We found that the VNTR polymorphism of IL-4 gene has significantly increased the risk of preeclampsia (RP2/RP1 versus RP1/RP1, OR, 2.8 [95% CI, 1.7 to 8.8]; P=0.0001 and RP2/RP2 versus RP1/RP1; P=0.002. The results showed that carriage of IL-4 VNTR RP2 allele has positive association with preeclampsia susceptibility.
Šrám, Radim; Binková, Blanka; Dejmek, Jan; Chvátalová, Irena; Solanský, I.; Topinka, Jan
Roč. 608, - (2006), s. 121-128. ISSN 1383-5718 R&D Projects: GA MŽP SL/5/160/05; GA MŽP SL/740/5/03; GA MŽP(CZ) SI/340/2/00 Institutional research plan: CEZ:AV0Z50390512 Keywords : pregnancy outcomes * birth weight * genetic polymorphism Subject RIV: DN - Health Impact of the Environment Quality Impact factor: 2.122, year: 2006
Bergman, O.; Åhs, F; Furmark, T; Appel, L; Linnman, C; Faria, V; Bani, M; Pich, E M; Bettica, P; Henningsson, S; Manuck, S B; Ferrell, R E; Nikolova, Y S; Hariri, A R; Fredrikson, M.
Essential for detection of relevant external stimuli and for fear processing, the amygdala is under modulatory influence of dopamine (DA). The DA transporter (DAT) is of fundamental importance for the regulation of DA transmission by mediating reuptake inactivation of extracellular DA. This study examined if a common functional variable number tandem repeat polymorphism in the 3′ untranslated region of the DAT gene (SLC6A3) influences amygdala function during the processing of aversive emotio...
Zhang, Wenchao; Wang, Hui; Zhang, Wei [Key Laboratory of Cardiovascular Remodeling and Function Research Chinese Ministry of Education and Chinese Ministry of Public Health, Qilu Hospital of Shandong University, Jinan (China); Lv, Ruijuan [Department of Emergency, Qilu Hospital of Shandong University, Jinan (China); Wang, Zhihao [Key Laboratory of Cardiovascular Remodeling and Function Research Chinese Ministry of Education and Chinese Ministry of Public Health, Qilu Hospital of Shandong University, Jinan (China); Department of Geriatrics, Qilu Hospital of Shandong University, Jinan (China); Shang, Yuanyuan; Zhang, Yun; Zhong, Ming [Key Laboratory of Cardiovascular Remodeling and Function Research Chinese Ministry of Education and Chinese Ministry of Public Health, Qilu Hospital of Shandong University, Jinan (China); Chen, Yuguo; Tang, Mengxiong, E-mail: email@example.com [Key Laboratory of Cardiovascular Remodeling and Function Research Chinese Ministry of Education and Chinese Ministry of Public Health, Qilu Hospital of Shandong University, Jinan (China); Department of Emergency, Qilu Hospital of Shandong University, Jinan (China)
Activin receptor-like kinase 7 (ALK7) is a type I receptor for the TGF-β superfamily and has recently been demonstrated to play an important role in the maintenance of metabolic homeostasis. To investigate the association of the ALK7 gene polymorphism with metabolic syndrome (MetS) and cardiovascular remodeling in MetS patients. The single nucleotide polymorphism rs13010956 in the ALK7 gene was genotyped in 351 Chinese subjects undergoing carotid and cardiac ultrasonography. The associations of the ALK7 gene polymorphism with the MetS phenotype, MetS parameters, and cardiovascular ultrasonic features were analyzed. The rs13010956 polymorphism in the ALK7 gene was found to be significantly associated with the MetS phenotype in females (p < 0.05) and was also significantly associated with blood pressure in the total (p < 0.05) and female populations (p < 0.01). Further analysis revealed that rs13010956 was associated with mean intima-media thickness of the carotid arteries in females (p < 0.05). After control for body mass index, blood pressure, fasting blood glucose, and triglycerides, rs13010956 was also found to be significantly associated with left ventricular mass index in the total (p < 0.05) and female populations (p < 0.05). Our findings suggested that the ALK7 gene polymorphism rs13010956 was significantly associated with MetS risk in females and may be involved in cardiovascular remodeling in MetS patients.
Activin receptor-like kinase 7 (ALK7) is a type I receptor for the TGF-β superfamily and has recently been demonstrated to play an important role in the maintenance of metabolic homeostasis. To investigate the association of the ALK7 gene polymorphism with metabolic syndrome (MetS) and cardiovascular remodeling in MetS patients. The single nucleotide polymorphism rs13010956 in the ALK7 gene was genotyped in 351 Chinese subjects undergoing carotid and cardiac ultrasonography. The associations of the ALK7 gene polymorphism with the MetS phenotype, MetS parameters, and cardiovascular ultrasonic features were analyzed. The rs13010956 polymorphism in the ALK7 gene was found to be significantly associated with the MetS phenotype in females (p < 0.05) and was also significantly associated with blood pressure in the total (p < 0.05) and female populations (p < 0.01). Further analysis revealed that rs13010956 was associated with mean intima-media thickness of the carotid arteries in females (p < 0.05). After control for body mass index, blood pressure, fasting blood glucose, and triglycerides, rs13010956 was also found to be significantly associated with left ventricular mass index in the total (p < 0.05) and female populations (p < 0.05). Our findings suggested that the ALK7 gene polymorphism rs13010956 was significantly associated with MetS risk in females and may be involved in cardiovascular remodeling in MetS patients
Habibi, Manijeh; Naderi, Nosratllah; Farnood, Alma; Balaii, Hedieh; Dadaei, Tahereh; Almasi, Shohreh; Zojaji, Homayoun; Asadzadeh Aghdae, Hamid; Zali, Mohammad Reza
Aim: The present study evaluated the association between G241R and K469E polymorphisms of intercellular adhesion molecule 1 gene and inflammatory bowel disease in Iranian population. Background: Inflammatory bowel disease including ulcerative colitis and Crohn’s disease, is a chronic idiopathic inflammatory disease of the gastrointestinal tract. There are two single base polymorphisms of intercellular adhesion molecule 1gene, G241R and K469E, reported to be associated with inflammatory disorders. Patients and methods: In this case-control study, 156 inflammatory bowel disease patients (110 ulcerative colitis and 46 Crohn’s disease patients) and 131 healthy controls were enrolled. Two polymorphisms of intercellular adhesion molecule 1 gene, including G241R and K469E, were assessed by polymerase chain reaction followed by restriction fragment length polymorphism. Results: The E469 allele of K469E polymorphism was significantly more frequent in Crohn’s disease patients compared to controls (P< 0.05, OR= 1.83; 95% CI: 1.13 to 2.96). The mutant homozygote genotype of K469E polymorphism (E/E) was also significantly more frequent in Crohn’s disease patients compared to controls (P< 0.05, OR= 4.23; 95% CI: 1.42 to 12.59). No difference was observed in the frequency of K469E polymorphism among ulcerative colitis patients compared to controls. There were no significant differences in genotype and allele frequencies of G241R polymorphism among ulcerative colitis and Crohn’s disease patients compared to control subjects. Conclusion: According to our findings, K469E polymorphism of intercellular adhesion molecule 1 gene may probably participate in the pathogenesis of Crohn’s disease in Iran. PMID:27099667
Atherosclerosis Is A Complex Multifocal Arterial Disease Involving Interactions Of Multiple Genetic And Environmental Factors. Advances In Techniques Of Molecular Genetics Have Revealed That Genetic Polymorphisms Significantly Influence Susceptibility To Atherosclerotic Vascular Diseases. A Large Number Of Candidate Genes, Genetic Polymorphisms And Susceptibility Loci Associated With Atherosclerotic Diseases Have Been Identified In Recent Years And Their Number Is Rapidly Increasing ....
Objective To investigate the association of single nucleotide polymorphisms(SNPs)of the mannan-binding lectin(MBL)gene with serum levels,development,progression and prognosis of severe lupus nephritis(LN).Methods A total of 107 severe lupus nephritis patients were enrolled in the study from January 2003 to October2013.Integrated capillary electrophoresis was used to detect MBL gene polymorphism in peripheral blood
Molvarec, Attila; Vér, Agota; Fekete, Andrea; Rosta, Klára; Derzbach, László; Derzsy, Zoltán; Karádi, István; Rigó, János
Associations have been reported between estrogen receptor alpha (ESR1) gene polymorphisms and various pathological conditions, including cardiovascular diseases. Our aim was to investigate whether two polymorphisms of the ESR1 gene (ESR1 c.454 -397T>C: PvuII restriction site and c.454 -351A>G: XbaI restriction site) are associated with preeclampsia. In a case-control study, we analyzed blood samples from 119 severely preeclamptic patients and 103 normotensive, healthy pregnant women using the polymerase chain reaction (PCR)-restriction fragment length polymorphism (RFLP) method. All of the women were Caucasian. There was no association between severe preeclampsia and the PvuII and XbaI ESR1 gene polymorphisms separately. However, with the simultaneous carriage of both polymorphisms, the TT/AA genotype combination was significantly more frequent in severely preeclamptic patients than in healthy control subjects (24.4% vs. 9.7%, p=0.003), whereas the TT/AG combination was significantly less frequent in the severely preeclamptic group than in the control group (5.0% vs. 18.4%, p=0.002). According to the haplotype estimation, the homozygous T-A haplotype carriers had an increased risk of severe preeclampsia independent of maternal age, prepregnancy BMI, primiparity and smoking status (adjusted odds ratio [OR]: 4.36, 95% confidence interval [CI]: 1.65-11.53). The GG genotype of the XbaI polymorphism was associated with a lower risk of fetal growth restriction in patients with severe preeclampsia (OR: 0.23, 95% CI: 0.07-0.73). In conclusion, the homozygous T-A haplotype carriers of ESR1 PvuII and XbaI polymorphisms showed an increased risk of severe preeclampsia. In addition, the GG genotype of the XbaI polymorphism decreased the risk of fetal growth restriction in severely preeclamptic patients. PMID:17510501
Miwa Sasaki; Shigeru Sakano; Naoko Okayama; Jumpei Akao; Tomohiko Hara; Yoshihisa Kawai; Chietaka Ohmi; Yuji Hinoda; Katsusuke Naito
Upper urinary tract transitional cell carcinoma (UUT-TCC) is quite an uncommon disease, and its prognosis differs among individuals irrespective of tumor stage. DNA repair gene polymorphisms are reported to result in the modulation of the repair capacity and might influence the prognosis of UUT-TCC. We examined the associations between functional polymorphisms in five DNA repair genes, and the prognosis of UUT-TCC in 103 UUT-TCC patients. Variant alleles in xeroderma pigmentosum complementati...
Christiane Montag; Eva-Maria Brockmann; Anja Lehmann; Müller, Daniel J.; Dan Rujescu; Jürgen Gallinat
The nonapeptide oxytocin (OXT) and its receptor (OXTR) have been implicated in social cognition, empathy, emotion and stress regulation in humans. Previous studies reported associations between OXT and OXTR genetic polymorphisms and risk for disorders characterized by impaired socio-emotional functioning, such as schizophrenia and autism. Here we investigate the influence of two single nucleotide polymorphisms (SNPs) within the OXTR gene on a measure of socio-emotional functioning in schizoph...
Kaulfers, Anne-Marie; Deka, Ranjan; Dolan, Lawrence; Martin, Lisa J.
Background Dyslipidemia and overweight are common issues in children. Identifying genetic markers of risk could lead to targeted interventions. A polymorphism of SNP rs7566605 near insulin-induced gene 2 (INSIG2) has been identified as a strong candidate gene for obesity, through its feedback control of lipid synthesis. Objective To identify polymorphisms in INSIG2 which are associated with overweight (BMI ≥ 85% for age) and dyslipidemia in children. Hypothesis: The C allele of rs7566605 woul...
Wang, Ying; Yin, Ji-Ye; Li, Xiang-ping; Chen, Juan; Qian, Chen-yue; Zheng, Yi; Fu, Yi-Lan; Chen, Zi-Yu; Zhou, Hong-Hao; Liu, Zhao-Qian
Lung cancer is one of the most common cancers and is the leading cause of death worldwide. Platinum-based chemotherapy is the main treatment method in lung cancer patients. Our previous studies indicated that single nucleotide polymorphisms (SNPs) in some transporter genes played important role in platinum-based chemotherapy efficacy. The aim of this study was to investigate the association of SNPs in transporter genes and platinum-based chemotherapy efficacy. The main polymorphisms on transp...
Han, Dong Hee; KIM, SU KANG; Kang, Sungwook; Choe, Bong-Keun; Kim, Keon Sik; Chung, Joo-Ho
The aim of this study was to determine whether single nucleotide polymorphisms (SNPs) of matrix metallopeptidase 2 (MMP2) are associated with obesity. MMP2 is an enzyme with proteolytic activity against matrix and nonmatrix proteins, particularly basement membrane constituents. To identify the relationship between polymorphisms of MMP2 and overweight/obese, we genotyped 5 SNPs (rs17242319, rs1053605, rs243849, rs2287074, and rs10775332) of the coding region of MMP2 using the Golden Gate assay...
Hoth, Karin F.; Paul, Robert H.; Williams, Leanne M.; Dobson-Stone, Carol; Todd, Elizabeth; Schofield, Peter R.; Gunstad, John; Cohen, Ronald A.; Gordon, Evian
Efforts to identify genetic factors that confer an increased risk for the expression of psychiatric symptoms have focused on polymorphisms in variety of candidate genes, including the catechol-O-methyltransferase (COMT) gene. Results from previous studies that have examined associations between the functional COMT polymorphism (Val158Met) and mental health have been mixed. In the present study, we examined the relationships between COMT, early life stress, and personality in a healthy adult s...
Full Text Available AIM: To explore the association between genetic polymorphisms of the receptor for advanced glycation end-products (RAGE and susceptibility, chemotherapy response rate and prognosis of non-small cell lung cancer (NSCLC. METHOD: This is a prospective study in which 562 patients with NSCLC and 764 healthy controls were enrolled. Three RAGE genetic polymorphisms, namely, -429T/C, -374T/A and 82G/S were genotyped. Platinum-based chemotherapy was given to 432 subjects with advanced inoperable NSCLC and their responses to chemotherapy were evaluated. RESULTS: All the polymorphic genotypes of RAGE polymorphisms were associated with susceptibility for NSCLC. Only the 82G/S polymorphisms denoted a significant difference between responders and non-responders to chemotherapy. The 82SS genotype and 82S allele distribution not only increased the NSCLC risk, but also was associated with a lower chemotherapy response rate and poor prognosis, indicated by overall survival and progression free survival. CONCLUSION: The 82G/S genetic polymorphism of RAGE gene might be used as a genetic marker to screen for patients sensitive to thermotherapy and to predict the prognosis of NSCLC.
Leonardo, Daniela P.; Albuquerque, Dulcinéia M.; Lanaro, Carolina; Baptista, Letícia C.; Cecatti, José G.; Surita, Fernanda G.; Parpinelli, Mary A.; Costa, Fernando F.; Franco-Penteado, Carla F.; Fertrin, Kleber Y.; Costa, Maria Laura
Background Preeclampsia is one of the leading causes of maternal and neonatal morbidity and mortality in the world, but its appearance is still unpredictable and its pathophysiology has not been entirely elucidated. Genetic studies have associated single nucleotide polymorphisms in genes encoding nitric oxide synthase and matrix metalloproteases with preeclampsia, but the results are largely inconclusive across different populations. Objectives To investigate the association of single nucleotide polymorphisms (SNPs) in NOS3 (G894T, T-786C, and a variable number of tandem repetitions VNTR in intron 4), MMP2 (C-1306T), and MMP9 (C-1562T) genes with preeclampsia in patients from Southeastern Brazil. Methods This prospective case-control study enrolled 77 women with preeclampsia and 266 control pregnant women. Clinical data were collected to assess risk factors and the presence of severe complications, such as eclampsia and HELLP (hemolysis, elevated liver enzymes, and low platelets) syndrome. Results We found a significant association between the single nucleotide polymorphism NOS3 T-786C and preeclampsia, independently from age, height, weight, or the other SNPs studied, and no association was found with the other polymorphisms. Age and history of preeclampsia were also identified as risk factors. The presence of at least one polymorphic allele for NOS3 T-786C was also associated with the occurrence of eclampsia or HELLP syndrome among preeclamptic women. Conclusions Our data support that the NOS3 T-786C SNP is associated with preeclampsia and the severity of its complications. PMID:26317342
Daniela P Leonardo
Full Text Available Preeclampsia is one of the leading causes of maternal and neonatal morbidity and mortality in the world, but its appearance is still unpredictable and its pathophysiology has not been entirely elucidated. Genetic studies have associated single nucleotide polymorphisms in genes encoding nitric oxide synthase and matrix metalloproteases with preeclampsia, but the results are largely inconclusive across different populations.To investigate the association of single nucleotide polymorphisms (SNPs in NOS3 (G894T, T-786C, and a variable number of tandem repetitions VNTR in intron 4, MMP2 (C-1306T, and MMP9 (C-1562T genes with preeclampsia in patients from Southeastern Brazil.This prospective case-control study enrolled 77 women with preeclampsia and 266 control pregnant women. Clinical data were collected to assess risk factors and the presence of severe complications, such as eclampsia and HELLP (hemolysis, elevated liver enzymes, and low platelets syndrome.We found a significant association between the single nucleotide polymorphism NOS3 T-786C and preeclampsia, independently from age, height, weight, or the other SNPs studied, and no association was found with the other polymorphisms. Age and history of preeclampsia were also identified as risk factors. The presence of at least one polymorphic allele for NOS3 T-786C was also associated with the occurrence of eclampsia or HELLP syndrome among preeclamptic women.Our data support that the NOS3 T-786C SNP is associated with preeclampsia and the severity of its complications.
Shiotani, Akiko; Fujita, Yoshihiko; Nishio, Kazuto
The risk of gastrointestinal (GI) bleeding is increased in association with the use of low-dose aspirin (LDA). There are few studies of the association between genetic polymorphisms and the risks of aspirin-induced ulcer or its complications. Individuals with two single nucleotide polymorphisms (SNPs) of cyclooxygenase-1 (COX-1), A-842G and C50T, exhibit increased sensitivity to aspirin and lower prostaglandin synthesis capacity but the polymorphism lacked statistical significance in relation to an association with bleeding peptic ulcer. In our previous Japanese study, SLCO1B1 521TT genotype and the SLCO1B1 *1b haplotype were significantly associated with the risk of peptic ulcer and ulcer bleeding in patients taking LDA, especially in the patients with angiotensin converting enzyme inhibitor (ACEI), angiotensin type 1 receptor blocker (ARB), or statin co-treatment. Protonpump inhibitors (PPIs) are recommended for patients who require antiplatelet therapy and have a history of upper GI bleeding. The interaction between PPIs and consequent impaired effectiveness of clopidogrel has caused concern regarding the effect of genetic polymorphisms of the CYP2C19 which mediates conversion of clopidogrel to its active metabolite. The later recent genome-wide analysis of SNPs indicated the association of several SNPs with small bowel bleeding in Japanese patients taking LDA. The data are still lacking and further prospective studies are needed to identify the specific gene polymorphisms as risk or protective factors for GI bleeding associated with LDA. PMID:26369686
Zhu, G; Vestbo, J; Lenney, W;
The prostanoid DP receptor (PTGDR) is shown to be involved in the asthma patho-physiology and the results from the published genetic association studies are inconsistent. Four single nucleotide polymorphisms (SNPs) in PTGDR were genotyped in 342 and 294 families from UK and Denmark respectively....... Asthma and asthma-related phenotypes were analyzed using family-based association analyses. In the UK families, a promoter polymorphism (-731A/G) showed significant associations with asthma (P=0.0022), atopic asthma (P=0.0044), bronchial hyperreactivity or BHR (P=0.00120) and strict asthma (P=0.......0008). The P-values for asthma, BHR and strict asthma were significant even after the most stringent correction for the number of markers and the number of phenotypes analyzed (<0.0031). An intronic polymorphism (+6651C/T) also showed significant associations with asthma (P=0.0302), atopic asthma (P=0...
Full Text Available Fibroblast growth factor receptor 4 (FGFR4 polymorphisms are positively correlated with tumor progression in numerous malignant tumors. However, the association between FGFR4 genetic variants and the risk of hepatocellular carcinoma (HCC has not yet been determined. In this study, we investigated the potential associations of FGFR4 single nucleotide polymorphisms (SNPs with HCC susceptibility and its clinicopathological characteristics.Four SNPs in FGFR4 (rs1966265, rs351855, rs2011077, and rs7708357 were analyzed among 884 participants, including 595 controls and 289 patients with HCC. The samples were further analyzed to clarify the associations between these gene polymorphisms and the risk of HCC, and the impact of these SNPs on the susceptibility and clinicopathological characteristics of HCC. After adjusting for other covariants, HCC patients who carrying at least one A genotype (GA and AA at rs351855 were observed to have a higher risk of liver cirrhosis compared with those carrying the wild-type genotype (GG (OR: 2.113, 95% CI: 1.188-3.831. Moreover, the patients with at least one A genotype were particularly showed a high level of alpha-fetoprotein (AFP.Our findings suggest that genetic polymorphism in FGFR4 rs351855 may be associated with the risk of HCC coupled with liver cirrhosis and may markedly increase the AFP level in Taiwanese patients with HCC. In addition, this is the first study that evaluated the risk factors associated with FGFR4 polymorphism variants in Taiwanese patients with HCC.
Liu, Yangbo; Li, Liangda; Shi, Shanfen; Chen, Xin; Gao, Jianqing; Zhu, Minyu; Yuan, Jiandong
The susceptibility loci of ERAP1 polymorphisms have been found to be strongly associated with ankylosing spondylitis (AS). The researches in multiple ethnic cohorts suggested that the population attributable risk in ERAP1 polymorphisms is at a high significance level. This study was undertaken to estimate the prevalence and incidence of subsets of AS and investigate the specific variants of ERAP1 polymorphisms in AS susceptibility, in the Han ethnic Chinese population in Zhejiang Province. AS patients were selected, diagnosed, and confirmed by a qualified rheumatologist. The basal clinical and demographic characteristics were compared with all subjects. Genotypes for eight selected single nucleotide polymorphisms (SNPs) in ERAP1 gene (rs27038, rs27037, rs27434, rs27980, rs7711564, rs30187, rs10050860, and rs17482078) were determined by using the Sequenom MassARRAY iPLEX platform in Zhejiang Han Chinese population. Association analyses were performed on the whole genotyped data set in 707 unrelated ankylosing spondylitis cases and 837 ethnically matched controls. We observed the strongest association between AS and HLA-B27, which confers over 90 % of ankylosing spondylitis cases. Moreover, we found three loci of ERAP1 polymorphisms were at a high significance level (rs27037 P = 0.00451; rs27434 P = 0.00012; rs27980 P = 0.00682) with AS in Zhejiang population. We also confirmed polymorphism locus of ERAP1 previously reported association with AS (rs27434; P = 5.3 × 10(-12)). Our results indicated a difference in the mechanism of susceptibility loci in subsets of Zhejiang Han Chinese population and provided further evidence that rs27434 is the key polymorphism associated with AS in ERAP1 gene. PMID:26350268
Coppedè, Fabio; Migheli, Francesca; Lo Gerfo, Annalisa; Fabbrizi, Maria Rita; Carlesi, Cecilia; Mancuso, Michelangelo; Corti, Stefania; Mezzina, Nicoletta; del Bo, Roberto; Comi, Giacomo P; Siciliano, Gabriele; Migliore, Lucia
The aim of the present study was to investigate the possible contribution of three common functional polymorphisms in the DNA repair protein X-ray repair cross-complementing group 1 (XRCC1), namely Arg194Trp (rs1799782), Arg280His (rs25489) and Arg399Gln (rs25487), to sporadic amyotrophic lateral sclerosis (SALS). We genotyped 206 Italian SALS patients and 203 matched controls for XRCC1 Arg194Trp, Arg280His and Arg399Gln polymorphisms by means of PCR/RFLP technique, searching for association between any of the studied polymorphisms and disease risk, age and site of onset. We observed a statistically significant difference in XRCC1 Gln399 allele frequencies between SALS cases and controls (0.39/0.28; p=0.001). The present study suggests that the XRCC1 Arg399Gln polymorphism might contribute to SALS risk. PMID:19707910
Medica, Igor; Ostojic, Sasa; Pereza, Nina; Kastrin, Andrej; Peterlin, Borut
A meta-analysis of association studies was performed to assess whether the reported genetic polymorphisms in cytokine genes are risk factors for recurrent miscarriage (RM). The electronic PubMed database was searched for case-control studies on immunity-related genes in RM. Investigations of a single polymorphism/gene involvement in RM reported more than five times were selected. Aggregating data from seven case-control studies on -308/tumour necrosis factor-alpha polymorphism, the odds ratio (OR) for RM was 1.1 (0.87-1.39) if the polymorphism was considered under a dominant genetic model. In six studies on -1082/interleukin-10 (IL-10) polymorphism, the OR under a dominant model was 0.76 (0.58-0.99), and under a recessive model the OR was 0.90 (0.71-1.15). In five case-control studies on -174/IL-6 polymorphism, the OR for RM under a recessive model was 1.29 (0.69-2.40). The results show a statistically significant association with RM for the -1082/IL-10 genotype. PMID:19778488
Bergman, O; Åhs, F; Furmark, T; Appel, L; Linnman, C; Faria, V; Bani, M; Pich, E M; Bettica, P; Henningsson, S; Manuck, S B; Ferrell, R E; Nikolova, Y S; Hariri, A R; Fredrikson, M; Westberg, L; Eriksson, E
Essential for detection of relevant external stimuli and for fear processing, the amygdala is under modulatory influence of dopamine (DA). The DA transporter (DAT) is of fundamental importance for the regulation of DA transmission by mediating reuptake inactivation of extracellular DA. This study examined if a common functional variable number tandem repeat polymorphism in the 3' untranslated region of the DAT gene (SLC6A3) influences amygdala function during the processing of aversive emotional stimuli. Amygdala reactivity was examined by comparing regional cerebral blood flow, measured with positron emission tomography and [(15)O]water, during exposure to angry and neutral faces, respectively, in a Swedish sample comprising 32 patients with social anxiety disorder and 17 healthy volunteers. In a separate US sample, comprising 85 healthy volunteers studied with blood oxygen level-dependent functional magnetic resonance imaging, amygdala reactivity was assessed by comparing the activity during exposure to threatening faces and neutral geometric shapes, respectively. In both the Swedish and the US sample, 9-repeat carriers displayed higher amygdala reactivity than 10-repeat homozygotes. The results suggest that this polymorphism contributes to individual variability in amygdala reactivity. PMID:25093598
D Nageswara Rao
Full Text Available Background : CYP3A5 was observed to be an important genetic contributor to inter individual differences in CYP3A-dependent drug metabolism in acute leukemic patients. Loss of CYP3A5 expression was mainly conferred by a single nucleotide polymorphism at 6986A>G (CYP3A5FNx013. We investigated the association between CYP3A5FNx013 polymorphism and acute leukemia. Materials and Methods : Two hundred and eighty nine acute leukemia cases comprising of 145 acute lymphocytic leukemia (ALL, 144 acute myeloid leukemia and 241 control samples were analyzed for CYP3A5FNx013 polymorphism using PCR-RFLP method. Statistical analysis was performed with SPSS version (15.0 to detect the association between CYP3A5FNx013 polymorphism and acute leukemia. Results : The CYP3A5FNx013 polymorphism 3/3 genotype was significantly associated with acute leukemia development (χ2 - 133.53; df-2, P 0.000. When the data was analyzed with respect to clinical variables, mean WBC, blast % and LDH levels were increased in both ALL and AML cases with 3/3 genotype. The epidemiological variables did not contribute to the genotype risk to develop either AML or ALL. Conclusion : The results suggest that the CYP3A5FNx013 polymorphism might confer the risk to develop ALL or AML emphasizing the significance of effective phase I detoxification in carcinogenesis. Association of the polymorphism with clinical variables indicate that the 3/3 genotype might also contribute to poorer survival of the patients.
Akanksha N Thakkar
Full Text Available Background: Genetic polymorphisms of CYP2C9 can lead to wide inter-individual variations in drug metabolism. Decreased metabolism leads to higher plasma levels, causing adverse drug reactions (ADRs. Polymorphic alleles CYP2C9 FNx01 2 and CYP2C9 FNx01 3 occur in the Indian population and this may serve as the basis for using genotyping as a tool to predict phenytoin toxicity. Aims: To evaluate the association between the presence of polymorphic alleles CYP2C9 FNx01 2 and FNx013 and phenytoin toxicity in Indian patients with epilepsy. Settings and Design: A case-control study with cases defined as those who had plasma phenytoin concentrations above 20 μg/ml. Materials and Methods: The study population included 259 patients with epilepsy on phenytoin. Phenotyping was done using High Performance Liquid Chromatography. Those with plasma phenytoin levels above 20 μg/ml were taken as cases and the rest as controls. Genotyping was done by Polymerase Chain Reaction - Restriction Fragment Length Polymorphism. Statistics: Numerical data between groups was compared using unpaired-′t′ test. Between-group comparison of categorical data was done using Chi square for trend with crude odds ratio (OR. Adjusted OR was calculated using binary logistic regression. Results: There were 40 cases and 219 controls. Mean phenytoin dosage between groups was not statistically significant. Of the 40 cases, 25 (62.5% cases had wild alleles versus 178 (81.3% controls. We found a significant association between polymorphic alleles CYP2C9 FNx01 2 and FNx013 and toxic phenytoin levels. After adjusting for age, sex and dose, a significant association between polymorphic alleles and phenytoin toxicity was still found. Conclusions: This study shows significant association between polymorphic alleles and phenytoin toxicity in this study population. However, until technology for genotyping becomes cost-effective, we would recommend Therapeutic Drug Monitoring to guide dosing.
Full Text Available Abstract Background Recent research has implicated that mutations in the neurexin-1 (NRXN1 gene on chromosome 2p16.3 might play a role in schizophrenia, autism, and nicotine dependence. In order to explore the association of NRXN1 polymorphisms with schizophrenia, we made a case-control association study in Chinese Han population. Methods We examined six tag single nucleotide polymorphisms (SNPs spanning 116.7 kb of NRXN1 in 768 schizophrenic patients and 738 healthy control subjects. The association of NRXN1 polymorphisms with schizophrenia and the age-at-onset of this disease were explored. Results Our results showed that four SNPs of NRXN1 gene were significantly associated with schizophrenia (rs10490168: G > A, p = 0.017; rs2024513: A > G, p = 0.006; rs13382584: T > C, p = 0.009; and rs1558852: G > A, p = 0.031. Furthermore, the association of SNP rs2024513 with schizophrenia remained significance after the Bonferroni correction. Haplotypes consisting of above six SNPs also showed significantly associated with schizophrenia (global chi-square = 14.725, p = 0.022. A protective haplotype AGTGCA remained associated with schizophrenia, even after 10,000 permutation tests (empirical p-value = 0.043. However, we did not find any association with age-at-onset of schizophrenia with NRXN1 polymorphisms. Conclusions Our findings suggest that NRXN1 might represent a major susceptibility gene for schizophrenia in Chinese Han population.
Jeffrey A Canter
Full Text Available The objective of this study was to determine if MTND2*LHON4917G (4917G, a specific non-synonymous polymorphism in the mitochondrial genome previously associated with neurodegenerative phenotypes, is associated with increased risk for age-related macular degeneration (AMD. A preliminary study of 393 individuals (293 cases and 100 controls ascertained at Vanderbilt revealed an increased occurrence of 4917G in cases compared to controls (15.4% vs.9.0%, p = 0.11. Since there was a significant age difference between cases and controls in this initial analysis, we extended the study by selecting Caucasian pairs matched at the exact age at examination. From the 1547 individuals in the Vanderbilt/Duke AMD population association study (including 157 in the preliminary study, we were able to match 560 (280 cases and 280 unaffected on exact age at examination. This study population was genotyped for 4917G plus specific AMD-associated nuclear genome polymorphisms in CFH, LOC387715 and ApoE. Following adjustment for the listed nuclear genome polymorphisms, 4917G independently predicts the presence of AMD (OR = 2.16, 95%CI 1.20-3.91, p = 0.01. In conclusion, a specific mitochondrial polymorphism previously implicated in other neurodegenerative phenotypes (4917G appears to convey risk for AMD independent of recently discovered nuclear DNA polymorphisms.
The suggestion that there is a connection between chronic intraprostatic inflammation and prostate cancer was declared some years ago. As Toll-like receptors (TLRs) are the key players in the processes of chronic intraprostatic inflammation, there is a hypothesis that TLR gene polymorphisms may be associated with prostate cancer risk. Although a number of comprehensive studies have been conducted on large samples in various countries, reliable connections between these single nucleotide polymorphisms and prostate cancer risk, stage, grade, aggressiveness, ability to metastasize, and mortality have not been detected. Results have also varied slightly in different populations. The data obtained regarding the absence of connection between the polymorphisms of the genes encoding interleukin-1 receptor-associated kinases (IRAK1 and IRAK4) and prostate cancer risk might indicate a lack of association between inherited variation in the TLR signaling pathway and prostate cancer risk. It is possible to consider that polymorphisms of genes encoding TLRs and proteins of the TLR pathway also do not play a major role in the etiology and pathogenesis of prostate cancer. Feasibly, it would be better to focus research on associations between TLR single nucleotide polymorphisms and cancer risk in other infection-related cancer types
Full Text Available Background & objectives: The Vitamin-D receptor (VDR regulates vitamin D levels and calcium metabolism in the body and these are known to be associated with endocrine dysfunctions, insulin resistance and type-2 diabetes in polycystic ovarian syndrome (PCOS. Studies on VDR polymorphisms among PCOS women are sparse. We undertook this study to investigate the association pattern of VDR polymorphisms (Cdx2, Fok1, Apa1 and Taq1 with PCOS among Indian women. Methods: For the present study, 250 women with PCOS and 250 normal healthy control women were selected from Hyderabad city, Telangana, India. The four VDR polymorphisms were genotyped and analysed using ASM-PCR (allele specific multiple PCR and PCR-RFLP (restriction fragment length polymorphism. Results: The genotype and allele frequency distributions of only Cdx2 showed significant difference between the PCOS cases and control women, indicating protective role of this SNP against PCOS phenotype. However, significant association was observed between VDR genotypes and some of the PCOS specific clinical/biochemical traits. For example, Fok1 showed a significant genotypic difference for the presence of infertility and Cdx2 genotpes showed association with testosterone levels. Further, the two haplotypes, ACCA and ACTA, were found to be significantly associated with PCOS indicating haplotype specific risk. Interpretation & conclusions: Although VDR polymorphisms have not shown significant association with PCOS, in view of functional significance of the SNPs considered, one cannot yet rule out the possibility of their association with PCOS. Further, specifically designed studies on large cohorts are required to conclusively establish the role of VDR polymorphisms in PCOS, particularly including data on vitamin D levels.
Ivens, A.B.F.; Kronauer, Daniel Jan Christoph; Boomsma, J.J.
Twenty-six polymorphic microsatellite loci were developed for four species of ant-associated root-aphids: Geoica utricularia, Forda marginata, Tetraneura ulmi and Anoecia corni. We found up to 9 alleles per locus, with an average of 4.8. We also report polymorphic cross-amplification of eleven of...... these markers between different pairs of study species. Furthermore, we tested previously published aphid microsatellites and found one locus developed for Pemphigus bursarius to be polymorphic in G. utricularia. These microsatellite markers will be useful to study the population structure of aphids...... associated with the ant Lasius flavus and possibly other ants. Such studies are relevant because: 1. L. flavus mounds and their associated flora and fauna are often key components in protected temperate grasslands, and 2. L. flavus and its diverse community of root-aphids provide an interesting model system...
LING-LING XU; HONG-DING XIANG; CHANG-CHUN QIU; QUN XU
Objective To investigate the association of ghrelin gene polymorphisms with metabolic syndrome in Han Nationality Chinese. Methods A total of 240 patients with metabolic syndrome annd 427 adults aged above forty years were recruited. Genotypes were determined by polymerase chain reaction and restriction fragment lengthpolymorphism analysis.Results The allelic frequency of the Leu72Met polymorphismwas 17.3% in the patient group and 11.9% in the control group(x2=7.36, P=0.007). Metabolic syndrome was more prevalent among carriers of the Met72 variant (43.8 vs 33.1%, age- and sex-adjusted odds ratio=1.57, P=0.01). No Arg51Gln variants were found in our study subjects. Conclusion Rather than being associated with its individual components, Leu72Met polymorphism is associated with metabolic syndrome in the Han Nationality Chinese. Arg51Gln polymorphism is rare in the Hart Nationality Chinese.
Chemoradiotherapy is one of treatments for the locally advanced cervical cancer given by concurrent radiotherapy combined with chemotherapy in the same time. Chemoradiotherapy response is influenced by biological factor i.e. cell kinetic that consists of cell proliferation and death. In this research, the correlation between AgNOR, MIB-1 cell proliferation biomarker and the expression of apoptotic caspase-3 with chemoradiotherapy response of cervical cancer has been studied. Twenty one microscopic tissue samples were taken from cervical cancer biopsies before radiotherapy. The tissue samples were stained with AgNOR, whereas MIB-1 and apoptosis caspase-3 in the tissue samples were detected by immunochemistry technique. After the completion of chemoradiotherapy treatment, the clinical response was observed by pelvic control method. The result of this research show that there is no correlation between AgNOR, MIB-1 value with apoptosis (p>0.05) before chemoradiotherapy. Cell proliferation observed by AgNOR and MIB-1 before chemoradiotherapy indicate no correlation with chemoradiotherapy response, however the apoptotic expression shows positive correlation with chemoradiotherapy response. The index of caspase-3 apoptosis obtained from this research can be used for considering the chemoradiotherapy schedule for the cervical cancer patient. (author)
Fábio M. Corregiari
Full Text Available OBJECTIVES: Approximately 40-60% of obsessive-compulsive disorder patients are nonresponsive to serotonin reuptake inhibitors. Genetic markers associated with treatment response remain largely unknown. We aimed (1 to investigate a possible association of serotonergic polymorphisms in obsessive-compulsive disorder patients and therapeutic response to selective serotonin reuptake inhibitors and (2 to examine the relationship between these polymorphisms and endocrine response to intravenous citalopram challenge in responders and non-responders to serotonin reuptake inhibitors and in healthy volunteers. METHODS: Patients with obsessive-compulsive disorder were classified as either responders or non-responders after long-term treatment with serotonin reuptake inhibitors, and both groups were compared with a control group of healthy volunteers. The investigated genetic markers were the G861C polymorphism of the serotonin receptor 1Dβ gene and the T102C and C516T polymorphisms of the serotonin receptor subtype 2A gene. RESULTS: The T allele of the serotonin receptor subtype 2A T102C polymorphism was more frequent among obsessive-compulsive disorder patients (responders and non-responders than in the controls (p<0.01. The CC genotype of the serotonin receptor subtype 2A C516T polymorphism was more frequent among the non-responders than in the responders (p<0.01. The CC genotype of the serotonin receptor subtype 1Dβ G681C polymorphism was associated with higher cortisol and prolactin responses to citalopram (p<0.01 and p<0.001, respectively and with a higher platelet-rich plasma serotonin concentration among the controls (p<0.05. However, this pattern was not observed in the non-responders with the same CC genotype after chronic treatment with serotonin reuptake inhibitors. This CC homozygosity was not observed in the responders.
Full Text Available BACKGROUND: Two polymorphisms, -260C/T and -651C/T, in the CD14 gene have been implicated in susceptibility to cancer. However, the results remain inconclusive. This meta-analysis aimed to investigate the association between the two polymorphisms and risk of cancer. METHODS: All eligible case-control studies published up to March 2014 were identified by searching PubMed, Web of Science, CNKI and WanFang database. Pooled odds ratio (OR with 95% confidence interval (CI were used to access the strength of this association in fixed- or random-effects model. RESULTS: 17 case-control studies from fourteen articles were included. Of those, there were 17 studies (4198 cases and 4194 controls for -260C/T polymorphism and three studies (832 cases and 1190 controls for -651C/T polymorphism. Overall, no significant associations between the two polymorphisms of CD14 gene and cancer risk were found. When stratified by ethnicity, cancer type and source of control, similar results were observed among them. In addition, in further subgroups analysis by Helicobacter pylori (H. pylori infection status and tumor location in gastric cancer subgroup, we found that the CD14 -260C/T polymorphism may increase the risk of gastric cancer in H. pylori-infected individuals. CONCLUSIONS: This meta-analysis suggests that the CD14 -260C/T polymorphism may increase the risk of gastric cancer in H. pylori-infected individuals. However, large and well-designed studies are warranted to validate our findings.
Full Text Available In the present paper, we investigated the 5HTTLPR and STin2 polymorphisms in the promoter region of the serotonin transporter gene (SLC6A4, the G861C polymorphism (rs6296 of the serotonin receptor 1D beta (HTR1B, the T102C (rs6113 and C516T (rs6305 polymorphisms of the serotonin receptor gene subtype 2A (HTR2A, the DAT UTR, DAT intron 8 and DAT intron 14 of the dopamine transporter gene (SLC6A3, the Val-158-Met (rs4680 polymorphism of the COMT and the silent mutation G1287A (rs5569 in the norepinephrine transporter gene (SLC6A2. We genotyped 41 obsessive-compulsive disorder (OCD outpatients, classified as good-responders (n=27 and poor-responders (n=14 to treatment with clomipramine according to the Yale Brown Obsessive-Compulsive Scale (YBOCS. Patients who achieved a reduction in symptoms of 40% or more in YBOCS after 14 weeks of treatment were considered good-responders. Genotypes and alleles distribution of the investigated polymorphisms were compared between both groups. We did not find association between the studied polymorphisms and clomipramine response in our sample.
Feng, Y B; Fan, D Q; Yu, J; Bie, Y K
We conducted a case-control study to investigate the role of three common single nucleotide polymorphisms (SNPs) in the xeroderma pigmentosum complementation group G (XPG) gene (rs2094258, rs751402 and rs17655) in the development of gastric cancer in a Chinese population. Between January 2012 and December 2014, samples from a total of 177 patients with gastric cancer and 237 control subjects were collected from the Ankang City Central Hospital. XPG rs2094258, rs751402 and rs17655 polymorphisms were genotyped using polymerase chain reaction-restriction fragment length polymorphism. Using logistic regression analysis, we found that the CC genotype of rs17655 was associated with an elevated risk of gastric cancer, and the adjusted odds ratio (OR) and 95% confidence intervals (95%CI) were 1.91 and 1.07-3.41, respectively. Moreover, individuals carrying the GC + CC genotype of rs17655 had an increased susceptibility to gastric cancer (OR = 1.61, 95%CI = 1.03-2.54). However, we did not observe a significant association between XPG rs2094258 and rs751402 polymorphisms and development of gastric cancer. In conclusion, our study suggests that the rs17655 polymorphism in XPG is associated with an increased risk of gastric cancer. The results of our findings should be further validated by further large sample size studies. PMID:27323165
Zhou, B; Hu, X M; Wu, G Y
It has been suggested that the xeroderma pigmentosum complementation group G (XPG) gene Asp1104His polymorphism is linked to susceptibility to lung cancer. However, the results from the published studies are contradictory rather than conclusive. With this meta-analysis, we aimed to achieve a better understanding of the effects of the XPG gene Asp1104His polymorphism on lung cancer risk. We identified six eligible studies from five publications that included a total of 2293 lung cancer patients and 2586 controls. There was a significant association between the XPG gene Asp1104His polymorphism and lung cancer (His/His vs Asp/Asp: OR = 1.24, 95%CI = 1.04-1.48; Asp/His vs Asp/Asp: OR = 1.17, 95%CI = 1.03-1.34; the dominant model: OR = 1.18, 95%CI = 1.04-1.33; the recessive model: OR = 1.10, 95%CI = 0.94-1.28). In a subgroup analysis by nationality, we found a significant association between the XPG gene Asp1104His polymorphism and lung cancer risk in Asians. No publication bias was found in this study. The results from this meta-analysis indicate that the XPG gene Asp1104His polymorphism is associated with lung cancer risk, especially in Asians. PMID:27323149
SHU Qiang(舒 强); FANG Xiangming(方向明); CHEN Qixing(陈齐兴); Frank Stuber
Objective To investigate whether three biallelic polymorphisms at positions -592, -819 and -1082 in the promoter region of the IL-10 gene are associated with increased incidence of severe sepsis.Methods The IL-10 -592, -819 and -1082 polymorphisms were typed using polymerase chain reaction followed by digestion with the restriction enzymes RsaⅠ, MaeⅢ and MnlⅠ, respectively.Results Patients with severe sepsis were more likely to have IL-10 -1082 allele 1, compared with controls (P0.05). No significant differences in the genotype distribution and allele frequencies of the IL-10 -592 and IL-10 -819 polymorphisms were observed between patients with severe sepsis and heathy controls, nor between surviving and dead patients (P> 0.05). Conclusions The polymorphism at position -1082 in the promoter region of the IL-10 gene may be associated with susceptibility to severe sepsis. In constrast, the other two highly linked IL-10 polymorphisms are not associated with incidence or the outcome of severe sepsis.
Lu, Xiaolin; Wang, Zhen; Wang, Jianhua; Shangguan, Shaofang; Bao, Yihua; Lu, Ping; Wang, Li
Neural tube defects (NTDs) in mammals are rooted in aberrant neural tube closure during early embryogenesis, which is caused by multiple environmental and genetic factors. The Sonic Hedgehog pathway is involved in the induction of the floor plate and participates in formation of the neural tube. Mutation of the suppressor of fused gene (SUFU), an essential repressor of Sonic Hedgehog signaling pathway, can result in NTDs. A case-control study was designed to compare the frequencies of the polymorphism at four sites in the SUFU gene in control and NTDs group, as well as in subtype groups, including anencephaly, spina bifida and encephalocele. We also explored the association between polymorphism and NTDs risk in a high prevalence population in China. Rs10786691, but not the other three SNPs, had an association between polymorphisms and NTDs. The heterozygous AG allele of rs10786691 was significantly related with NTDs and encephalocele (OR = 1.60, 95% CI: 1.04-2.48, p = 0.034; OR = 2.83, 95% CI: 1.07-7.47, p = 0.036). In female but not male fetuses, the AG genotype of rs10786691 increased the risk of NTDs (OR = 1.88, 95% CI: 1.03-3.41, p = 0.040). The SUFU rs10786691 A>G polymorphism may be a potential risk factor for NTDs and encephalocele in this high-risk population, but the association between the polymorphism and NTDs was probably influenced by gender. PMID:24070372
Costa, Danielle de Souza; de Paula, Jonas J.; Alvim-Soares, Antonio M.; Pereira, Patrícia A.; Malloy-Diniz, Leandro F.; Rodrigues, Luiz O. C.; Romano-Silva, Marco A.; de Miranda, Débora M.
Neurofibromatosis type I (NF1) is a neurogenetic disease marked by multiple cognitive and learning problems. Genetic variants may account for phenotypic variance in NF1. Here, we investigated the association between the catechol-O-methyltransferase (COMT) Val158Met polymorphism and working memory and arithmetic performance in 50 NF1 individuals. A significant association of the COMT polymorphism was observed only with verbal working memory, as measured by the backward digit-span task with an advantageous performance for Met/Met carriers. To study how genetic modifiers influence NF1 cognitive performance might be of importance to decrease the unpredictability of the cognitive profile among NF1 patients. PMID:27458360
Full Text Available Jingwei Liu,1–2 Caiyun He,1–2 Quan Yuan,1–2 Zhenning Wang,1–2 Chengzhong Xing,1–2 Yuan Yuan1–2 1Tumor Etiology and Screening Department of Cancer Institute and General Surgery, The First Affiliated Hospital of China Medical University, 2Key Laboratory of Cancer Etiology and Prevention, China Medical University, Liaoning Provincial Education Department, Shenyang, People’s Republic of China Background: Results of the association between polymorphisms of osteopontin (OPN gene promoter region and risk of cancer were inconclusive. The aim of this meta-analysis was to elucidate whether OPN promoter polymorphisms were associated with cancer risk.Methods: Electronic databases including PubMed, Web of Science, and Chinese National Knowledge Infrastructure were systematically searched. Odd ratios (ORs and their 95% confidential interval (CI were used to assess the strength of association between OPN promoter polymorphisms and cancer risks.Results: Nine studies were finally included in this meta-analysis. For OPN rs17524488 polymorphism, carriers of GG or -/G genotype were significantly associated with increased cancer risk compared with wild-type -/- carriers, respectively (GG vs -/-: OR =1.40, 95% CI =1.03–1.91, P=0.033; -/G vs -/-: OR =1.22, 95% CI =1.07–1.40, P=0.002. Additionally, G allele was significantly associated with increased cancer risk compared with (- allele (OR =1.21, 95% CI =1.04–1.40, P=0.016. However, no significant association was observed of OPN rs11730582 polymorphism and cancer risk (CC vs TT: OR =0.98, 95% CI =0.49–1.97, P=0.964; CT vs TT: OR =0.88, 95% CI =0.54–1.43, P=0.610.Conclusion: Carriers of GG or -/G genotype of OPN promoter rs17524488 (-156-/G polymorphism might be associated with increased risk of cancer compared with wild-type -/- carriers, respectively. However, no significant association was observed between OPN promoter rs11730582 (-443C/T polymorphism and risk of cancer. Keywords: OPN
Full Text Available Metabolic syndrome (MetS is among the most important public health problems worldwide, and is recognized as a major risk factor for various illnesses, including type 2 diabetes mellitus, obesity, and cardiovascular diseases. Recently, oxidative stress has been suggested as part of MetS aetiology. The heme oxygenase 1 (HMOX1 and NADH:quinone oxidoreductase 1 (NQO1 genes are crucial mediators of cellular defence against oxidative stress. In the present study, we analysed the associations of HMOX1 (GTn and NQO1 C609T polymorphisms with MetS and its components. Our study population comprised 735 Mexican Mestizos unrelated volunteers recruited from different tertiary health institutions from Mexico City. In order to know the HMOX1 (GTn and NQO1 C609T allele frequencies in Amerindians, we included a population of 241 Amerindian native speakers. Their clinical and demographic data were recorded. The HMOX1 (GTn polymorphism was genotyped using PCR and fluorescence technology. NQO1 C609T polymorphism genotyping was performed using TaqMan probes. Short allele (<25 GT repeats of the HMOX1 polymorphism was associated with high systolic and diastolic blood pressure, and the T allele of the NQO1 C609T polymorphism was associated with increased triglyceride levels and decreased HDL-c levels, but only in individuals with MetS. This is the first study to analyse the association between MetS and genes involved in oxidative stress among Mexican Mestizos. Our data suggest that polymorphisms of HMOX1 and NQO1 genes are associated with a high risk of metabolic disorders, including high systolic and diastolic blood pressure, hypertriglyceridemia, and low HDL-c levels in Mexican Mestizo individuals.
Full Text Available Abstract Background Surfactant proteins (SP are important for the innate host defence and essential for a physiological lung function. Several linkage and association studies have investigated the genes coding for different surfactant proteins in the context of pulmonary diseases such as chronic obstructive pulmonary disease or respiratory distress syndrome of preterm infants. In this study we tested whether SP-B was in association with two further pulmonary diseases in children, i. e. severe infections caused by respiratory syncytial virus and bronchial asthma. Methods We chose to study five polymorphisms in SP-B: rs2077079 in the promoter region; rs1130866 leading to the amino acid exchange T131I; rs2040349 in intron 8; rs3024801 leading to L176F and rs3024809 resulting in R272H. Statistical analyses made use of the Armitage's trend test for single polymorphisms and FAMHAP and FASTEHPLUS for haplotype analyses. Results The polymorphisms rs3024801 and rs3024809 were not present in our study populations. The three other polymorphisms were common and in tight linkage disequilibrium with each other. They did not show association with bronchial asthma or severe RSV infection in the analyses of single polymorphisms. However, haplotypes analyses revealed association of SP-B with severe RSV infection (p = 0.034. Conclusion Thus our results indicate a possible involvement of SP-B in the genetic predisposition to severe RSV infections in the German population. In order to determine which of the three polymorphisms constituting the haplotypes is responsible for the association, further case control studies on large populations are necessary. Furthermore, functional analysis need to be conducted.
Tang, Y; Li, H; Li, J; Yu, F; Yu, J
Leptin is a hormone that affects the regulation of body weight, energy expenditure, fat metabolism, food intake, and appetite. In this study, we cloned the jlLEP-A1 and jlLEP-A2 genes in Jian carp (Cyprinus carpio var. Jian) and performed an association analysis between identified polymorphisms and growth traits. Three polymorphisms in exons of jlLEP-A1 (A1-T113C) and jlLEP-A2 (A2-G415A and A2-G427A) were identified, and genotyped by the polymerase chain reaction - restriction fragment length polymorphism method in 263 female and 294 male Jian carp. All three SNPs were missense mutations. Association analysis revealed that the three SNPs were significantly associated with growth traits in male Jian carp. Only SNP A1-T113C was significantly associated with growth traits in female Jian carp. Analysis of diplotypes derived from jlLEP-A2 SNPs revealed an association with growth traits in male but not female Jian carp. These results demonstrate that polymorphisms in the leptin gene are associated with growth traits and may be used for marker-assisted selection programs in Jian carp breeding and production. PMID:27525905
Koh, Min Jung; Kim, Wonji; Kang, Jee In; Namkoong, Kee; Kim, Se Joo
Oxytocin receptor gene single nucleotide polymorphisms have been associated with structural and functional alterations in brain regions, which involve social-emotional processing. Therefore, oxytocin receptor gene polymorphisms may contribute to individual differences in alexithymia, which is considered to be a dysfunction of emotional processing. The aim of this study was to evaluate the association between oxytocin receptor gene single nucleotide polymorphisms or haplotypes and alexithymia ...
Ross, Owen A; Curran, Martin D; Rea, I Maeve; Hyland, Paul; Duggan, Orla; Barnett, Christopher R; Annett, Kathryn; Patterson, Chris; Barnett, Yvonne A; Middleton, Derek
Polymorphism of the human leukocyte antigen has been implicated in a number of autoimmune disorders including ageing. In the course of the present study, no association of the human leukocyte antigen (HLA)-A1, B8, DR3 haplotype with a male Irish aged population, as previously reported, was observed. Two polymorphic nucleotides in the TNF cluster (G-308A TNF-alpha and G+252A TNF-beta), associated with increased TNF-alpha production, were shown to be in tight linkage disequilibrium with the class I and II HLA loci, generating HLA haplotypes with extended linkage disequilibrium. However, no age-related allele or genotype frequencies were observed for either polymorphic nucleotide. PMID:12714268
João Paulo Lopes Born
Full Text Available Juvenile myoclonic epilepsy (JME accounts for 26% of generalized idiopathic epileptic syndromes. The highest levels of thrombin activity are closely involved in the development of neurological diseases, including epilepsy. The prothrombin c.20210G>A (rs1799963 variation, which alters prothrombin mRNA stability, is associated with high plasma prothrombin levels. Objective : The present study was designed to investigate whether the SNP rs1799963 is a risk factor for JME in the northeastern Brazilian population. Results : The polymorphism was genotyped in 207 controls and 123 patients using polymerase chain reaction-restriction fragment length polymorphism method. No significant differences were observed in the genotype and allele frequencies of this polymorphism between cases and controls. Conclusion : These results present no evidence for an association of rs1799963 with JME. Further studies including other types of epilepsy are required to investigate the involvement of prothrombin gene in the genetic susceptibility to chronic seizure.
Full Text Available The promoter region of human Interleukin −10 gene is highly polymorphic and has been associated with numerous autoimmune diseases. Recent studies have linked vitiligo with defective autoimmune system. This study is aimed to explore a possible association between IL-10 gene polymorphism and vitiligo in Saudi population. This case control study consisted of 184 Saudi subjects including 83 vitiligo patients (40 males, 43 females mean age 27.85 ± 12.43 years and 101 matched controls. Genomic DNA was extracted from the blood samples of healthy controls and Vitiligo patients visiting out patient clinic of Department of Dermatology, Riyadh Armed Forces Hospital, using QIA ampR DNA mini kit (Qiagen CA, USA. Interleukin-10 gene was amplified by polymerase chain reaction (PCR using Arms primers to detect any polymorphism involved at positions −592, −819 and −1082.
Taufer, Maristela; Peres, Alessandra; de Andrade, Vanessa Moraes; de Oliveira, Graziela; Sá, Gustavo; do Canto, Margo Etiene Pazzato; dos Santos, Adriana Ritter; Bauer, Moisés E; da Cruz, Ivana Beatrice Mânica
Oxidative stress has been related to aging. Recent evidences suggest that a genetic dimorphism that encodes for either alanine or valine in superoxide dismutase (SOD2) is involved with oxidative stress. However, the current literature is still controversial, and the potential role of the Ala16Val polymorphism in human aging needs to be established. Here we investigated the role of the SOD2 polymorphism in: a) age-related mortality, b) morbidity (breast and prostate cancer), c) immunological markers, and d) DNA damage in peripheral blood cells. We did not find an association between SOD2 polymorphisms and mortality. However, the AA genotype was associated with increased risk for prostate and breast cancer, immunosenescence profile, as well as DNA damage. These data suggest that SOD2 presents characteristics that support the free radical theory of aging. PMID:15933380
Kasim, Nor Bahirah; Huri, Hasniza Zaman; Vethakkan, Shireene Ratna; Ibrahim, Luqman; Abdullah, Bashar Mudhaffar
Generally, obese and overweight individuals display higher free fatty acid levels, which stimulate insulin resistance. The combination of overweight or obesity with insulin resistance can trigger Type 2 diabetes mellitus (T2DM) and are primary contributing factors to the development of uncontrolled T2DM. Genetic polymorphisms also play an important role as they can impact a population's susceptibility to becoming overweight or obese and developing related chronic complications, such as uncontrolled T2DM. This review specifically examines the genetic polymorphisms associated with overweight and obesity in patients with uncontrolled T2DM. Particularly, gene polymorphisms in ADIPOQ (rs1501299 and rs17300539), LepR (rs1137101 and rs1045895), IRS2 (rs1805092), GRB14 (rs10195252 and rs3923113) and PPARG (rs1801282) have been associated with overweight and obesity in uncontrolled T2DM. PMID:26999420
Full Text Available Objective: To study the association between ADAM33 and keloid scars in the northeastern Chinese population. Methods: A total of 283 keloid scar patients and a control group of 290 healthy volunteers were recruited for this study. Six polymorphic loci (V4, T+1, T2, T1, S2 and Q-1 of ADAM33 were selected for genotyping. Genotypes were determined by using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP method. Results: We observed the frequency of the rs612709 A allele exhibited a significantly decreased frequency in cases than in controls(22 vs.39.6%, PP= 0.041. In contrast, the haplotype H8 (GGGAGG was more common in the control group than in the case group (P=0.022. Conclusions: Our data suggest that the ADAM33 polymorphisms may be associated with keloid scars in the northeastern Chinese population.
Amankwah, Ernest K; Kelemen, Linda E; Wang, Qinggang;
BACKGROUND: We previously reported an association between rs2660753, a prostate cancer susceptibility polymorphism, and invasive epithelial ovarian cancer (EOC; OR = 1.2, 95% CI=1.0-1.4, P(trend) = 0.01) that showed a stronger association with the serous histological subtype (OR = 1.3, 95% CI = 1.......0-1.2, P(trend) = 0.11). There was no evidence for statistical heterogeneity in ORs across the studies. CONCLUSIONS: Although rs2660753 is a strong prostate cancer susceptibility polymorphism, the association with another hormonally related cancer, invasive EOC, is not supported by this replication study.......1-1.5, P(trend) = 0.003). METHODS: We sought to replicate this association in 12 other studies comprising 4,482 cases and 6,894 controls of white non-Hispanic ancestry in the Ovarian Cancer Association Consortium. RESULTS: No evidence for an association with all cancers or serous cancers was observed in a...
Full Text Available Abstract Background Catechol-O-methyltransferase (COMT is one of the most important enzymes involved in estrogen metabolism and its functional genetic polymorphisms may be associated with breast cancer (BC risk. Many epidemiological studies have been conducted to explore the association between the COMT Val158Met polymorphism and breast cancer risk. However, the results remain inconclusive. In order to derive a more precise estimation of this relationship, a large meta-analysis was performed in this study. Methods Systematic searches of the PubMed, Embase and Cochrane Library were performed. Crude odds ratios (ORs with 95% confidence intervals (CIs were calculated to estimate the strength of the association. Results A total of 56 studies including 34,358 breast cancer cases and 45,429 controls were included. Overall, no significant associations between the COMT Val158Met polymorphism and breast cancer risk were found for LL versus HH, HL versus HH, LL versus HL, recessive model LL versus HL+HH, and dominant model LL+HL versus HH. In subgroup analysis by ethnicity, source of controls, and menopausal status, there was still no significant association detected in any of the genetic models. Conclusion Our meta-analysis results suggest that the COMT Val158Met polymorphism may not contribute to breast cancer susceptibility. Virtual slides The virtual slides(s for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs4806123577708417
Karolina Maria Burghardt
Full Text Available Recently, genetic associations have been described in intestinal transplants. Namely, Crohn's disease susceptibility gene NOD2 polymorphisms have been reported to be more prevalent in patients with graft failure following intestinal transplantation (IT. Therefore, we sought to determine if polymorphisms in the NOD2 signaling cascade, including NOD2, CARD9, RAC1 and ATG16L1 are associated with intestinal failure (IF or its complications. We carried out a cross-sectional study of 59 children with IF and 500 healthy Caucasian controls. Using the Taqman platform we determined the prevalence of NOD2 as well as ATG16L1, RAC1 and CARD9 SNPs. NOD2 pathway polymorphisms were evaluated in relation to outcomes of episodes of sepsis, ICU admissions, hyperbilirubinemia and need for IT. We found that the minor allele of a CARD9 SNP was associated with protection from developing IF when compared to healthy controls and was also associated with decreased odds of sustained conjugated hyperbilirubinemia. Therefore, IF patients with CARD9 polymorphism are less likely to develop progressive liver disease and suggests that host innate immunity may play a role in IF associated liver disease.
Burghardt, Karolina Maria; Avinashi, Vishal; Kosar, Christina; Xu, Wei; Wales, Paul W; Avitzur, Yaron; Muise, Aleixo
Recently, genetic associations have been described in intestinal transplants. Namely, Crohn's disease susceptibility gene NOD2 polymorphisms have been reported to be more prevalent in patients with graft failure following intestinal transplantation (IT). Therefore, we sought to determine if polymorphisms in the NOD2 signaling cascade, including NOD2, CARD9, RAC1 and ATG16L1 are associated with intestinal failure (IF) or its complications. We carried out a cross-sectional study of 59 children with IF and 500 healthy Caucasian controls. Using the Taqman platform we determined the prevalence of NOD2 as well as ATG16L1, RAC1 and CARD9 SNPs. NOD2 pathway polymorphisms were evaluated in relation to outcomes of episodes of sepsis, ICU admissions, hyperbilirubinemia and need for IT. We found that the minor allele of a CARD9 SNP was associated with protection from developing IF when compared to healthy controls and was also associated with decreased odds of sustained conjugated hyperbilirubinemia. Therefore, IF patients with CARD9 polymorphism are less likely to develop progressive liver disease and suggests that host innate immunity may play a role in IF associated liver disease. PMID:24465786
Coppedè, Fabio; Lo Gerfo, Annalisa; Carlesi, Cecilia; Piazza, Selina; Mancuso, Michelangelo; Pasquali, Livia; Murri, Luigi; Migliore, Lucia; Siciliano, Gabriele
Impairments in DNA repair enzymes have been observed in amyotrophic lateral sclerosis (ALS) tissues, particularly in the activity of the apurinic/apyrimidinic endonuclease 1 (APEX1). Moreover, it was suggested that the common APEX1 Asp148Glu polymorphism might be associated with ALS risk. To further address this question we performed the present study aimed at evaluating the contribution of the APEX1 Asp148Glu polymorphism in sporadic ALS (sALS) risk and clinical presentation, including age and site of onset and disease progression. We screened 134 sALS Italian patients and 129 matched controls for the presence of the APEX1 Asp148Glu polymorphism. No difference in APEX1 Asp148Glu allele and genotype frequencies was found between the groups, nor was the polymorphism associated with age and site of onset or disease progression. Present results do not support a role for the APEX1 Asp148Glu polymorphism in sALS pathogenesis in the Italian population. PMID:18482781
Full Text Available The mitochondrial (mt DNA C5178A and A10398G polymorphisms have been reported to be associated with mental disorders such as bipolar disorder. However, the effects of these polymorphisms on temperament in healthy people are poorly understood. Evaluating healthy subjects can have the advantage of providing new strategies for maintaining psychological health and preventing mental illness. We examined the association between mtDNA polymorphisms and temperament in Japanese students. There was no significant difference in examined temperament when analysed by genotypes, 5178-10398 haplotypes, or sex. The subgroup analysis based on sex indicated that there was an interactive effect of the mtDNA A10398G polymorphism and sex on anxiety and obsession. This finding is preliminary and cannot exclude the possibility of false-positive due to small sample size (144 subjects and multiple statistical testing. Further studies involving a larger sample size or other ethnic groups are necessary to confirm that mtDNA A10398G polymorphism can be a genetic factor for temperament.
Ping-I Hsu; Jin-Liang Chen; Yu-Shan Chen; Angela Chen; Jyh-Jen Jwo; Hui-Hwa Tseng; Kwok-Hung Lai; Gin-Ho Lo; Ching-Chu Lo; Chung-Jen Wu; Seng-Kee Chuah; Il- Ran Hwang
AIM: To eluddate the relations between the myeloperoxidase -468G→A polymorphism and the development of duodenal ulcer (DU), and to investigate the impacts of this host genetic polymorphism on the histopathological featuresof Helicobacter pylori ( H pylori)-related gastritis. METHODS: In a case-control study of 115 consecutive DU patients and 182 controls, the myeloperoxidase-468G→A polymorphism was genotyped. Additionally, gastric mucosal changes were examined according to the updated Sydney System.RESULTS: The two study groups differed in the distributionsof myelperoxidase genotypes (P= 0.008). All six individuals carrying myeloperoxidase A/A genotypes were in the DU group. The carriage of myeloperoxidase allele A and H pylori infection were associated with an increased risk of DU with odds ratios (OR) of 2.3 and 5.8, respectively. Thecombined risk of the carriage of myeloperoxidase allele A and H pylori infection for DU was 8.7 (95% CI, 3.5-21.8). In the H pylori-infected individuals, allele A carriers displayed higher bacterial density scores (P = 0.04) inthe antrum than did non-carriers.CONCLUSION: This work verifies for the first time the association of myeloperoxidase-468G→A polymorphism with antral H pyloridensity and DU disease. The mechanisms underlying this genetic polymorphism in developing DU disease merit further investigations.
Full Text Available Background and Aims: Chronic inflammatory process plays an important role in atherothrombosis. Interleukin-1 (IL-1 is one of the key modulators of the inflammatory response and its activity is critically regulated by its receptor antagonist (IL-1Ra. A variable number tandem repeat polymorphism in intron 2 of IL-1Ra gene and a C to T single base polymorphism in the promoter of IL-1β gene (C-511 ®T have been reported to affect the levels of IL-1 as well as its antagonist, IL-1Ra. It is also reported in several studies that these polymorphisms are associated with the susceptibility to cardio-cerebral vascular disease. However, data are limited in China. In this article, we studied the relationships between these polymorphisms and the risk of ischemic stroke in China. Materials and Methods: One hundred and twelve patients committed ischemic stroke were compared with 95 demographically matched healthy volunteers. Results: The frequencies of the IL-1Ra 1/1 genotype and IL-1Ra allele 1 (RaFNx011 allele in stroke patients were significantly higher than those in healthy volunteers [93.7% vs. 82.1%, P =0.014; 0.964 vs. 0.905, P =0.007]. No significant differences were found in the IL-1β -511 genotype and the allele distribution between the two groups. Conclusions: Our results implicated that IL-1 gene polymorphism might be associated with the susceptibility to ischemic stroke.
Full Text Available Abstract Backgroud Interleukin-10(IL-10 is a multifunctional cytokine with both immunosuppressive and antiangiogenic functions. Polymorphisms in the IL-10 gene promoter genetically determine interindividual differences in IL-10 production. This study was performed to determined whether polymorphisms in the IL-10 gene promoter were associated with breast cancer in a Chinese Han population. Methods We genotyped 315 patients with breast cancer and 322 healthy control subjects for -1082A/G, -819T/C and -592A/C single nucleotide polymorphisms in the promoter region of the IL-10 gene by polymerase chain reactionerestriction fragment length polymorphism (PCR-RFLP. Results There were no significant differences in genotype, allele, or haplotype frequencies in all three loci between patients and healthy controls. Analysis of breast cancer prognostic and predictive factors revealed that the -1082AA genotype was associated with a significantly increased risk of lymph node (LN involvement (P = 0.041 and larger tumor size (P = 0.039 at the time of diagnosis. Furthermore, in the haplotype analysis of IL-10 gene, we found that patients carrying ATA haplotype were in higher LN involvement (p = 0.022 and higher tumor stage(p = 0.028 of breast cancer at the time of diagnosis compared with others. Conclusions Our findings suggest that IL-10 promoter polymorphisms participate in the progression of breast cancer rather than in its initial development in Chinese Han women.
Giannakopoulos, Marios P; Antonacopoulou, Anna G; Kottorou, Anastasia E; Kalofonos, Haralabos P; Gartaganis, Sotirios P
Purpose In this study we aimed to evaluate the polymorphism at codon 129 (M129V) of the PRNP gene as a secondary risk factor for pseudoexfoliation syndrome (PEX). Methods Two hundred and seventy-five unrelated subjects, including 156 patients with PEX and 119 unrelated control subjects, were recruited from the University Hospital of Patras, Greece. All patients and controls were of Caucasian or European ancestry. The PRNP M129V (A/G) single-nucleotide polymorphism was genotyped by real-time polymerase chain reactions. Association of the polymorphism with PEX was assessed using the two-sided Pearson’s chi-squared or Fisher’s exact test. Result No significant difference between patients and controls was observed in terms of frequencies of alleles and genotypes of the PRNP gene. Conclusion Polymorphism at M129V of the PRNP gene was evaluated as a secondary risk factor for developing PEX. Our results suggest that this PRNP gene polymorphism is not associated with PEX.
Full Text Available Jun Chen,1,* Xue-Ming Ying,2,* Xue-Ming Huang,3 Peng Huang,4 Shao-Cong Yan1 1Department of Oncology, The First Affiliated Hospital of Nanchang University, Nanchang, 2Department of Oncology, Jingdezhen City People’s Hospital, Jingdezhen, 3Department of Urology, Research Institute, The First Affiliated Hospital of Nanchang University, 4The Medical School of Nanchang University, School of Public Health, Nanchang, People’s Republic of China*These authors contributed equally to this workAbstract: Inflammation represents an important event which facilitates prostate carcinogenesis. Genetic variations in inflammatory response genes could affect the level and function of the protein products, resulting in the differential prostate cancer risk among carriers of different variants. This study attempted to investigate the association of IL-4 rs2243250, IL-6 rs10499563, IL-8 rs4073, as well as NFKBIA rs2233406 and rs3138053 polymorphisms with prostate cancer risk in the Chinese population. Genotyping of the polymorphisms was performed by using polymerase chain reaction-restriction fragment length polymorphism technique on 439 prostate cancer patients and 524 controls, and the association of each polymorphic genotype with prostate cancer risk was evaluated by using logistic regression analysis based on allele, heterozygous, and homozygous comparison models, with adjustment to age and smoking status. We showed that the C allele of IL-4 rs2243250 polymorphism could increase prostate cancer risk (heterozygous comparison model: odds ratio [OR] =1.434, 95% confidence interval [CI] =1.092–1.881, P=0.009; homozygous comparison model: OR =2.301, 95% CI =1.402–3.775, P=0.001; allele comparison model: OR =1.509, 95% CI =1.228–1.853, P<0.001. On the other hand, the C allele of rs10499563 polymorphism could decrease prostate cancer risk (heterozygous comparison model: OR =0.694, 95% CI =0.525–0.918, P=0.010; homozygous comparison model: OR =0.499, 95% CI =0
Shiao, S. P. K.; Yu, C H
The methylenetetrahydrofolate reductase (MTHFR) gene is one of the most investigated of the genes associated with chronic human diseases because of its associations with hyperhomocysteinemia and toxicity. It has been proposed as a prototype gene for the prevention of colorectal cancer (CRC). The major objectives of this meta-analysis were to examine the polymorphism-mutation patterns of MTHFR and their associations with risk for CRC as well as potential contributing factors for mutations and ...
Itoh, Kanako; Hashimoto, Kenji; Shimizu, Eiji; Sekine, Yoshimoto; Ozaki, Norio; Inada, Toshiya; Harano, Mutsuo; Iwata, Nakao; Komiyama, Tokutaro; Yamada, Mitsuhiko; Sora,Ichiro; Nakata, Kenji; Ujike, Hiroshi; Iyo, Masaomi
Several lines of evidence suggest that genetic factors might contribute to drug abuse vulnerability. Recent genomic scans for association demonstrated that the brain-derived neurotrophic factor (BDNF) gene was associated with drug abuse vulnerability. In this study, we analyzed association of two BDNF gene single nucleotide polymorphisms (SNPs), 132C>T (C270T named formerly) in the noncoding region of exon V and 196G >A (val66met) in the coding region of exon XIIIA, with methamphetamine (MAP)...
Dogru, Hatice Yilmaz; Ozsoy, Asker Zeki; Karakus, Nevin; Delibas, Ilhan Bahri; Isguder, Cigdem Kunt; Yigit, Serbulent
Primary dysmenorrhea, which affects 90 % of adolescent girls and more than 50 % of menstruating women worldwide, is characterized by recurrent pain during menses in the absence of a detectable organic disease. The aim of this study is to assess the association between MIF -173 and TNF -308 genetic polymorphisms and the clinical features of primary dysmenorrhea. The study population comprised 154 unrelated female patients with clinical diagnosis of dysmenorrhea, and a total of 144 control subjects were recruited consecutively. The MIF -173G > C promoter polymorphism (rs755622) and TNF gene -308G > A (rs1800629) polymorphism were analyzed by polymerase chain reaction-based restriction fragment length polymorphism assay. Two fragments (268 and 97 bp) were seen when the G allele was present at position -173, and three fragments (206, 97, and 62 bp) were observed when the C allele was present. Two fragments (87 and 20 bp) were seen when G allele was present at position -308. There were statistically significant associations between age at menarche and history of back pain among dysmenorrhea patients and MIF gene -173G > C polymorphism (p = 0.003 and p = 0.042, respectively). The genotype and allele frequencies of -308G > A polymorphism showed statistically significant differences between dysmenorrhea patients and controls (p = 0.023 and p = 0.009, respectively). A high association was also observed when the patients were compared with the controls according to the GG genotype versus GA+AA genotypes (p = 0.009). The present study showed that the TNF-α -308 GG genotype may be a useful tool to predict the susceptibility of dysmenorrhea. PMID:27105877
Liefers, S.C.; Pas, te M.F.W.; Veerkamp, R.F.; Chilliard, C.; Delavaud, C.; Gerritsen, R.; Lende, van der T.
Leptin is a hormone produced by adipocytes, and its expression is regulated by body fatness and energy balance. This study describes the association of four leptin gene polymorphisms in dairy cows (R4C, A59V, RFLP1, and BM1500) with circulating leptin concentrations during the periparturient period.
Yeh, Ting-Kuang; Chang, Chun-Yen; Hu, Chung-Yi; Yeh, Ting-Chi; Lin, Ming-Yeh
Catechol-O-methyltransferase (COMT) is a methylation enzyme that catalyzes the degradation pathway and inactivation of dopamine. It is accepted widely as being involved in the modulation of dopaminergic physiology and prefrontal cortex (PFC) function. The COMT Val158Met polymorphism is associated with variation in COMT activity. COMT 158Met allele…
The objective of this study was to assess polymorphisms within lipogenic-related candidate genes for association with the reproductive traits; age at puberty (AP), ovulation rate (OR), and weaning-to-estrus interval (WEI). Variations within the anorectic gene Cocaine- and Amphetamine-Regulated Trans...
The interaction between the Pro12Ala polymorphism in peroxisome-proliferator-activator receptor gamma PPARg -2 and physical activity in the association with obesity (BMI ≥30 kg m-2) was explored in 901 women and 903 men between 30 and 75 years participating in a population survey of cardiovascula...
Objective: To examine whether polymorphism within the tumor necrosis factor α（TNFα） gene is associated with the susceptibility and clinic manifestations to systemic lupus erythe matosus （SLE） in the patients of Han ethnic group collected from the Northern China. Methods: TNF1 and TNF2 subtypes
Full Text Available "nBackground: Molecular components of the dopamine receptor (DRD3 play an important role in the pathophysiology of schizophrenia (SCZ. Previous studies have demonstrated an association between the DRD3 Ser9Gly polymorphism and SCZ but the results have been inconclusive. "nMethod: In this study, we investigated this controversial association between the Ser9Gly (A/G polymorphism and SCZ using Malay cases-control (261 cases/157 controls samples. PCR-RFLP was performed to genotype the distribution of the DRD3 Ser9Gly polymorphism."nResults: Both healthy control and SCHZ patient groups were in of Hardy-Weinberg equilibrium for the analyzed genetic variability. There was a significant association between the genotype distribution DRD3 polymorphisms and SCZ (χ2= 9.359; df= 2; P= 0.009."nConclusion: We believe that further studies are required to examine the association between others dopamine-related genes and the behavioral phenotypes of SCZ.
Gregoor, Jochem G.; van der Weide, Jan; Loovers, Harriet M.; van Megen, Harold J.; Egberts, Toine C.; Heerdink, Eibert R.
Background Treatment with atypical antipsychotic agents is often complicated by dyslipidemia, which is a risk factor for cardiovascular disease. Objectives To determine whether the LEPR Q223R, the LEP -2548G/A, and the HTR2C -759C/T polymorphisms are associated with dyslipidemia in patients using at
Beaver, Kevin M.; Vaughn, Michael G.; Wright, John Paul; DeLisi, Matt; Howard, Matthew O.
Although academic achievement is a heritable construct, to date research has yet to explore its molecular genetic underpinnings. Drawing on data from the National Longitudinal Study of Adolescent Health, the current longitudinal study investigated the associations between polymorphisms in three dopaminergic genes (DAT1, DRD2, and DRD4) and…
Nyegaard, Mette; Demontis, Ditte; Thestrup, Britta Boserup; Hedemand, Anne; Sørensen, Karina Meden; Hansen, Thomas; Werge, Thomas; Hougaard, David Michael; Yolken, Robert H; Mortensen, Preben Bo; Mors, Ole; Børglum, Anders D
The human endogenous retrovirus HERV-K18 is located within intron 1 of CD48 on chromosome 1q and is still active in the human genome. Genetic variation in HERV-K18 single-nucleotide polymorphisms (SNPs) has previously been associated with an increased risk of schizophrenia (SZ) and with type 2...
Ramos Cirilo, Priscila Daniele; Rosa, Fabíola Encinas; Moreira Ferraz, Maria Fernanda;
Polycystic ovary syndrome (PCOS) is an endocrinopathy associated with infertility, diabetes and cardiovascular events. This study aimed to correlate polymorphisms of genes involved in the biosynthesis and metabolism of steroids and insulin action (CYP17A1, CYP19A1, AR, ESR1, ESR2, INSR, IGF2...
Palles, Claire; Chegwidden, Laura; Li, Xinzhong; Findlay, John M.; Farnham, Garry; Giner, Francesc Castro; Peppelenbosch, Maikel P.; Kovac, Michal; Adams, Claire L.; Prenen, Hans; Briggs, Sarah; Harrison, Rebecca; Sanders, Scott; MacDonald, David; Haigh, Chris; Tucker, Art; Love, Sharon; Nanji, Manoj; Decaestecker, John; Ferry, David; Rathbone, Barrie; Hapeshi, Julie; Barr, Hugh; Moayyedi, Paul; Watson, Peter; Zietek, Barbara; Maroo, Neera; Gay, Laura; Underwood, Tim; Boulter, Lisa; McMurtry, Hugh; Monk, David; Patel, Praful; Ragunath, Krish; Al Dulaimi, David; Murray, Iain; Koss, Konrad; Veitch, Andrew; Trudgill, Nigel; Nwokolo, Chuka; Rembacken, Bjorn; Atherfold, Paul; Green, Elaine; Ang, Yeng; Kuipers, Ernst J.; Chow, Wu; Paterson, Stuart; Kadri, Sudarshan; Beales, Ian; Grimley, Charles; Mullins, Paul; Beckett, Conrad; Farrant, Mark; Dixon, Andrew; Kelly, Sean; Johnson, Matthew; Wajed, Shahjehan; Dhar, Anjan; Sawyer, Elinor; Roylance, Rebecca; Onstad, Lynn; Gammon, Marilie D.; Corley, Douglas A.; Shaheen, Nicholas J.; Bird, Nigel C.; Hardie, Laura J.; Reid, Brian J.; Ye, Weimin; Liu, Geoffrey; Romero, Yvonne; Bernstein, Leslie; Wu, Anna H.; Casson, Alan G.; Fitzgerald, Rebecca; Whiteman, David C.; Risch, Harvey A.; Levine, David M.; Vaughan, Tom L.; Verhaar, Auke P.; van den Brande, Jan; Toxopeus, Eelke L.; Spaander, Manon C.; Wijnhoven, Bas P. L.; van der Laan, Luc J. W.; Krishnadath, Kausilia; Wijmenga, Cisca; Trynka, Gosia; McManus, Ross; Reynolds, John V.; O'Sullivan, Jacintha; MacMathuna, Padraic; McGarrigle, Sarah A.; Kelleher, Dermot; Vermeire, Severine; Cleynen, Isabelle; Bisschops, Raf; Tomlinson, Ian; Jankowski, Janusz
BACKGROUND & AIMS: Barrett's esophagus (BE) increases the risk of esophageal adenocarcinoma (EAC). We found the risk to be BE has been associated with single nucleotide polymorphisms (SNPs) on chromosome 6p21 (within the HLA region) and on 16q23, where the closest protein-coding gene is FOXF1. Subse
C. Palles (Claire); L. Chegwidden (Laura); X. Li (Xinzhong); J.M. Findlay (John M.); G. Farnham (Garry); F. Castro Giner (Francesc); M.P. Peppelenbosch (Maikel); M. Kovac (Michal); C.L. Adams (Claire L.); H. Prenen (Hans); S. Briggs (Sarah); R. Harrison (Rebecca); S. Sanders (Scott); D. Macdonald (David); K. Haigh (Katharina); A.T. Tucker (Art); S. Love (Sharon); M. Nanji (Manoj); J. Decaestecker (John); D.R. Ferry (David); B. Rathbone (Barrie); J. Hapeshi (Julie); H. Barr (Hugh); P. Moayyedi (Paul); P. Watson (Peter); B. Zietek (Barbara); N. Maroo (Neera); L. Gay (Laura); T. Underwood (Tim); L. Boulter (Lisa); H. McMurtry (Hugh); A.B. Monk (Alastair); P. Patel (Poulam); K. Ragunath (Krish); D. Al Dulaimi (David); I. Murray (Iain); C. Koss (Clara); A. Veitch (Andrew); N. Trudgill (Nigel); C. Nwokolo (Chuka); B. Rembacken; P. Atherfold (Paul); E.K. Green (Elaine K); Y. Ang (Yeng); E.J. Kuipers (Ernst); W. Chow (Wu); S. Paterson (Stuart); S. Kadri (Sudarshan); I. Beales (Ian); C. Grimley (Charles); P. Mullins (Paul); C. Beckett (Conrad); M. Farrant (Mark); A. Dixon (Andrew); S. Kelly (Sean); M. Johnson (Matthew); S. Wajed (Shahjehan); A. Dhar (Archana); E.J. Sawyer (Elinor); R. Roylance (Rebecca); L. Onstad (Lynn); M.D. Gammon (Marilie); D.A. Corley (Douglas); N. Shaheen (Nazima); N.C. Bird (Nigel); B.G.S. Hardie (Bruce); B.J. Reid (Brian); W. Ye (Weimin); G. Liu (Geoffrey); Y. Romero (Yvonne); L. Bernstein (Leslie); A.H. Wu (Anna H.); A.G. Casson (Alan); R.C. Fitzgerald (Rebecca); D.C. Whiteman (David C.); H. Risch (Harvey); D.M. Levine (David M.); T.L. Vaughan (Thomas); A.P. Verhaar (Auke); J. Van Den Brande (Jan); E.L.A. Toxopeus (Eelke); V.M.C.W. Spaander (Manon); B.P.L. Wijnhoven (Bas); L.J.W. van der Laan (Luc); K.K. Krishnadath (Kausilia); C. Wijmenga (Cisca); G. Trynka (Gosia); R. McManus (Ross); J.V. Reynolds (John V.); J. O'Sullivan (Jacintha); P. Macmathuna (Padraic); S.A. McGarrigle (Sarah A.); D. Kelleher (Dermot); S. Vermeire (Séverine); I. Cleynen (Isabelle); R. Bisschops (Raf); I.P. Tomlinson (Ian); J.A. Jankowski (Janusz Antoni)
textabstractBackground & Aims Barrett's esophagus (BE) increases the risk of esophageal adenocarcinoma (EAC). We found the risk to be BE has been associated with single nucleotide polymorphisms (SNPs) on chromosome 6p21 (within the HLA region) and on 16q23, where the closest protein-coding gene is F
Full Text Available PARP-1 is a nuclear enzyme that plays an important role in DNA repair, recombination, proliferation and the genome stability. The PARP-1 Val762Ala polymorphism has been associated with increased risk of developing cancers of the prostate, esophagus and lung. The aim of this study was to determine whether the PARP-1 Val762Ala polymorphism is associated with the risk of cervical carcinoma. MA-PCR was used to genotype the PARP-1 Val762Ala polymorphism in 539 women with cervical carcinoma, 480 women with CIN and 800 controls. The genotyping method was confirmed by the DNA sequencing analysis. The PARP-1 Val762Ala polymorphism was not associated with the risk of CIN. However, women carrying the PARP-1 Ala762Ala genotype were significantly susceptible to cervical carcinoma (OR: 2.70, 95% CI: 1.47-3.70, and the similar results were also found in squamous cell carcinoma (OR: 2.56, 95% CI: 1.47-3.70. In HPV positive population, the PARP-1 Ala762Ala genotype was also associated with increased risk of cervical carcinoma (OR: 5.56, 95% CI: 2.08-14.3. Our results indicate that the PARP-1 Ala762Ala genotype increases the risk of cervical carcinoma.
The objective was to assess the association of single nucleotide polymorphisms (SNP) developed on candidate genes residing under previously identified quantitative trait loci for marbling score and meat tenderness. Two hundred five SNP were identified on twenty candidate genes. Genes selected under ...
Kjær, Karina Hansen; Pahus, Jytte; Hansen, Mariann Fagernæs;
cellular RNAs which in turn inhibits protein translation and induces apoptosis. Several single nucleotide polymorphisms (SNPs) in the OAS1 gene have been associated with disease. We have investigated the functional effect of two common SNPs in the OAS1 gene. The SNP rs10774671 affects splicing to one of...
Beitelshees Amber L
Full Text Available Abstract Objective Leukocyte count has been associated with blood pressure, hypertension, and hypertensive complications. We hypothesized that polymorphisms in the CXCL5 gene, which encodes the neutrophilic chemokine ENA-78, are associated with blood pressure in cardiovascular disease (CVD-free adults and that these polymorphisms are functional. Methods and results A total of 192 community-dwelling participants without CVD or risk equivalents were enrolled. Two CXCL5 polymorphisms (−156 G > C (rs352046 and 398 G > A (rs425535 were tested for associations with blood pressure. Allele-specific mRNA expression in leukocytes was also measured to determine whether heterozygosity was associated with allelic expression imbalance. In −156 C variant carriers, systolic blood pressure (SBP was 7 mmHg higher than in −156 G/G wild-type homozygotes (131 ± 17 vs. 124 ± 14 mmHg; P = 0.008. Similarly, diastolic blood pressure (DBP was 4 mmHg higher in −156 C variant carriers (78 ± 11 vs. 74 ± 11 mmHg; P = 0.013. In multivariate analysis of SBP, age, sex, body mass index, and the −156 G > C polymorphism were identified as significant variables. Age, sex, and the −156 G > C SNP were further associated with DBP, along with white blood cells. Allelic expression imbalance and significantly higher circulating ENA-78 concentrations were noted for variant carriers. Conclusion CXCL5 gene polymorphisms are functional and associated with variable blood pressure in CVD-free individuals. The role of CXCL5 as a hypertension- and CVD-susceptibility gene should be further explored.
Jones, I M; Thomas, C B; Xi, T; Mohrenweiser, H W; Nelson, D O
Elucidating the relationship between polymorphic sequences and risk of common disease is a challenge. For example, although it is clear that variation in DNA repair genes is associated with familial cancer, aging and neurological disease, progress toward identifying polymorphisms associated with elevated risk of sporadic disease has been slow. This is partly due to the complexity of the genetic variation, the existence of large numbers of mostly low frequency variants and the contribution of many genes to variation in susceptibility. There has been limited development of methods to find associations between genotypes having many polymorphisms and pathway function or health outcome. We have explored several statistical methods for identifying polymorphisms associated with variation in DNA repair phenotypes. The model system used was 80 cell lines that had been resequenced to identify variation; 191 single nucleotide substitution polymorphisms (SNPs) are included, of which 172 are in 31 base excision repair pathway genes, 19 in 5 anti-oxidation genes, and DNA repair phenotypes based on single strand breaks measured by the alkaline Comet assay. Univariate analyses were of limited value in identifying SNPs associated with phenotype variation. Of the multivariable model selection methods tested: the easiest that provided reduced error of prediction of phenotype was simple counting of the variant alleles predicted to encode proteins with reduced activity, which led to a genotype including 52 SNPs; the best and most parsimonious model was achieved using a two-step analysis without regard to potential functional relevance: first SNPs were ranked by importance determined by Random Forests Regression (RFR), followed by cross-validation in a second round of RFR modeling that included ever more SNPs in declining order of importance. With this approach 6 SNPs were found to minimize prediction error. The results should encourage research into utilization of multivariate
Han, J-W; Wang, Y; Li, H-B; Alateng, C; Bai, Y-H; Sun, Z-Q; Lv, X-X; Wu, R-N
The polymorphisms of tumour necrosis factor alpha-induced protein 3 (TNFAIP3) have been found to associate with several autoimmune diseases. This study aimed to explore the association of single nucleotide polymorphisms (SNPs) of TNFAIP3 gene with systemic lupus erythematosus (SLE) in Han Chinese. Thirty-two SNPs were genotyped in 284 patients with SLE and 630 controls using the ligation detection reaction (LDR) method. The quality control steps and statistical analyses were performed using the plink 1.07 package and haploview software. We found that 13 SNPs in TNFAIP3 showed significant association with SLE (P 0.27). All 13 SNPs showed most significant association in the dominant model. In haplotype analysis, a long risk SNP haplotype (GCCCGTGTCATGG) showed most significant association (P = 1.00 × 10(-4) ). In conclusion, our data suggest that TNFAIP3 is a susceptible gene for SLE in the Han Chinese population. PMID:26846592
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
Liao, Ning; Chen, Min-Li; Zhao, Hua; Xie, Zheng-Fu
Background: There is no consensus regarding the association between polymorphisms in the myosin IXB (MYO9B) gene and celiac disease (CD) risk. In this study, we performed a meta-analysis to evaluate genetic variants in MYO9B with CD. Methods: Four MYO9B polymorphisms (rs1545620, rs1457092, rs2305767 and rs2305764) were assessed. A literature search was conducted using PubMed, Scopus, and Web of Science databases until June 2015. Odds ratio (OR) and 95% confidence interval (CI) were used to in...
Liu, Haitao; Jia, Jinlin; Mao, Xuemei; Lin, Zhiyong
Abstract Our meta-analysis was aimed to evaluate the association of CYP1A1 and glutathione-S-transferase M1 (GSTM1) polymorphisms with oral cancer susceptibility. The related articles were searched in PubMed, Embase, and CNKI databases. Fifty eligible studies were included in our meta-analysis. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to evaluate the relationship of CYP1A1 (rs4646903 and rs1048943) and GSTM1 polymorphisms with oral cancer risk. A random-effects model or...
Full Text Available Seasonal reproduction in sheep greatly limits the possibilities of continuous year-round production and equitable supply of sheep products on the market. The begging of breeding season in sheep is associated with melatonin secretion under the darkness influence. Melatonin, through specific G protein coupled receptors, MT1 and MT2, affects target tissues and organs. MTNR1A gene is located on 26th chromosome and has two polymorphic sites in sheep. The presence of polymorphism (M/M, R/R is related to non-seasonal presence of estrus, while absence of polymorphism (m/m, r/r is related to seasonal estrus presence. Individuals with "M" or "R" allele in homozygous or heterozygous form are characterized by more successful reproduction during long photoperiod or outside the usual breeding season.
Ahmed, Radwan H.; Huri, Hasniza Zaman; Al-Hamodi, Zaid; Salem, Sameer D.; Al-absi, Boshra; Muniandy, Sekaran
Background Genetic polymorphisms of the Dipeptidyl Peptidase 4 (DPP4) gene may play a role in the etiology of type 2 diabetes mellitus (T2DM). This study aimed to investigate the possible association of single nucleotide polymorphisms (SNPs) of the DPP4 gene in Malaysian subjects with T2DM and evaluated whether they had an effect on the serum levels of soluble dipeptidyl peptidase 4 (sDPP-IV). Method Ten DPP4 SNPs were genotyped by TaqMan genotyping assays in 314 subjects with T2DM and 235 controls. Of these, 71 metabolic syndrome (MetS) subjects were excluded from subsequent analysis. The odds ratios (ORs) and their 95% confidence interval (CIs) were calculated using multiple logistic regression for the association between the SNPs of DPP4 and T2DM. In addition, the serum levels of sDPP-IV were investigated to evaluate the association of the SNPs of DPP4 with the sDPP-IV levels. Results Dominant, recessive, and additive genetic models were employed to test the association of DPP4 polymorphisms with T2DM, after adjusting for age, race, gender and BMI. The rs12617656 was associated with T2DM in Malaysian subjects in the recessive genetic model (OR = 1.98, p = 0.006), dominant model (OR = 1.95, p = 0.008), and additive model (OR = 1.63, p = 0.001). This association was more pronounced among Malaysian Indians, recessive (OR = 3.21, p = 0.019), dominant OR = 3.72, p = 0.003) and additive model (OR = 2.29, p = 0.0009). The additive genetic model showed that DPP4 rs4664443 and rs7633162 polymorphisms were associated with T2DM (OR = 1.53, p = 0.039), and (OR = 1.42, p = 0.020), respectively. In addition, the rs4664443 G>A polymorphism was associated with increased sDPP-IV levels (p = 0.042) in T2DM subjects. Conclusions DPP4 polymorphisms were associated with T2DM in Malaysian subjects, and linked to variations in sDPP-IV levels. In addition, these associations were more pronounced among Malaysian Indian subjects. PMID:27111895
Alkhayal, Khayal A.; Awadalia, Zainab H.; Vaali-Mohammed, Mansoor-Ali; Al Obeed, Omar A.; Al Wesaimer, Alanoud; Halwani, Rabih; Zubaidi, Ahmed M.
Background Vitamin D, causally implicated in bone diseases and human malignancies, exerts its effects through binding to the vitamin D receptor (VDR). VDR is a transcription factor modulating the expression of several genes in different pathways. Genetic variants in the VDR gene have been associated with several cancers in different population including colorectal cancer. Objective To assess the association of VDR gene polymorphisms in relation with colorectal cancer (CRC) in a Saudi population. Methods The polymorphisms of VDR gene (BsmI, FokI, ApaI and TaqI) were analyzed by the polymerase chain reaction amplification of segments of interest followed by Sanger sequencing. One hundred diagnosed CRC patients and 100 healthy control subjects that were age and gender matched were recruited. Results We did not observe significant association of any of the four VDR polymorphisms with colorectal cancer risk in the overall analysis. Although not statistically significant, the AA genotype of BsmI conferred about two-fold protection against CRCs compared to the GG genotype. Stratification of the study subjects based on age and gender suggests statistically significant association of CRC with the ‘C’ allele of ApaI in patients >57 years of age at disease diagnosis and BsmI polymorphism in females. In addition, statistically significant differences were observed for the genotypic distributions of VDR-BsmI, ApaI and TaqI SNPs between Saudi Arabian population and several of the International HapMap project populations. Conclusion Despite the absence of correlation of the examined VDR polymorphisms with CRCs in the combined analysis, ApaI and BsmI loci are statistically significantly associated with CRC in elderly and female patients, respectively. These findings need further validation in larger cohorts prior to utilizing these SNPs as potential screening markers for colorectal cancers in Saudi population. PMID:27309378
Kumar, Jitender; Das, Swapan K; Sharma, Priyanka; Karthikeyan, Ganesan; Ramakrishnan, Lakshmy; Sengupta, Shantanu
An elevated level of homocysteine is an independent risk factor for cardiovascular diseases and is associated with other complex disorders. Homocysteine levels can be elevated due to dietary and/or genetic factors. A majority of Indian population have a low level of vitamin B12 (presumably due to vegetarian diet)--a critical nutritional factor, deficiency of which results in hyperhomocysteinemia. Hence, polymorphisms in the genes responsible for homocysteine metabolism can be perceived to have a greater impact in relation to hyperhomocysteinemia in Indian population. For this reason, the effects of diet and/or methylenetetrahydrofolate reductase (MTHFR) polymorphism were assessed in 200 individuals having varying homocysteine levels. Homocysteine levels were significantly elevated in individuals adhering to a vegetarian diet (P = 0.019) or having MTHFR A1298C polymorphism (P = 0.006). The minor allele frequency (MAF) of MTHFR C677T and A1298C was 0.15 and 0.44 respectively in this cohort. Since the MAF of these polymorphisms differed considerably from Caucasian and other Asian populations, frequencies of these polymorphisms were also determined in more than 400 individuals from different ethnic populations, selected from the entire country based on their geographical location and linguistic lineage, and was found to be similar to that of our cohort. The fact that MTHFR A1298C polymorphism is significantly associated with homocysteine levels, and that the CC genotype is present at a higher frequency in the Indian population, makes it extremely relevant in terms of its potential impact on hyperhomocysteinemia. PMID:16244782
Shukla, Sanket Kumar; Prasad, Kashi Nath; Tripathi, Aparna; Jaiswal, Virendra; Khatoon, Jahanarah; Ghsohal, Uday Chand; Krishnani, Narendra; Husain, Nuzhat
CagL is a pilus protein of Helicobacter pylori that interacts with host cellular α5β1 integrins through its arginine-glycine-aspartate (RGD) motif, guiding proper positioning of the T4SS and translocation of CagA. Deletion or sequence variations of cagL significantly diminished the ability of H. pylori to induce secretion of IL-8 by the host cell. Therefore, this study was undertaken to investigate the association of cagL and its amino acid sequence polymorphisms with gastric cancer (GC), peptic ulcer disease (PUD), and non-ulcer dyspepsia (NUD) as there are no such studies from India. In total, 200 adult patients (NUD 120, PUD 30, GC 50) who underwent an upper gastrointestinal endoscopy were enrolled. H. pylori infection was diagnosed by rapid urease test, culture, histopathology, and PCR. The collected isolates were screened for cagL genotype by PCR and assessed for amino acid sequence polymorphisms using sequence translation. The prevalence of H. pylori infection in study population was 52.5%. Most of the isolates were cagL genopositive (86.6%), and all had RGD motif in their amino acid sequences. D58 and K59 polymorphisms in cagL-genopositive strains were significantly higher in GC patients (P < 0.05). Combined D58K59 polymorphism was associated with higher risk of GC (3.8-fold) when compared to NUD. In conclusion, H. pylori cagL amino acid polymorphisms such as D58K59 are correlated with a higher risk of GC in the Indian population. Further studies are required to know the exact role of particular cagL amino acid polymorphisms in the pathogenicity of H. pylori infection. PMID:22941498
Full Text Available Several studies have shown that mutations and polymorphisms in clock genes are associated with abnormal circadian parameters in humans and also with more subtle non-pathological phenotypes like chronotypes. However, there have been conflicting results, and none of these studies analyzed the combined effects of more than one clock gene. Up to date, association studies in humans have focused on the analysis of only one clock gene per study. Since these genes encode proteins that physically interact with each other, combinations of polymorphisms in different clock genes could have a synergistic or an inhibitory effect upon circadian phenotypes. In the present study, we analyzed the combined effects of four polymorphisms in four clock genes (Per2, Per3, Clock and Bmal1 in people with extreme diurnal preferences (morning or evening. We found that a specific combination of polymorphisms in these genes is more frequent in people who have a morning preference for activity and there is a different combination in individuals with an evening preference for activity. Taken together, these results show that it is possible to detect clock gene interactions associated with human circadian phenotypes and bring an innovative idea of building a clock gene variation map that may be applied to human circadian biology.
Taschereau-Dumouchel, Vincent; Hétu, Sébastien; Bagramian, Anaït; Labrecque, Alexandre; Racine, Marion; Chagnon, Yvon C; Jackson, Philip L
Empathy is an important driver of human social behaviors and presents genetic roots that have been studied in neuroimaging using the intermediate phenotype approach. Notably, the Val66Met polymorphism of the Brain-derived neurotrophic factor (BDNF) gene has been identified as a potential target in neuroimaging studies based on its influence on emotion perception and social cognition, but its impact on self-reported empathy has never been documented. Using a neurogenetic approach, we investigated the association between the BDNF Val66Met polymorphism and self-reported empathy (Davis' Interpersonal Reactivity Index; IRI) in a sample of 110 young adults. Our results indicate that the BDNF genotype is significantly associated with the linear combination of the four facets of the IRI, one of the most widely used self-reported empathy questionnaire. Crucially, the effect of BDNF Val66Met goes beyond the variance explained by two polymorphisms of the oxytocin transporter gene previously associated with empathy and its neural underpinnings (OXTR rs53576 and rs2254298). These results represent the first evidence suggesting a link between the BDNF gene and self-reported empathy and warrant further studies of this polymorphism due to its potential clinical significance. PMID:26901829
Full Text Available Aim. Functional polymorphism ER22/23EK glucocorticoid receptor leads to reduction of its resistance and to increase in its sensitivity to the glucocorticoid that regulate the functioning of the axis hypothalamus - pituitary - adrenal glands. Disturbances in the regulation of this axis are observed in patients with psychiatric disorders. The aim of this study was to demonstrate the association ER22/23EK polymorphism with bipolar disorder and major depressive disorders.Methods. In the study 144 patients with unipolar disorders and 479 patients with bipolar disorder were included. Patients were diagnosed by two psychiatrists on the basis of medical records and interview based on SCID criteria (Structured Clinical Interview for DSM Disorders. The control group comprised 595 healthy subjects. As the research material peripheral blood was used, from which DNA was obtained. Genotyping was performed using PCR - RFLP method.Results. No association of ER22/23EK polymorphism with unipolar disorder or with bipolar disorder was found. GA genotype was not observed in any of the subjects.Conclusion. ER22/23EK functional polymorphism of the glucocorticoid receptor gene is not associated with unipolar and bipolar disorder.
Full Text Available Abstract Background Tribbles 3 (TRB3 affects insulin signalling by inhibiting insulin-stimulated Akt phosphorylation and subsequent activation. A single nucleotide polymorphism located in the second extron of the human TRB3 gene is thought to be associated with insulin resistance. The latter is a core abnormality in PCOS independent of obesity. The present study was designed to clarify the relationships of TRB3 Q84R polymorphism with PCOS in a Chinese women group. Methods A case-control study with two groups: PCOS group (n = 336 and control group of infertility women for tubal and/or male factor (n = 116 was performed. Genotyping of the TRB3 R84 variant was determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP. Results The frequency of genotype QQ in PCOS women was significantly lower, while genotype QR and RR were significantly higher than that in control group (p Conclusions TRB3 Q84R polymorphism is associated with obesity and especially glucose metabolism and not associated with polycystic ovary syndrome because of compositional characteristics of phenotype in Chinese PCOS women.
Guo, Liang; Tang, Ke; Quan, Zhengxue; Zhao, Zenghui; Jiang, Dianming
Functional polymorphisms of the osteoprotegerin (OPG) gene are known to be involved in bone mineral density and the development of osteoporosis; however, some conflicting results have been reported. The aim of this meta-analysis is to provide a relatively comprehensive assessment of the relationship between seven common OPG genetic polymorphisms (T149C, A163G, G209A, T245G, T950C, G1181C, and C1217T) and osteoporosis risk. A literature search for eligible studies published before August 1st, 2013 was conducted in PubMed, Embase, Web of Science, Cochrane Library, and CNKI (China National Knowledge Infrastructure) databases. Pooled odds ratios and their corresponding 95% confidence intervals were used to evaluate the strength of the association under fixed- or random-effect models according to a heterogeneity test. All analyses were performed using the STATA software, version 12.0. Fourteen case-control studies with a total of 2383 osteoporosis cases and 2280 healthy controls were included in this meta-analysis. Among the seven polymorphisms, A163G and G1181C revealed significant associations with osteoporosis risk. For A163G (rs3102735), the combined results showed that the G allele of the A163G polymorphism may be associated with an increased risk of osteoporosis. Stratified analyses showed that the magnitude of the effect was similar in Caucasian and postmenopausal woman subgroups. For G1181C (rs2073618), however, we found that individuals with the C allele of the G1181C polymorphism had a decreased risk of osteoporosis, especially in Asian and postmenopausal woman subgroups. In summary, this meta-analysis indicated that the G allele of the OPG A163G polymorphism might increase osteoporosis risk in Caucasians, whereas individuals with the C allele of the G1181C polymorphism had a decreased risk of osteoporosis, especially in Asians. Both of these effects were observed in postmenopausal women. These polymorphisms could probably be used with other genetic markers
Grobbee Diederick E
Full Text Available Abstract Background The association between anxiety and depression related traits and dyspepsia may reflect a common genetic predisposition. Furthermore, genetic factors may contribute to the risk of having increased visceral sensitivity, which has been implicated in dyspeptic symptom generation. Serotonin (5-HT modulates visceral sensitivity by its action on 5-HT3 receptors. Interestingly, a functional polymorphism in HTR3A, encoding the 5-HT3 receptor A subunit, has been reported to be associated with depression and anxiety related traits. A functional polymorphism in the serotonin transporter (5-HTT, which terminates serotonergic signalling, was also found associated with these psychiatric comorbidities and increased visceral sensitivity in irritable bowel syndrome, which coexistence is associated with higher dyspeptic symptom severity. We investigated the association between these functional polymorphisms and dyspeptic symptom severity. Methods Data from 592 unrelated, Caucasian, primary care patients with dyspepsia participating in a randomised clinical trial comparing step-up and step-down antacid drug treatment (The DIAMOND trial were analysed. Patients were genotyped for HTR3A c.-42C > T SNP and the 44 bp insertion/deletion polymorphism in the 5-HTT promoter (5-HTTLPR. Intensity of 8 dyspeptic symptoms at baseline was assessed using a validated questionnaire (0 = none; 6 = very severe. Sum score ≥20 was defined severe dyspepsia. Results HTR3A c.-42T allele carriers were more prevalent in patients with severe dyspepsia (OR 1.50, 95% CI 1.06-2.20. This association appeared to be stronger in females (OR 2.05, 95% CI 1.25-3.39 and patients homozygous for the long (L variant of the 5-HTTLPR genotype (OR 2.00, 95% CI 1.01-3.94. Females with 5-HTTLPR LL genotype showed the strongest association (OR = 3.50, 95% CI = 1.37-8.90. Conclusions The HTR3A c.-42T allele is associated with severe dyspeptic symptoms. The stronger association among
Park, Seo Yeon; Kim, Eun Joo; Cheon, Keun-Ah
Abstract Objectives: The purpose of this study is to examine the relationship between 5-HTTLPR polymorphism (44-bp insertion/deletion polymorphism of serotonin transporter gene) and methylphenidate (MPH) treatment response, as well as the association between the adverse events of MPH treatment and 5-HTTLPR polymorphism in children with attention-deficit/hyperactivity disorder (ADHD). Methods: A total of 114 children with ADHD (mean age 9.08 ± 1.94 years) were recruited from the child psychiat...
Yang, Bo; Heng, Liang; Du, Shuli; Hua YANG; Jin, Tianbo; Lang, Hongjuan; Li, Shanqu
Background Glioblastoma (GBM) is a highly invasive, aggressive, and incurable brain tumor. Genetic factors play important roles in GBM risk. The aim of this study was to elucidate the influence of gene polymorphism on GBM susceptibility. Material/Methods In this case-control study, we included 72 GBM patients and 320 healthy controls to analyze the association between 29 single-nucleotide polymorphisms and GBM cancer risk in the Chinese Han population. The single-nucleotide polymorphisms were...
Chen, Jian Huan; Chen, Haoyu; Huang, Shulan; Lin, Jianwei; Zheng, Yuqian; Xie, Mingliang; Lin, Wenjie; Pang, Chi Pui; ZHANG, MINGZHI
Purpose To investigate the association with ocular biometric parameters in myopia-associated single nucleotide polymorphisms (SNPs) of the gap junction protein delta 2 (GJD2), insulin-like growth factor-1 (IGF1) and hepatocyte growth factor (HGF) genes in two geographically different Chinese cohorts. Methods In 814 unrelated Han Chinese individuals aged above 50 years including 362 inland residents and 432 island dwellers, comprehensive ophthalmic examinations were performed. Three SNPs, incl...
Full Text Available Abstract Backgrounds Two SNPs in melatonin receptor 1B gene, rs10830963 and rs1387153 showed significant associations with fasting plasma glucose levels and the risk of Type 2 Diabetes Mellitus (T2DM in previous studies. Since T2DM and gestational diabetes mellitus (GDM share similar characteristics, we suspected that the two genetic polymorphisms in MTNR1B may be associated with GDM, and conducted association studies between the polymorphisms and the disease. Furthermore, we also examined genetic effects of the two polymorphisms with various diabetes-related phenotypes. Methods A total of 1,918 subjects (928 GDM patients and 990 controls were used for the study. Two MTNR1B polymorphisms were genotyped using TaqMan assay. The allele distributions of SNPs were evaluated by x2 models calculating odds ratios (ORs, 95% confidence intervals (CIs, and corresponding P values. Multiple regressions were used for association analyses of GDM-related traits. Finally, conditional analyses were also performed. Results We found significant associations between the two genetic variants and GDM, rs10830963, with a corrected P value of 0.0001, and rs1387153, with the corrected P value of 0.0008. In addition, we also found that the two SNPs were associated with various phenotypes such as homeostasis model assessment of beta-cell function and fasting glucose levels. Further conditional analyses results suggested that rs10830963 might be more likely functional in case/control analysis, although not clear in GDM-related phenotype analyses. Conclusion There have been studies that found associations between genetic variants of other genes and GDM, this is the first study that found significant associations between SNPs of MTNR1B and GDM. The genetic effects of two SNPs identified in this study would be helpful in understanding the insight of GDM and other diabetes-related disorders.
Full Text Available OBJECTIVE: Serum uric acid (SUA is a cardiovascular risk marker associated with inflammation. The serum amyloid A protein (SAA is an inflammatory factor and is associated with cardiovascular disease (CVD. However, the relationship between genetic polymorphisms of SAA and SUA levels has not been studied. The objective of this study was to investigate the association between SUA levels and SAA genetic polymorphisms. METHODS: All participants were selected from subjects participating in the Cardiovascular Risk Survey (CRS study. The single nucleotide polymorphism (SNP rs12218 of the SAA1 gene was genotyped by using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP method. The association of SUA levels with genotypes was assessed by using the general liner mode. RESULTS: The SNP rs12218 was associated with SUA levels by analyses of a dominate model (P = 0.002 and additive model (P = 0.005, and the difference remained significant after adjustment of sex, age, obesity, ethnicity, HDL-C, alcohol intake, smoking, and creatinine (P = 0.006 and P = 0.023, respectively. The TT genotype was associated with an increased SUA concentration of 39.34 mmol/L (95% confidence interval [CI], 3.61-75.06, P = 0.031 compared with the CC genotype, and the TT genotype was associated with an increased SUA concentration of 2.48 mmol/L (95% CI, 6.86-38.10; P = 0.005 compared with the CT genotype. CONCLUSIONS: The rs12218 SNP in the SAA1 gene was associated with SUA levels in Chinese subjects, indicating that carriers of the T allele of rs12218 have a high risk of hyperuricemia.
Apicella, Coren L.; Westberg, Lars
Background: Oxytocin (OXT) has been implicated in a suite of complex social behaviors including observed choices in economic laboratory experiments. However, actual studies of associations between oxytocin receptor (OXTR) gene variants and experimentally elicited social preferences are rare. Methodology/Principal Findings: We test hypotheses of associations between social preferences, as measured by behavior in two economic games, and 9 single nucleotide polymorphisms (SNPs) of the OXTR gene ...
Grubić, Z.; Žunec, R.; Kaštelan, M.; Čečuk-Jeličić, E.; Gruber, F; Kaštelan, A.
The purpose of the present study was to investigate polymorphism of HLA class II haplotypic associations (HLA-DRB1, -DQA1, -DQB1) and DQCAR alleles in 78 Croatian patients with psoriasis. Patients were divided into two groups according to a family history of disease and age of onset: type I (positive family history and early onset) and type II (negative family history and late onset). The difference in frequency of HLA class II haplotypic associations between type I patients an...
Park, Jin-Kyu; Kim, Mi Kyung; Choi, Bo Youl; Jung, Yusun; Song, Kyuyoung; Kim, Yu Mi; Shin, Jinho
Background Left ventricular hypertrophy (LVH) is a valid predictor for cardiovascular mortality and morbidity regardless of age, gender, and race. The HyperGEN study conducted a genome-wide association study and identified twelve single nucleotide polymorphisms (SNPs) associated with LVH. The aim of this study was to validate these candidate SNPs in the Korean population. Methods Among 1637 individuals from the Korean Multi-Rural Communities Cohort Study (MRCohort) of the Korean Genome Epidem...
Hua, Rui-Xi; Li, He-Ping; Liang, Yan-bing; Zhu, Jin-Hong; Zhang, Bing; Ye, Sheng; Dai, Qiang-Sheng; Xiong, Shi-Qiu; Gu, Yong; Sun, Xiang-Zhou
Background Poly (ADP-ribose) polymerase-1 (PARP-1) plays critical roles in the detection and repair of damaged DNA, as well as cell proliferation and death. Numerous studies have examined the associations between PARP1 Val762Ala (rs1136410 T>C) polymorphism and cancer susceptibility; nevertheless, the findings from different research groups remain controversial. Methods We searched literatures from MEDLINE, EMBASE and CBM pertaining to such associations, and then calculated pooled odds ratio ...
Balneek Singh Cheema
Full Text Available Background: Osteopontin (OPN C-443T promoter polymorphism has been shown as a genetic risk factor for diabetic nephropathy (DN in type 2 diabetic patients (T2D. Methods: In the present study we investigated the association of three functional promoter gene polymorphisms C-443T, delG-156G, and G-66T and their haplotypes with the risk of DN and estimated Glomerular Filtration Rate (eGFR in Asian Indians T2D patients using Real time PCR based Taqman assay. A total of 1165 T2D patients, belonging to two independently ascertained Indian Asian cohorts, were genotyped for three OPN promoter polymorphisms C-443T (rs11730582, delG-156G (rs17524488 and G-66T (rs28357094. Results: -156G allele and GG genotypes (delG-156G and haplotypes G-C-G and T-C-G (G-66T, C-443T, delG-156G were associated with decreased risk of DN and higher eGFR. Haplotype G-T-delG and T-T-delG (G-66T, C-443T, delG-156G were identified as risk haplotypes, as shown by lower eGFR. Conclusion: This is the first study to report an association of OPN promoter gene polymorphisms; G-66T and delG-156G and their haplotypes with DN in T2D. Our results suggest an association between OPN promoter gene polymorphisms and their haplotypes with DN.
Full Text Available Impulsivity is a personality trait of high impact and is connected with several types of maladaptive behavior and psychiatric diseases, such as attention deficit hyperactivity disorder, alcohol and drug abuse, as well as pathological gambling and mood disorders. Polymorphic variants of the SNAP-25 gene emerged as putative genetic components of impulsivity, as SNAP-25 protein plays an important role in the central nervous system, and its SNPs are associated with several psychiatric disorders. In this study we aimed to investigate if polymorphisms in the regulatory regions of the SNAP-25 gene are in association with normal variability of impulsivity. Genotypes and haplotypes of two polymorphisms in the promoter (rs6077690 and rs6039769 and two SNPs in the 3' UTR (rs3746544 and rs1051312 of the SNAP-25 gene were determined in a healthy Hungarian population (N = 901 using PCR-RFLP or real-time PCR in combination with sequence specific probes. Significant association was found between the T-T 3' UTR haplotype and impulsivity, whereas no association could be detected with genotypes or haplotypes of the promoter loci. According to sequence alignment, the polymorphisms in the 3' UTR of the gene alter the binding site of microRNA-641, which was analyzed by luciferase reporter system. It was observed that haplotypes altering one or two nucleotides in the binding site of the seed region of microRNA-641 significantly increased the amount of generated protein in vitro. These findings support the role of polymorphic SNAP-25 variants both at psychogenetic and molecular biological levels.
Vimaleswaran, Karani S; Franks, Paul W; Brage, Soren; Sardinha, Luis B; Andersen, Lars B; Wareham, Nicholas J; Ekelund, Ulf; Loos, Ruth J F
Estonian children (930 boys and 1,073 girls) from the European Youth Heart Study (EYHS), a school-based, cross-sectional study of pre- and early pubertal children. The association between the polymorphism and obesity traits was tested using additive and recessive models adjusted for age, age-group, gender...... this polymorphism with obesity traits. This polymorphism has been hypothesized to alter INSIG2 expression leading to inhibition of fatty acid and cholesterol synthesis. Hence, we investigated the association of the INSIG2 rs7566605 polymorphism with obesity- and lipid-related traits in Danish and.......24). Accordingly, the polymorphism was not associated with overweight (P = 0.87) or obesity (P = 0.34). We also did not find association with waist circumference (WC), sum of four skinfolds, or with total cholesterol, triglycerides, low-density lipoprotein, or high-density lipoprotein. There were no gender...
JiMing Bao; XianLu Song; YingQia Hong; HaiLi Zhu; Cui Li; Tao Zhang; Wei Chen; ShanChao Zhao; Qing Chen
Numerous studies have shown associations between the FOXO3Agene, encoding the forkhead box O3 transcription factor, and human or speciifcally male longevity. However, the associations of speciifc FOXO3A polymorphisms with longevity remain inconclusive. We performed a meta-analysis of existing studies to clarify these potential associations. A comprehensive search was conducted to identify studies of FOXO3A gene polymorphisms and longevity. Pooled odds ratios (ORs) and 95%conifdence intervals (CIs) were calculated by comparing the minor and major alleles. A total of seven articles reporting associations of FOXO3A polymorphisms with longevity were identiifed and included in this meta-analysis. These comprised 11 independent studies with 5241 cases and 5724 controls from different ethnic groups. rs2802292, rs2764264, rs13217795, rs1935949 and rs2802288 polymorphisms were associated with human longevity (OR=1.36, 95%CI=1.10-1.69, P=0.005;OR=1.20, 95%CI=1.04-1.37, P=0.01;OR=1.27, 95%CI=1.10-1.46, P=0.001;OR=1.14, 95%CI=1.01-1.27 and OR=1.24, 95%CI=1.07-1.43, P=0.003, respectively). Analysis stratiifed by gender indicated signiifcant associations between rs2802292, rs2764264 and rs13217795 and male longevity (OR=1.54, 95%CI=1.33-1.79, P<0.001;OR=1.38, 95%CI=1.15-1.66, P=0.001;and OR=1.39, 95%CI=1.15-1.67, P=0.001), but rs2802292, rs2764264 and rs1935949 were not linked to female longevity. Moreover, our study showed no association between rs2153960, rs7762395 or rs13220810 polymorphisms and longevity. In conclusion, this meta-analysis indicates a signiifcant association of ifve FOXO3Agene polymorphisms with longevity, with the effects of rs2802292 and rs2764264 being male-speciifc. Further investigations are required to conifrm these ifndings.
Hare, Lauren; Bernard, Pascal; Sánchez, Francisco J.; Baird, Paul N.; Vilain, Eric; Kennedy, Trudy; Harley, Vincent R.
Background There is a likely genetic component to transsexualism, and genes involved in sex steroidogenesis are good candidates. We explored the specific hypothesis that male-to-female transsexualism is associated with gene variants responsible for undermasculinization and/or feminization. Specifically, we assessed the role of disease-associated repeat length polymorphisms in the androgen receptor (AR), estrogen receptor β (ERβ), and aromatase (CYP19) genes. Methods Subject-control analysis included 112 male-to-female transsexuals and 258 non-transsexual males. Associations and interactions were investigated between CAG repeat length in the AR gene, CA repeat length in the ERβ gene, and TTTA repeat length in the CYP19 gene and male-to-female transsexualism. Results A significant association was identified between transsexualism and the AR allele, with transsexuals having longer AR repeat lengths than non-transsexual male control subjects (p = .04). No associations for transsexualism were evident in repeat lengths for CYP19 or ERβ genes. Individuals were then classified as short or long for each gene polymorphism on the basis of control median polymorphism lengths in order to further elucidate possible combined effects. No interaction associations between the three genes and transsexualism were identified. Conclusions This study provides evidence that male gender identity might be partly mediated through the androgen receptor. PMID:18962445
Full Text Available AIMS: Many studies have investigated the relationship between FTO gene polymorphism and polycystic ovary syndrome (PCOS susceptibility but revealed mixed results. In this study, we aimed to perform a meta-analysis to clarify this association. METHODS: Published literature from PubMed, Embase and CNKI was retrieved. Meta-analysis was performed to calculate pooled odds ratio (OR with 95% confidence interval (CI using the random- or fix- effects model. RESULTS: A total of 5 studies (4778 cases and 4272 controls were included in our meta-analysis. The results suggested that FTO rs9939609 polymorphism (or its proxy was marginally associated with PCOS risk after adjustment for body mass index (BMI (OR = 1.26; 95%CI: 1.02-1.55. However, the marginal association was not stable after sensitivity analysis. In the subgroup analysis by ethnicity, the association was significant in East Asians (OR = 1.43, 95%CI = 1.30-1.59 but not in Caucasians (OR = 1.04, 95%CI = 0.85-1.29. CONCLUSIONS: Our present meta-analysis indicated that FTO rs9939609 polymorphism (or its proxy might not be associated with risk of PCOS in overall population. However, in East Asians, there might be a direct association between FTO variant and PCOS risk, which is independent of BMI (adiposity.
Full Text Available Insulin resistance and obesity is influenced by the retinol binding protein 4 (RBP4 adipokine. This study aims to determine if genetic polymorphisms in RBP4 are associated with the risk of coronary artery disease (CAD in Chinese patients. RBP4 polymorphisms were analyzed by high resolution melting (HRM analysis in a case-control study of 392 unrelated CAD patients and 368 controls from China. The Gensini score was used to determine the severity of CAD. The genotypic and allelic frequencies of RBP4 single-nucleotide polymorphisms were evaluated for associations with CAD and severity of disease. The A allele frequency was significantly higher in CAD case groups compared to control groups (16.7% vs. 8.8% at the RBP4 rs7094671 locus. Compared to the G allele, this allele was associated with a higher risk of CAD (OR = 2.07 (1.50–2.84. Polymorphisms at rs7094671 were found to associate with CAD using either a dominant or recessive model (OR, 95% CI: 1.97, 1.38–2.81; 3.81, 1.53–9.51, respectively. Adjusting for sex, history of smoking, serum TC, TG, LDL-c, and HDL-c, the risk of CAD for carriers remained signiﬁcantly higher in both dominant and recessive models (OR, 95% CI: 1.68, 1.12–2.51; 2.74, 1.00–7.52, respectively. However, this SNP was not significantly associated with severity of CAD using angiographic scores in multivariable linear regression models (p = 0.373. The RBP4 rs7094671 SNP is associated with CAD; however, our results do not indicate that this locus is associated with clinical severity of CAD or the extent of coronary lesions.
Čepica, Stanislav; Bartenschlager, H.; Óvilo, C.; Zrůstová, J.; Masopust, Martin; Fernández, A.; López, A.; Knoll, Aleš; Rohrer, G. A.; Snelling, W. M.; Geldermann, H.
Roč. 41, č. 6 (2010), s. 646-651. ISSN 0268-9146 R&D Projects: GA ČR GA523/07/0353 Institutional research plan: CEZ:AV0Z50450515 Keywords : association study * carcass compositio * genetic mapping Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 2.203, year: 2010
Matrix Gla Protein (MGP) is a key regulator of vascular calcification. Genetic variation at the MGP locus could modulate the development of coronary artery calcification (CAC). We examined the cross-sectional association between MGP SNPs [rs1800802 (T-138C), rs1800801 (G-7A),and rs4236 (Ala102Thr)...
Hamid Reza Khorram Khorshid
Full Text Available Late-onset Alzheimer's disease (AD, a genetically heterogeneous neurodegenerative disorder, is the most common form of dementia in people over 65 years old. The role of vitamin D in neuropsychiatric and neurodegenerative disorders such as AD has been supported by epidemiologic investigations and animal models, as well. We examined the association of the vitamin D receptor (VDR gene polymorphisms and late-onset AD in an Iranian population.This study was performed in Tehran, Iran from 2007 to 2008. Totally, 145 AD patients and 162 age-matched unrelated healthy controls were included. The genotype and allele frequencies for the VDR polymorphisms, ApaI (G>T; rs7975232 and TaqI (C>T; rs731236, were determined in the case and control subjects PCR-RFLP analysis. Logistic regression analysis was performed to assess the effect of mutant genotype or allele in the study groups.The statistical analyses showed significant differences neither in genotype nor in allele frequencies of the ApaI and TaqI polymorphisms between the case and control groups.It seems that the ApaI and TaqI polymorphisms are not associated with the risk of late-onset AD in Iranian population.
Mauricio Venegas; Rodrigo A Villanueva; Katherine González; Javier Brahm
AIM: To analyze the association of three IL28B single nucleotide polymorphisms with response to therapy in Chilean patients infected with hepatitis C virus (HCV).((HHCV))).. METHODS: We studied two groups of patients with chronic HHCV infection ((genotype 1)), under standard combined treatment with pegylated interferon plus ribavirin. One group consisted of 50 patients with sustained virological response, whereas the second group consisted of 49 null responders. In order to analyze the IL28B single nucleotide polymorphisms rs12979860, rs12980275 and rs8099917, samples were used for polymerase chain reaction amplification, and the genotyping was performed by restriction fragment length polymorphism. RESULTS: The IL28B rs12979860 CC, rs12980275 AA and rs8099917 TT genotypes were much more frequently found in patients with sustained virological response compared to null responders ((38%, 44% and 50% vs 2%, 8.2% and 8.2%, respectively)). These differences were highly significant in all three cases (P < 0.0001)). CONCLUSION: The three IL28B polymorphisms studied are strongly associated with sustained virological response to therapy in Chilean patients with chronic HHCV ((genotype 1)).
Furusawa, Takuro; Naka, Izumi; Yamauchi, Taro; Natsuhara, Kazumi; Kimura, Ryosuke; Nakazawa, Minato; Ishida, Takafumi; Inaoka, Tsukasa; Matsumura, Yasuhiro; Ataka, Yuji; Nishida, Nao; Tsuchiya, Naoyuki; Ohtsuka, Ryutaro; Ohashi, Jun
Various Pacific Island populations have experienced a marked increase in the prevalence of obesity in past decades. This study examined the association of a promoter polymorphism of the leptin gene (LEP), G-2548A (rs7799039), and two non-synonymous single nucleotide polymorphisms of the leptin receptor gene (LEPR), K109R (rs1137100) and Q223R (rs1137101), with body weight, body mass index (BMI) and obesity (BMI > or = 30) in Pacific Islanders. A total of 745 Austronesian (AN)-speaking participants were analyzed after adjusting for age, gender, and population differences. The results revealed that carriers of the 223Q alleles of LEPR had significantly higher body weight (P = 0.0009) and BMI (P = 0.0022) than non-carriers (i.e., 223R homozygotes); furthermore, the 223Q carriers also had a signiWcantly higher risk of obesity in comparison to non-carriers (P = 0.0222). The other two polymorphisms, G-2548A and K109R, were associated with neither body weight, BMI, nor obesity. The 223Q allele was widely found among the AN-speaking study subjects, thus suggesting that the LEPR Q223R polymorphism is one of the factors contributing to the high prevalence of obesity in the Pacific Island populations. PMID:20183928
Guzmán-Fulgencio, María; Jiménez, José L; Jiménez-Sousa, María A; Bellón, José M; García-Álvarez, Mónica; Soriano, Vicente; Gijón-Vidaurreta, Paloma; Bernal-Morell, Enrique; Viciana, Pompeyo; Muñoz-Fernández, M Ángeles; Resino, Salvador
: Our aim was to explore the association among ACSM4 and PECI polymorphisms and AIDS progression in 454 HIV-infected patients never treated with antiretroviral drugs (146 long-term nonprogressors, 228 moderate progressors, and 80 rapid progressors). For ACSM4 polymorphisms, rs7137120 AA/AG and rs7961991 CC/CT genotypes had higher odds of having a rapid AIDS progression [odds ratio (OR) = 3.21; 95% of confidence interval (95% CI) = 1.26 to 8.16; P = 0.014 and OR = 3.60; 95% CI = 1.38 to 9.36; P = 0.009, respectively]. Additionally, the ACSM4 haplotype integrated for both rs7961991 A and rs7137120 C alleles had higher odds of having a rapid AIDS progression (OR = 2.85; 95% CI = 1.28 to 6.25; P = 0.010). For PECI polymorphisms, no significant associations were found. In conclusion, ACSM4 polymorphisms might play a significant role in AIDS progression. PMID:23982661
Interferon (IFN) lambda (IFN-λ or type III IFN) gene polymorphisms were discovered in the year 2009 to have a strong association with spontaneous and treatment-induced clearance of hepatitis C virus (HCV) infection in human hosts. This landmark discovery also brought renewed interest in type III IFN biology. After more than half a decade since this discovery, we now have reports that show that genetic association of IFNL gene polymorphisms in humans is not limited only to HCV infections but extends beyond, to include varied diseases such as non-alcoholic fatty liver disease, allergy and several other viral diseases including that caused by the human immunodeficiency virus. Notably, all these conditions have strong involvement of host innate immune responses. After the discovery of a deletion polymorphism that leads to the expression of a functional IFN-λ4 as the prime 'functional' variant, the relevance of other polymorphisms regulating the expression of IFN-λ3 is in doubt. Herein, I seek to critically address these issues and review the current literature to provide a framework to help further understanding of IFN-λ biology. PMID:27278127
Full Text Available Objectives. The −420C>G polymorphism located in the resistin gene (RETN promoter has recently been suggested to play a potential role in proinflammatory conditions and cardiovascular disease. This study investigated the association of the RETN promoter polymorphism with Kawasaki disease (KD and its clinical parameters in Chinese children. Methods. We compared patients with complete KD to incomplete KD children. Genotyping of the RETN promoter polymorphism was performed using MassARRAY system, and serum resistin levels were estimated using the sandwich enzyme immunoassay method. Results. There was no significant difference in RETN (−420C>G genotypes between KD and control groups. However, the frequency of the G allele was higher in iKD patients than in cKD children due to a significantly increased frequency of the GG genotypes. Serum levels of resistin were significantly higher in KD patients than in controls regardless of the presence of coronary artery lesions (CALs. Conclusion. The present findings suggest that while resistin may play a role in the pathogenesis of KD, there is no apparent association between CAL and the RETN (−420C>G gene polymorphism in KD children. However, the diagnosis of iKD is challenging but can be supported by the presence of the G allele and the GG genotypes.
Full Text Available The aim of the present study was to investigate the association of APOE, MTHFR and ACE polymorphisms with stroke in the Zambian population. We analyzed 41 stroke patients and 116 control subjects all of Zambian origin for associations between the genotype of the APOE, MTHFR and ACE polymorphisms and stroke. The APOE ε2ε4 genotype showed increased risk for hemorrhagic stroke (P<0.05 and also a high risk for ischemic stroke (P=0.05. There was complete absence of the APOE ε2ε2 and the MTHFR TT genotypes in the Zambian population. The difference between cases and controls was not significant for the other genetic variants when analyzed for relationship between stroke, stroke subtype and genotype. We show that genetic variation at the APOE locus affects susceptibility to stroke. No detectable association were observed for the MTHFR and ACE genotypes and stroke in the Zambian population.
Full Text Available Obesity and osteoporosis share common physiological factors, including the presence of atherosclerosis, a risk factor for cardiometabolic disease, as well as a common progenitor that differentiates into both adipocytes and osteoblasts. Among the 23 polymorphisms associated with bone mineral density (BMD in recent genome-wide association studies (GWASs, an Osterix polymorphism has been identified and associated with childhood obesity in girls. Therefore, we focused on elucidating polymorphisms associated with adulthood obesity in a sex-dependent manner among the previously published BMD-associated polymorphisms from GWASs. We performed 2 screenings of 18 BMD-associated polymorphisms for obesity-related traits in 2,362 adults aged >20 years. We excluded 13 polymorphisms showing deviations from Hardy-Weinberg equilibrium or no association with obesity-related traits (body mass index, waist circumference (WC, and waist-to-hip ratio. Among 5 selected polymorphisms (rs9594738 of RANKL, rs17066364 of NUFIP1, rs7227401 of OSBPL1A, and rs1856057 and rs2982573 of ESR1 analyzed, 2 polymorphisms (rs9594738 and rs17066364 were associated with obesity-related traits. We found sex-dependent associations such that the 4 polymorphisms (excluding rs9594738 of RANKL were associated with abdominal traits such as WC and waist-to-hip ratio only in men. In addition, when the combined genetic risk score (GRS for WC increase was calculated with 4 SNPs (rs9594738, rs17066364, rs7227401, and rs1856057 exhibiting similar trends for both sexes, the magnitude of the GRS effect for the WC increase was larger in men than in women (effect size = 0.856 cm, P = 0.0000452 for men; effect size = 0.598 cm, P = 0.00228 for women. In summary, we found 4 polymorphisms, previously related to osteoporosis, to be associated to obesity-related traits in a sex-dependent manner in Korean adults, particularly in men.
Pirie, Ailith; Guo, Qi; Kraft, Peter; Canisius, Sander; Eccles, Diana M; Rahman, Nazneen; Nevanlinna, Heli; Chen, Constance; Khan, Sofia; Tyrer, Jonathan; Bolla, Manjeet K; Wang, Qin; Dennis, Joe; Michailidou, Kyriaki; Lush, Michael
Funding This work was supported by the following grants. Higher level funding The COGS project was funded through a European Commission's Seventh Framework Programme grant (agreement number 223175 - HEALTH-F2-2009-223175). The Breast Cancer Association Consortium (BCAC) is funded by Cancer Research-UK (C1287/A10118 and C1287/A12014). Meetings of the BCAC have been funded by the European Union COST programme (BM0606). ELAN Program of the University Hospital Erlangen (BBCC). Pers...
McKean-Cowdin, Roberta; Barnholtz-Sloan, Jill; Inskip, Peter; Ruder, Avima; Butler, MaryAnn; Rajaraman, Preetha; Razavi, Pedram; Patoka, Joe; Wiencke, John; Bondy, Melissa; Wrensch, Margaret
A pooled analysis was conducted to examine the association between select variants in DNA repair genes and glioblastoma multiforme (GBM), the most common and deadliest form of adult brain tumors. Genetic data for approximately 1,000 GBM cases and 2,000 controls were combined from four centers in the United States that have conducted case-control studies of adult GBM including the National Cancer Institute, the National Institute for Occupational Safety and Health, the University of Texas M.D....
Wang, Hong; Zhang, Kun; Qin, Haifeng; Yang, Lin; Zhang, Liyu; Cao, Yanyan
To systematically evaluate the association between poly(ADP-ribose) polymerase 1 (PARP1) rs1136410 T>C and brain tumor risk, a meta-analysis has been carried out. We performed a meta-analysis of 2004 brain tumor patients and 2944 controls by use of STATA version 12.0 to determine whether the risk of brain tumors was associated with the genotypes or alleles of rs1136410 T>C. We found a significantly decreased risk (ranging from 0.18- to 0.16-fold) in the dominant model (OR = 0.84, 95 % CI = 0.75-0.95), the C vs. T model (OR = 0.82, 95 % CI = 0.74-0.91), and the CT vs. TT model (OR = 0.86, 95 % CI = 0.76-0.98). The same genetic models demonstrated noteworthy associations when analysis was restrained to glioma (OR = 0.85, 95 % CI = 0.75-0.96; OR = 0.83, 95 % CI = 0.74-0.92; OR = 0.87, 95 % CI = 0.76-0.99, respectively). This meta-analysis suggests that PARP1 rs1136410 T>C may play a significant role in the protection against the development of brain tumors and glioma. PMID:25911198
Full Text Available Tilapias are a group of species with a variable tolerance to high salinity, which are cultured worldwide in fresh, brackish and seawater. Prolactin I (PRL I is known as a key hormone in osmoregulatory physiological pathways. A previous study, conducted in a single family, reported on association between polymorphism in a repetitive element within the promoter of the PRL I gene and growth rate of tilapia in saline water. This study was aiming to further validate this association in a larger sample size, and was conducted in nine families over two consecutive breeding seasons. We have confirmed this association in the three F2 families of Oreochromis mossambicus × Oreochromis niloticus hybrids challenged in the first year. The same pattern of improved growth for genotypes with shorter alleles originating from the O. niloticus grand-parental fish, although O. mossambicus is considered to be a more salt tolerant species, was demonstrated. The effects accounted for 13–15% of the phenotypic variance for growth rate (P < 0.05. In the six families from the second spawning season there was no association between the gene polymorphism and the fish growth in saline water. No association was evident between the polymorphism in the PRL I promoter and the expression of the gene.
Full Text Available BACKGROUND: Xeroderma pigmentosum complementation group C gene (XPC is a key member of nucleotide excision repair pathway and plays an important role in human DNA repair system. It is reported that several common polymorphisms of XPC are associated with susceptibility to lung cancer. However, the conclusion is still elusive. METHOD: This meta-analysis was performed to determine the relationship between XPC polymorphisms (Lys939Gln, Ala499Val, and PAT and lung cancer risk. Published literatures were identified by searching online databases and reference lists of relevant studies. Odds ratios (ORs and 95% confidence intervals (CIs were calculated to estimate the association strength. Publication bias were detected by Egger's and Begg's test. RESULT: After strict screening, we identified 14 eligible studies in this meta-analysis, including 5647 lung cancer cases and 6908 controls. By pooling all eligible studies, we found that the homozygote Gln939Gln genotype was associated with a significantly increased risk of lung cancer in Asian population (GlnGln vs LysLys, OR=1.229, 95% CI: 1.000-1.510; GlnGln vs LysLys/LysGln, OR=1.257, 95% CI: 1.038-1.522. As for the PAT polymorphism, in Caucasian population, we found carriers of the -/- genotype were associated significantly reduced risk of lung cancer in homozygote comparison model (-/- vs +/+, OR=0.735, 95% CI: 0.567-0.952. CONCLUSION: In this meta-analysis we found that Gln939Gln genotype was associated with significantly increased risk of lung cancer in Asian population; the PAT -/- genotype significantly reduced susceptibility to lung cancer in Caucasian population; while the XPC Ala499Val polymorphism was not associated with lung cancer risk.
Zhang, Ying; Wu, Yuan-Yuan; Qiao, Fu-Yuan; Zeng, Wan-Jiang
p53 gene plays an important role in apoptosis, which is necessary for successful invasion of trophoblast cells. The change from an arginine (Arg) to a proline (Pro) at codon 72 can influence the biological activity of p53, which predisposes to an increased risk of recurrent spontaneous abortion (RSA). In order to investigate the association between p53 polymorphism at codon 72 and RSA, we conducted this meta-analysis. Pubmed, Embase and Web of science were used to identify the eligible studies. Odds ratio (OR) with 95% confidence interval (CI) was used to evaluate the strength of the association. Six studies containing 937 cases of RSA and 830 controls were included, and there was one study deviated from Hardy-Weinberg equilibrium (HWE). There was a significant association between p53 polymorphism at codon 72 and RSA in recessive model (Pro/Pro vs. Pro/Arg+Arg/Arg; OR=1.60, 95% CI: 1.14-2.24) and co-dominant model (Pro/Pro vs. Arg/Arg; OR=1.47, 95% CI: 1.02-2.12) whether the study that was deviated from HWE was eliminated or not. A significant association was observed in allelic model (Pro vs. Arg; OR=1.28, 95% CI: 1.04-1.57) after exclusion of the study that was deviated from HWE. No association was noted in recessive model (Pro/Pro+Pro/Arg vs. Arg/Arg; OR=1.05, 95% CI: 0.86-1.30) and co-dominant model (Pro/Arg vs. Arg/Arg; OR=0.96, 95% CI: 0.77-1.19). Subgroup analysis by ethnicity also indicated a significant association between p53 polymorphism at codon 72 and RSA in Caucasian group. No heterogeneity and publication bias were found. Our meta-analysis implied that p53 polymorphism at codon 72 carries high maternal risk of RSA. PMID:27376811
Sarmite Kupca; Tatjana Sjakste; Natalija Paramonova; Olga Sugoka; Irena Rinkuza; Ilva Trapina; Ilva Daugule; Sipols, Alfred J.; Ingrida Rumba-Rozenfelde
The aim of this study was to ascertain possible associations between childhood obesity, its anthropometric and clinical parameters, and three loci of proteasomal genes rs2277460 (PSMA6 c.-110C>A), rs1048990 (PSMA6 c.-8C>G), and rs2348071 (PSMA3 c. 543+138G>A) implicated in obesity-related diseases. Obese subjects included 94 otherwise healthy children in Latvia. Loci were genotyped and then analyzed using polymerase chain reactions, with results compared to those of 191 nonobese controls. PSM...
DONG-SHENG HU; JING XIE; DA-HAI YU; GUO-HENG XU; JIE LU; JIN-XIU YANG; CHUN-YANG LI; YAN-YAN LI
Objective To identify the association between PLIN 1237 polymorphism and obesity in Chinese Han adults. Methods A total of 994 adults (157 obese subjects, 322 overweight subjects, and 515 normal controls) were recruited from two rural communities. PLIN 1237 polymorphism was genotyped by polymerase chain reaction-restriction-fragment-length-polymorphism (PCR-RFLP). Association between PLIN polymorphisms and obesity status was estimated by ordinal logistic regression. Results The three genotypes of PLIN 1237 were detected with a percentage of 54.3%, 37.1%, and 8.6% in TT, TC, and CC genotypes, respectively. For the PLIN 1237 polymorphism locus, the frequency of alleles T and C was 0.73 and 0.27, respectively. The PLIN 1237 polymorphisms were in Hardy-Weinberg equilibrium. PLIN 1237 polymorphism was not associated with obesity. The odds ratio for overweight or obesity for the CC+TC genotype was 0.8 (0.4, 1.4) in women (P=0.4) and 0.6 (0.3, 1.3) in men (P=0.2) after adjustment for age, education, household income and alcohol consumption, smoking, and physical activity. Conclusion Chinese Han adults have a lower frequency of variant-allele C in PLIN 1237. PLIN 1237 T＞C polymorphism is not significantly associated with obesity in northern Chinese adults.
Full Text Available Nobuyuki Kanemaki,1 Akira Meguro,2 Takahiro Yamane,2 Masaki Takeuchi,2,3 Eiichi Okada,4 Yasuhito Iijima,5 Nobuhisa Mizuki2 1Veterinary Teaching Hospital, Azabu University, Sagamihara, 2Department of Ophthalmology and Visual Science, Yokohama City University Graduate School of Medicine, Yokohama, Kanagawa, Japan; 3Inflammatory Disease Section, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA; 4Okada Eye Clinic, 5Aoto Eye Clinic, Yokohama, Kanagawa, Japan Purpose: Many studies have investigated the relationship of paired box 6 (PAX6 gene polymorphisms with the risk of high myopia, but the results across studies remain inconsistent and ambiguous. In the present work, we investigated whether PAX6 polymorphisms are associated with high myopia in a Japanese population.Methods: A total of 1,585 Japanese patients with high myopia (spherical equivalent [SE] <-9.00 diopters [D] and 1,011 Japanese healthy controls (SE≥-1.00 D were recruited. To compare genotype frequencies between cases and controls, we genotyped five single nucleotide polymorphisms in the PAX6 gene that are reportedly associated with high/extreme myopia: rs662702, rs3026393, rs644242, rs3026390, and rs667773.Results: For rs662702, rs644242, and rs667773, odds ratios (ORs for their risk alleles tended to increase with the progression of SE and axial length in the additive and recessive models. Of these, rs644242 had the highest OR (2.56 in patients with SE<-15 D in both eyes in the recessive model. On the other hand, for rs3026393 and rs3026390, the ORs for their risk alleles tended to increase according to the progression of SE and axial length in the dominant model. Of the two, rs3026393 had the highest OR (2.32 in patients with SE<-15 D in both eyes in the dominant model. However, no significant associations were identified in this study.Conclusion: We found that these PAX6 single nucleotide polymorphisms were associated with an increased
Qie, Yunkai; Nian, Xuewu; Liu, Xuesen; Hu, Hailong; Zhang, Changwen; Xie, Linguo; Han, Ruifa; Wu, Changli; Xu, Yong
Objective Insulin-like growth factor-binding protein-3 (IGFBP3) is the major protein that binds with insulin-like growth factor-1 (IGF-1) and is considered to be involved in the development and progression of various cancers. We aimed to examine the association between prostate cancer (PCa) and the IGFBP3 gene-202A/C polymorphism. Methods A comprehensive search within PubMed, EMBASE, and Cochrane Library was conducted to identify all case–control studies up to October 30, 2015, for a meta-analysis. Pooled odds ratios (ORs) and the 95% confidence intervals (CIs) were calculated using the fixed or random effects model. Results Eighteen studies including 10,538 cases and 10,078 controls were identified. Overall, the CC genotype of IGFBP3-202A/C polymorphism was associated with increased risk of PCa in homozygote comparison (CC vs AA − OR =1.16, 95% CI: 1.08–1.25) and in recessive model (CC vs AA+AC − OR =1.11, 95% CI: 1.04–1.17). In dominant model, the CC/AC genotypes also implicated an increased risk of PCa (CC+AC vs AA − OR =1.11, 95% CI: 1.05–1.19). The C allele of IGFBP3-202A/C polymorphism was the risk allele for PCa relative to the A allele (OR =1.09, 95% CI: 1.05–1.14). Further stratification analysis revealed that the association between –202A/C polymorphism and PCa risk among Caucasians, but not in other ethnicities, was statistically significant (recessive model, OR =1.10, 95% CI: 1.02–1.19). In addition, the IGFBP3-202A/C polymorphism was associated with PCa risk in both population-based and hospital-based studies in homozygote comparison, recessive model, and allele model. Conclusion Our meta-analysis indicates that the IGFBP3-202A/C polymorphism is associated with the risk of PCa, particularly in Caucasians, with the C allele being the risk allele for PCa. PMID:27462171
Autism (MIM 209850) is a heterogeneous neurodevelopmental disease that manifests within the first 3 years of life. Numerous articles reported that dysfunctional folate-methionine pathway enzymes may play an important role in the pathophysiology of autism. Methylenetetrahydrofolate reductase (MTHFR) is a critical enzyme of this pathway and MTHFR C677T polymorphism reported as risk factor for autism in several case control studies. However, controversial reports were also published. Hence the present meta-analysis was designed to investigate the relationship of the MTHFR C677T polymorphism with the risk of autism. Electronic databases were searched for case control studies with following search terms - 'MTHFR', 'C677T', in combination with 'Autism'. Pooled OR with its corresponding 95 % CI was calculated and used as association measure to investigate the association between MTHFR C677T polymorphism and risk of autism. Total of thirteen studies were found suitable for the inclusion in the present meta-analysis, which comprises 1978 cases and 7257 controls. Meta-analysis using all four genetic models showed significant association between C677T polymorphism and autism (ORTvs.C = 1.48; 95 % CI: 1.18-1.86; P = 0.0007; ORTT + CT vs. CC = 1.70, 95 % CI = 0.96-2.9, p = 0.05; ORTT vs. CC = 1.84, 95 % CI = 1.12-3.02, p = 0.02; ORCT vs.CC = 1.60, 95 % CI = 1.2-2.1, p = 0.003; ORTT vs.CT+CC = 1.5, 95 % CI = 1.02-2.2, p = 0.03). In total 13 studies, 9 studies were from Caucasian population and 4 studies were from Asian population. The association between C677T polymorphism and autism was significant in Caucasian (ORTvs.C = 1.43; 95 % CI = 1.1-1.87; p = 0.009) and Asian population (ORTvs.C = 1.68; 95 % CI = 1.02-2.77; p = 0.04) using allele contrast model. In conclusion, present meta-analysis strongly suggested a significant association of the MTHFR C677T polymorphism with autism. PMID:26956130
Nishank, Sudhansu Sekhar; Singh, Mendi Prema Shyam Sunder; Yadav, Rajiv; Gupta, Rasik Bihari; Gadge, Vijay Sadashiv; Gwal, Anil
Patients with sickle cell disease (SCD) produce significantly low levels of plasma nitric oxide (NO) during acute vaso-occlusive crisis. In transgenic sickle cell mice, NO synthesized by endothelial nitric oxide synthase (eNOS) enzyme of vascular endothelial cells has been found to protect the mice from vaso-occlusive events. Therefore, the present study aims to explore possible association of eNOS gene polymorphism as a potential genetic modifier in SCD patients. A case control study involving 150 SCD patients and age- and ethnicity-matched 150 healthy controls were genotyped by PCR-restriction fragment length polymorphism techniques for three important eNOS gene polymorphisms-eNOS 4a/b, eNOS 894G>T and eNOS -786T>C. It was observed that SCD patients had significantly higher frequencies of mutant alleles besides heterozygous and homozygous mutant genotypes of these three eNOS gene polymorphisms and low levels of plasma nitrite (NO2) as compared with control groups. The SCD severe group had significantly lower levels of plasma NO2 and higher frequencies of mutant alleles of these three SNPs of eNOS gene in contrast to the SCD mild group of patients. Haplotype analysis revealed that frequencies of one mutant haplotype '4a-T-C' (alleles in order of eNOS 4a/b, eNOS 894G>T and eNOS -786T>C) were significantly high in the severe SCD patients (Phaplotype '4b-G-T' was found to be significantly high (P<0.0001) in the SCD mild patients, which indicates that eNOS gene polymorphisms are associated with SCD patients in India and may act as a genetic modifier of the phenotypic variation of SCD patients. PMID:24088668
Full Text Available Type 2 diabetes (T2D is one of the most frequent mortality causes in western countries, with rapidly increasing prevalence. Anti-diabetic drugs are the first therapeutic approach, although many patients develop drug resistance. Most drug responsiveness variability can be explained by genetic causes. Inter-individual variability is principally due to single nucleotide polymorphisms, and differential drug responsiveness has been correlated to alteration in genes involved in drug metabolism (CYP2C9 or insulin signaling (IRS1, ABCC8, KCNJ11 and PPARG. However, most genome-wide association studies did not provide clues about the contribution of DNA variations to impaired drug responsiveness. Thus, characterizing T2D drug responsiveness variants is needed to guide clinicians toward tailored therapeutic approaches. Here, we extensively investigated polymorphisms associated with altered drug response in T2D, predicting their effects in silico. Combining different computational approaches, we focused on the expression pattern of genes correlated to drug resistance and inferred evolutionary conservation of polymorphic residues, computationally predicting the biochemical properties of polymorphic proteins. Using RNA-Sequencing followed by targeted validation, we identified and experimentally confirmed that two nucleotide variations in the CAPN10 gene—currently annotated as intronic—fall within two new transcripts in this locus. Additionally, we found that a Single Nucleotide Polymorphism (SNP, currently reported as intergenic, maps to the intron of a new transcript, harboring CAPN10 and GPR35 genes, which undergoes non-sense mediated decay. Finally, we analyzed variants that fall into non-coding regulatory regions of yet underestimated functional significance, predicting that some of them can potentially affect gene expression and/or post-transcriptional regulation of mRNAs affecting the splicing.
Osteoporosis is a common disease of the elderly, in which genetic and clinical factors contribute to the disease phenotype. Since the production of interleukin-1 (IL-1) has been implicated in the bone mass and skeletal disorders, we investigated whether IL-1 system gene polymorphisms are associated with the pathogenesis of osteoporosis in postmenopausal Taiwanese women.Osteoporosis is diagnosed by dual-energy x-ray absorptiometry, which measures bone mineral density (BMD) at multiple skeletal sites. We studied the IL-1a (-889C/T), IL-1 (-511C/T) and the 86 base pair variable number tandem repeat (VNTR) in intron 2 of the IL-1 receptor antagonist (IL-1ra) gene in 117 postmenopausal women with osteoporosis and 135 control subjects without a history of symptomatic osteoporosis. These gene polymorphisms were analyzed by polymerase chain reaction and restriction fragment length polymerase. Blood sugar and other risk factors were also determined.The frequencies of IL-1 (-511C/T) genotypes (P=.022, odds ratio=1.972) and alleles (P=.02, odds ratio=2.909) showed a statistically significant difference between the two groups. However, we did not find any statistically significant difference in IL-1 and IL-1ra polymorphisms (P>.05). We also observed a positive relationship between osteoporosis and cholesterol and a weak inverse relationship between blood sugar and osteoporosis in postmenopausal women.These experimental results suggest that the pathogenesis of osteoporosis is associated with IL-1 (-511C/T) polymorphism in postmenopausal women. This polymorphism is an independent risk factor for osteoporosis (Author).
Full Text Available TERT is of great importance in cancer initiation and progression. Many studies have demonstrated the TERT polymorphisms as risk factors for many cancer types, including lung cancer. However, the impacts of TERT variants on cancer progression and treatment efficacy have remained controversial. This study aimed to investigate the association of TERT polymorphisms with clinical outcome of advanced non-small cell lung cancer (NSCLC patients receiving first-line platinum-based chemotherapy, including response rate, clinical benefit, progression-free survival (PFS, overall survival (OS, and grade 3 or 4 toxicity. Seven polymorphisms of TERT were assessed, and a total of 1004 inoperable advanced NSCLC patients treated with platinum-based chemotherapy were enrolled. It is exhibited that the variant heterozygote of rs4975605 showed significant association with a low rate of clinical benefit, and displayed a much stronger effect in never-smoking female subset, leading to the clinical benefit rate decreased from 82.9% (C/C genotype to 56.4% (C/A genotype; adjusted OR, 3.58; P=1.40×10(-4. It is also observed that the polymorphism rs2736109 showed significant correlation with PFS (log-rank P=0.023. In age > 58 subgroup, patients carrying the heterozygous genotype had a longer median PFS than those carrying the wild-type genotypes (P=0.002. The results from the current study, for the first time to our knowledge, provide suggestive evidence of an effect of TERT polymorphisms on disease progression variability among Chinese patients with platinum-treated advanced NSCLC.
Liu, Jie; Liu, Juan; Ni, Jing; Leng, Rui Xue; Pan, Hai Feng; Ye, Dong Qing
Recent evidence has demonstrated that UBASH3A gene was associated with multiple autoimmune diseases. The aim of this study was to explore the association between UBASH3A gene single-nucleotide polymorphisms (SNPs) and systemic lupus erythematosus (SLE) in a Chinese Han population. Four UBASH3A polymorphisms (rs11203203, rs3788013, rs2277798, and rs1893592) were genotyped using the Fluidigm 192.24 Dynamic Array™ Integrated Fluidic Circuit (IFC). Data were analyzed by SPSS 11.5 software. A total of 792 SLE patients and 777 healthy controls were included in this study. The CC genotype and C allele of rs3788013 polymorphism were more frequent in the patient group than in controls (OR=1.583, 95% CI=1.095-2.287; OR=1.258, 95% CI=1.083-1.461, respectively). We also found a statistical significance under the recessive model (OR=1.298, 95% CI=1.049-1.607, p=0.017). The frequency of variant genotype AC of rs3788013 was associated with the phenotype of vasculitis (p=0.012). A statistically significant association was observed between UBASH3A rs1893592 C allele and skin rash, oral ulcer and arthritis (p0.05). The findings suggest that UBASH3A gene might contribute to SLE susceptibility and influence the clinical phenotype of the disease. Further studies are necessary to elucidate the exact role of UBASH3A gene in the pathogenesis of SLE. PMID:25843625
ZUO Peng-xiang; WU Han-rong; LI Zeng-chun; CAO Xu-dong; PANG Li-juan; YANG Lan; LIU Fan; ZHAO Feng
Background Genetic association studies on populations of European origin have identified the DCDC2 gene as a susceptibility locus for developmental dyslexia.Here,we sought to investigate the association of DCDC2 polymorphisms with developmental dyslexia in children of Han Chinese origin.Methods We undertook a case-control genetic association study on 76 dyslexic children and 79 non-dyslexic matched controls.We isolated DNA from oral mucosal cell samples and genotyped two DCDC2 coding-sequence single nucleotide polymorphisms,rs2274305 and rs6456593,in each sample using SNaPshot single nucleotide extension.We compared the allele and genotype frequencies between the groups using the X2 test and analyzed the relationship between dyslexia and the polymorphism at both loci using unconditional logistic regression.We also predicted haplotypes and compared their frequencies between the two groups.Results The differences in the genotype distribution and the allelic genes of the two single nucleotide luci of the DCDC2 gene,rs2274305 and rs6456593,between the two dyslexic and non-dyslexic groups were statistically meaningless (P ＞0.05).The differences in the haplotype distributions of the DCDC2 gene between the dyslexic and normal group were statistically meaningless (P ＞0.05).Conclusion The DCDC2 gene may not be a susceptibility factor for developmental dyslexia among the Han Chinese.However,methodological issues may have prevented the detection of oositive associations.
Zhao, Hua; Chen, Yun; Zhang, Bao-ping; Zuo, Peng-xiang
The gene KIAA0319 has been reported to be associated with developmental dyslexia (DD) in previous studies, although the results have not always been consistent. However, few studies have been conducted in Uyghur populations. In the present study, we aimed to investigate the association of KIAA0319 polymorphisms and DD in individuals of Uyghurian descent. We used a custom-by-design 48-Plex SNPscan Kit to genotype 18 single-nucleotide polymorphisms (SNPs) of KIAA0319 in a group of 196 children with dyslexia and 196 controls of Uyghur descent aged 8–12 years. As a result, 7 SNPs (Pmin=0.001) of KIAA0319 had nominal significant differences between the cases and controls under specific genotypic models. The two SNPs rs6935076 (P=0.020 under dominant model; P=0.028 under additive model) and rs3756821 (P=0.021 under additive model) remained significantly associated with dyslexia after Bonferroni correction. Linkage disequilibrium analysis showed three blocks within KIAA0319, and only a 10-SNP haplotype in block 3 was present at significantly different frequencies in the dyslexic children and controls. This study indicated that genetic polymorphisms of KIAA0319 are associated with an increased risk of DD in the Uyghur population. PMID:27098879
Full Text Available Single nucleotide polymorphisms (SNPs are important markers which can be used in association studies searching for susceptible genes of complex diseases. High-throughput methods are needed for SNP genotyping in a large number of samples. In this study, we applied polyacrylamide gel-based microarray combined with dual-color hybridization for association study of four BDNF polymorphisms with autism. All the SNPs in both patients and controls could be analyzed quickly and correctly. Among four SNPs, only C270T polymorphism showed significant differences in the frequency of the allele (χ2 = 7.809, p = 0.005 and genotype (χ2 = 7.800, p = 0.020. In the haplotype association analysis, there was significant difference in global haplotype distribution between the groups (χ2 = 28.19，p = 3.44e-005. We suggest that BDNF has a possible role in the pathogenesis of autism. The study also show that the polyacrylamide gel-based microarray combined with dual-color hybridization is a rapid, simple and high-throughput method for SNPs genotyping, and can be used for association study of susceptible gene with disorders in large samples.
Full Text Available Background& Objective: Host resistance towards Leishmania infection is mediated by cellular immune responses leading to macrophage activation and parasite killing. According to the important role of IL-13 in the defense against visceral leishmaniasis (VL and the known effect of the IL-13 gene polymorphisms on its production, the aim of this study was to investigate the probable relationship between IL-13 gene polymorphisms and susceptibility to VL. Materials & Methods: The patient group included 52 patients who had suffered from VL infection and the control group consisted of 104 non-relative healthy people from the same endemic areas the patients were from (southern part of Fars Province. IL-13 (position -1512 A/C gene polymorphism was determined by polymerase chain reaction-restricted fragment length polymorphism (PCR-RFLP. Results: There was no significant association between the frequencies of IL-13 (-1512 alleles and genotypes in the patients with VL compared to the thenormal population. Conclusion: This study indicated that the IL-13 (position -1512 A/C genotypes cannot be considered as a genetic susceptibility factor for leishmaniasis.
Full Text Available Abstract Background Recent research shows that polycystic ovary syndrome (PCOS may have an association with low-grade chronic inflammation, and that PCOS may induce an increase in serum interleukin-18 (IL-18 levels. Methods To investigate the polymorphisms of the IL-18 gene promoters with PCOS, two single nucleotide polymorphisms (SNPs in the promoter of the IL-18 gene (at positions -607C/A and -137G/C in 118 Chinese women with PCOS and 79 controls were evaluated using polymerase chain reaction (PCR. Results No significant differences were found in the genotype distribution, allele frequency and haplotype frequency between the PCOS and control groups. Further analysis demonstrated a relationship between IL-18 gene promoter polymorphisms and PCOS insulin resistance (IR. Regarding the -137 allele frequency, G and C allele frequencies were 93.5% and 6.5%, respectively, in the PCOS with IR patients; G and C allele frequencies were 85.4% and 14.6%, respectively, in PCOS patients without IR (chi2 = 3.601, P = 0.048. Conclusions The presence of a polymorphism in the IL-18 gene was found to have no correlation with the occurrence of PCOS. Carriage of the C allele at position -137 in the promoter of the IL-18 gene may play a protective role from the development of PCOS IR.
Full Text Available Several asthma susceptibility loci, including a region containing the vitamin D receptor (VDR gene located at chromosome 12q, have been identified using genome-wide screens. Our aim is to investigate the association between single nucleotide polymorphisms (SNPs in VDR gene and asthma. One hundred one asthma patients and 206 healthy controls were enrolled in this study. Genotypes were determined using a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP strategy and DNA sequencing. The results showed that there was no significant differences in the genotype and allele frequencies of Fok I and Bsm I polymorphisms between asthma patients and the controls in the Chinese Hans (For Fok I: OR = 1.15, 95% CI: 0.82-1.60; for Bsm I: OR = 1.44, 95% CI: 0.87-2.38.It is suggested that Fok I and Bsm I polymorphisms of VDR gene may not significantly contribute to the development of asthma in the Chinese Hans.
JieTang; ChengZhou; Zhi-JunZhang; Shu-SenZheng
BACKGROUND: Autoimmune hepatitis is a chronic, generally progressive inflammatory disorder of the liver, of which the cause is unclear. It was demonstrated that genetic factors are involved in its pathogenesis. Previous studies showed that human leukocyte antigen in the major histocompatibility complex (MHC) is associated with susceptibility to autoimmune hepatitis. Current genome scanning studies suggest that genes outside the MHC also play a critical role in autoimmune disorders. This article focuses on our current understanding of the polymorphisms of these genes and their roles in the pathogenesis of autoimmune hepatitis. DATA SOURCES: Studies were identified by searching MEDLINE and PubMed for articles using the keywords autoimmune hepatitis, polymorphism, CTLA-4, Fas, TNF-α, TGF-β1, TBX21 and VDR up to May 2011. Additional papers were identified by a manual search of the references from key articles. RESULTS: According to the case-control studies on genetic polymorphisms, at least six genes (CTLA-4, Fas, TNF-α, TGF-β1, TBX21 and VDR) are involved in autoimmune hepatitis besides HLA. So far, there has been no agreement about gene susceptibility and the actual clinical significance of these genes is still controversial. CONCLUSION: Studies on gene polymorphisms outside the MHC and knowledge of genetic predispositions for autoimmune hepatitis may not only elucidate pathogenic mechanisms, but also provide new targets for therapy in the future.
Ma, Fang; Yang, Yu; Li, XiangWei; Zhou, Feng; Gao, Cong; Li, Mufei; Gao, Lei
Background Genetic polymorphism is suggested to be associated with human physical performance. The angiotensin I-converting enzyme insertion/deletion (ACE I/D) polymorphism and the α-actinin-3 gene (ACTN3) R577X polymorphism have been most widely studied for such association analysis. However, the findings are frequently heterogeneous. We aim to summarize the associations of ACE I/D and ACTN3 R577X with sport performance by means of meta-analysis. Methods We systematically reviewed and quanti...
Full Text Available Obsessive-compulsive disorder (OCD is a prevalent psychiatric disorder of unknown etiology. However, there is some evidence that the immune system may play an important role in its pathogenesis. In the present study, two polymorphisms (rs1800795 and rs361525 in the promoter region of the cytokine tumor necrosis factor-alpha (TNFA gene were genotyped in 183 OCD patients and in 249 healthy controls. The statistical tests were performed using the PLINK® software. We found that the A allele of the TNFA rs361525 polymorphism was significantly associated with OCD subjects, according to the allelic χ² association test (p=0.007. The presence of genetic markers, such as inflammatory cytokines genes linked to OCD, may represent additional evidence supporting the role of the immune system in its pathogenesis.
Chang-shun ZHANG; Zheng TAN; Lan YU; Sheng-nan WU; Ying HE; Niu-fan GU; Guo-yin FENG; Lin HE
AIM: To investigate the correlation between single nucleotide polymorphisms (SNPs) of functional candidate gene Prodynorphin (PDYN) and schizophrenia. METHODS: SNPs in the promoter and exon regions of PDYN were screened and genotyped for association study in a cohort of Chinese Han schizophrenia cases and controls. RESULTS:Two SNPs PDYN-1576C＞T and PDYN-946C＞G were identified in the promoter region but PDYN-946C＞G showed significant differences of allele distribution (x2=6.15, P=0.013) and genotype distribution (x2=6.87, P=0.032) between schizophrenic and control subjects. CONCLUSION: PDYN-946C＞G polymorphism demonstrated an association with population susceptibility to schizophrenia (P＜0.05).
Chibo Liu, Bo Xi
Full Text Available Background: The GRK4 and EMILIN1 genes have been suggested to be involved in the development of hypertension. However, the results have been inconsistent. In this study, a meta-analysis was performed to clarify the associations of polymorphisms in the GRK4 and EMILIN1 genes with hypertension risk.Methods: Published literature from PubMed and Embase databases were retrieved. Pooled odds ratios (ORs with 95% confidence intervals (CIs were calculated using fixed- or random-effects model.Results: Five studies for polymorphisms in the GRK4 gene and five studies for polymorphisms in the EMILIN1 gene were identified. The results suggested that rs1801058 polymorphism in the GRK4 gene was inversely associated with hypertension among East Asians (TT vs. CC: OR=0.39, 95%CI 0.28-0.55 and positively associated with hypertension among Europeans (TT vs. CC: OR= 2.38, 95%CI 1.38-4.10. Rs2960306 polymorphism in the GRK4 gene was significantly associated with hypertension among Europeans (TT vs. GG: OR=1.92, 95%CI 1.13-3.27. The significant associations were also observed for rs2011616 and rs2304682 polymorphisms in the EMILIN1 gene among Japanese (rs2011616: AA vs. GG: OR=0.38, 95%CI 0.18-0.82; rs2304682: GG vs. CC: OR=0.37, 95%CI 0.17-0.81 but not among Chinese.Conclusions: This meta-analysis suggested that rs1801058 polymorphism in the GRK4 gene was associated with hypertension in East Asians and Europeans. The significant association was also found for rs2960306 polymorphism in the GRK4 gene among Europeans. In addition, there were significant associations of rs2011616 and rs2304682 polymorphisms in the EMILIN1gene with hypertension among Japanese.
M. Yu. Krylov
Full Text Available Interleukin-1β (IL-1β is a potential stimulant of bone resorption. IL-1β receptor antagonist (IL-1RA is a natural inhibitor of the biological effects of IL-1β.Objective: to study the frequency distribution of polymorphisms in the IL-1β and IL-1RA genes and their association with bone mineral density (BMD in women with primary osteoporosis (OP.Subjects and methods. The distribution of genotype frequency of IL-1β (-511C/T polymorphism and that of IL-1RA 511C/T polymorphism that is associated with the number of variable tandem repeats (VTR, were investigated in 254 women with OP and 214 healthy women.Results and discussion. IL-1β (-511C/T genotype carriers were encountered somewhat more frequently among the patients with OP (53.0% than in the control group (43.4%; however, the differences were insignificant. In these carriers, the risk of OP was 1.5-fold higher than that in those of other genotypes (odds ratio, 1.49; confidence interval, 1.02–2.18; p = 0.041. The patients who were IL-1β T allele (CT- and TT-genotype carriers had a significantly lower spine (LI–IV BMD than those who had not this allele (CC-genotype; p = 0.011. The patients and the controls showed no differences in the frequency distribution of IL-1RA gene polymorphism associated with the number of VTR. In the OP group, the carriers of the rare genotype A1A3 in the IL-1RA gene (3.1% had significantly higher femoral neck BMD (0.698±0.064 g/cm2 than those of the А1А1, А1А2 and А2А2 genotypes (0.613±0.078; 0.607±0.082. and 0.615±0.064 g/cm2; р = 0.003, р = 0.003, and р = 0.002, respectively.Conclusion. IL-1β (-511C/T polymorphism is associated with lower spine BMD and IL-1RA A1A3 genotype polymorphism is related to higher femoral neck BMD.
Full Text Available Abstract Background Previous studies suggested that genetic polymorphisms in the epidermal growth factor receptor (EGFR gene had been implicated in the susceptibility to some tumors and inflammatory diseases. EGFR has been recently implicated in vascular pathophysiological processes associated with excessive remodeling and atherosclerosis. Acute coronary syndrome (ACS is a clinical manifestation of preceding atherosclerosis. Our purpose was to investigate the association of the EGFR polymorphism with the risk of ACS. In this context, we analyzed the HER-1 R497K and EGFR intron 1 (CAn repeat polymorphisms in 191 patients with ACS and 210 age- and sex-matched controls in a Chinese population, using a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP strategy and direct sequencing. Results There were significant differences in the genotype and allele distribution of R497K polymorphism of the EGFR gene between cases and controls. The Lys allele had a significantly increased risk of ACS compared with the Arg allele (adjusted OR = 1.49, 95% CI: 1.12–1.98, adjusted P = 0.006. However, no significant relationship between the number of (CAn repeats of EGFR intron 1 (both alleles P = 0.911. Considering these two polymorphisms together, there was no statistically significant difference between the two groups. Conclusion R497K polymorphism of the EGFR gene is significantly associated with the risk of ACS. Our data suggests that R497K polymorphism may be used as a genetic susceptibility marker of the ACS.
Coppedè, Fabio; Mancuso, Michelangelo; Lo Gerfo, Annalisa; Carlesi, Cecilia; Piazza, Selina; Rocchi, Anna; Petrozzi, Lucia; Nesti, Claudia; Micheli, Dario; Bacci, Andrea; Migliore, Lucia; Murri, Luigi; Siciliano, Gabriele
Amyotropic lateral sclerosis (ALS) is a fatal and progressive neurodegenerative disease causing the loss of motoneurons of the brain and the spinal cord. The etiology of ALS is still uncertain, but males are at increased risk for the disease than females. Several studies have suggested that motoneurons in ALS might be subjected to the double insult of increased DNA oxidative damage and deficiencies in DNA repair systems. Particularly, increased levels of 8-oxoguanine and impairments of the DNA base excision repair system have been observed in neurons of ALS patients. There is evidence that the Ser326Cys polymorphism of the human 8-oxoguanine DNA glycosylase 1 (hOGG1) gene is associated with a reduced DNA repair activity. To evaluate the role of the hOGG1 Ser326Cys polymorphism in sporadic ALS (sALS), we screened 136 patients and 129 matched controls. In the total population, we observed association between both the Cys326 allele (p=0.02) and the combined Ser326Cys+Cys326Cys genotype (OR=1.65, 95% CI=1.06-2.88) and increased risk of disease. After stratification by gender, the Cys326 allele (p=0.01), both the Ser326Cys genotype (OR=2.14, 95% CI=1.09-4.19) and the combined Ser326Cys+Cys326Cys genotype (OR=2.15, 95% CI=1.16-4.01) were associated with sALS risk only in males. No significant association between the Ser326Cys polymorphism and disease phenotype, including age and site of onset and disease progression, was observed. Present results suggest a possible involvement of the hOGG1 Ser326Cys polymorphism in sALS pathogenesis. PMID:17531381
Hamid Reza Khorram Khorshid; Elnaz Gozalpour; Kioomars Saliminejad; Masood Karimloo; Mina Ohadi; Koorosh Kamali
Abstract Background Late-onset Alzheimer’s disease (AD), a genetically heterogeneous neurodegenerative disorder, is the most common form of dementia in people over 65 years old. The role of vitamin D in neuropsychiatric and neurodegenerative disorders such as AD has been supported by epidemiologic investigations and animal models, as well. We examined the association of the vitamin D receptor (VDR) gene polymorphisms and late-onset AD in an Iranian population. Methods This study was performed...
Dr Nesma Gamal Elsheikh*, Professor Motassem Salah Amer, Assistant Professor Mohamed Shawaky Khater, Professor Randa Reda Mabrouk, Professor Tarek Khairy Abd Eldayam
Aim: Study association between Apo E polymorphism and development of heart failure among diabetic patients. Material and methods: case control study conducted on 90 elderly participants and they were classified into three groups each had 30 participants first group diabetic with atherosclerotic complications, second was diabetics without any complications while third group was non diabetics as control all of them were subjected to assessment of blood sugar and lipid profile and Apo E alle...
Chang, Wei-Chiao; Fang, Yong-Yuan; Chang, Hsueh-Wei; Chuang, Li-Yeh; Lin, Yu-Da; Hou, Ming-Feng; Yang, Cheng-Hong
Background ORAI1 channels play an important role for breast cancer progression and metastasis. Previous studies indicated the strong correlation between breast cancer and individual single nucleotide polymorphisms (SNPs) of ORAI1 gene. However, the possible SNP-SNP interaction of ORAI1 gene was not investigated. Results To develop the complex analyses of SNP-SNP interaction, we propose a genetic algorithm (GA) to detect the model of breast cancer association between five SNPs (rs12320939, rs1...
Jovel Irina T; Mejía Rosa E; Banegas Engels; Piedade Rita; Alger Jackeline; Fontecha Gustavo; Ferreira Pedro E; Veiga Maria I; Enamorado Irma G; Bjorkman Anders; Ursing Johan
Abstract Background In Honduras, chloroquine and primaquine are recommended and still appear to be effective for treatment of Plasmodium falciparum and Plasmodium vivax malaria. The aim of this study was to determine the proportion of resistance associated genetic polymorphisms in P. falciparum and P. vivax collected in Honduras. Methods Blood samples were collected from patients seeking medical attention at the Hospital Escuela in Tegucigalpa from 2004 to 2006 as well as three regional hospi...
Konno, Akitsugu; Inoue-Murayama, Miho; Hasegawa, Toshikazu
We tested for an association between variable number of tandem repeats in the canine androgen receptor (AR) gene and personality differences in Japanese Akita Inu dogs. The polymorphic trinucleotide (CAG) repeat region coding for glutamine in exon 1 of the AR gene was genotyped using genomic DNA obtained from 171 dogs. Three alleles (23, 24 and 26 repeats) were detected, and the allele frequency differed with the coat colour. We assessed the personality profiles of 100 fawn-coloured dogs (54 ...
Tsai, Alex; Huang, Chu-Chung; Yang, Albert C.; Liu, Mu-En; Tu, Pei-Chi; Hong, Chen-Jee; Liou, Ying-Jay; Chen, Jin-Fan; Lin, Ching-Po; Tsai, Shih-Jen
Aims β-Site amyloid precursor protein (APP)-cleaving enzyme 1 (BACE1) is a biological and positional candidate gene for Alzheimer's disease (AD). Previous studies found that BACE1-null mice had impaired performance on cognition and neurodegeneration during the aging process. Additionally, a synonymous polymorphism of BACE1 (rs638405) in exon 5 has been reported to be associated with risk for AD. We hypothesized that this BACE1 gene variant might influence regional brain volumes and cognitive ...
Vogel, Ulla Birgitte; Andersen, Vibeke; Christensen, Jane;
Objective: Intake of red and processed meat confers risk of colorectal cancer (CRC). We wanted to test whether heme in meat promotes carcinogenesis. Methods: Heme oxygenase-1 (HO-1, HMOX1) A-413T (rs2071746) was assessed in a nested case–cohort study of 383 CRC cases and 763 randomly selected...... for interaction=0.55). Conclusion: The studied HO-1 polymorphism was not associated with risk of CRC suggesting that heme from meat is not important in CRC development....
Németh, Nóra; Kovács-Nagy, Réka; Székely, Anna; Sasvári-Székely, Mária; Rónai, Zsolt
Impulsivity is a personality trait of high impact and is connected with several types of maladaptive behavior and psychiatric diseases, such as attention deficit hyperactivity disorder, alcohol and drug abuse, as well as pathological gambling and mood disorders. Polymorphic variants of the SNAP-25 gene emerged as putative genetic components of impulsivity, as SNAP-25 protein plays an important role in the central nervous system, and its SNPs are associated with several psychiatric disorders. ...
Butila Anamaria Todoran
Full Text Available Background: P-glycoprotein (P-gp, a drug efflux transporter, encoded by the gene MDR1 ABCB1 multidrug resistant, reduces the penetration through the brain by the AEDs. Overexpression of Pgp in blood-brain barrier in epileptic patients play an important rol in pharmacoresistance. The aim of this study was to evaluate a possible association between C1236T and G2677T ABCB1 gene polymorphisms and drug-resistant epilepsy in Romanian children.
Nelson, Elliot C.; Lynskey, Michael T.; Heath, Andrew C; Wray, Naomi; Agrawal, Arpana; Shand, Fiona L.; Henders, Anjali K; Wallace, Leanne; Todorov, Alexandre A; Schrage, Andrew J.; Madden, Pamela A. F.; Degenhardt, Louisa; Martin, Nicholas G.; Montgomery, Grant W
Genes encoding the opioid receptors (OPRM1, OPRD1, and OPRK1) are obvious candidates for involvement in risk for heroin dependence. Prior association studies commonly had samples of modest size, included limited single nucleotide polymorphism (SNP) coverage of these genes, and yielded inconsistent results. Participants for the current investigation included 1459 heroin dependent cases ascertained from maintenance clinics in New South Wales, Australia, 1495 unrelated individu...
Kis, Anna; Bence, Melinda; Lakatos, Gabriella; Pergel, Enikő; Turcsán, Borbála; Pluijmakers, Jolanda; Vas, Judit; Elek, Zsuzsanna; Brúder, Ildikó; Földi, Levente; Sasvári-Székely, Mária; Miklósi, Ádám; Rónai, Zsolt; Kubinyi, Enikő
The oxytocin system has a crucial role in human sociality; several results prove that polymorphisms of the oxytocin receptor gene are related to complex social behaviors in humans. Dogs' parallel evolution with humans and their adaptation to the human environment has made them a useful species to model human social interactions. Previous research indicates that dogs are eligible models for behavioral genetic research, as well. Based on these previous findings, our research investigated associ...
Shen, Wei; Zhang, Bin; Liu, Shuyun; Wu, Hongling; Gu, Xue; Qin, Lingzhi; Tian, Ping; Zeng, Yun; Ye, Linxiang; Ni, Zemin; Wang, Qi
Background Pregnancy is an important stimulus of bone lead release. Elevated blood lead levels (BLLs) may cause adverse pregnancy outcomes for mothers and harmful lead effects on fetuses. However, the reports about maternal BLL changes during pregnancy are conflicting to some extent. This article is to explore the variations in BLLs among pregnant women. The relationships of BLLs with methylenetetrahydrofolate reductase (MTHFR) gene C677T, A1298C, and G1793A polymorphisms, which are associate...
Childs, Emma; Hohoff, Christa; Deckert, Jürgen; Xu, Ke; Badner, Judith,; de Wit, Harriet
Caffeine produces mild psychostimulant and sometimes anxiogenic effects by antagonizing adenosine at A1 and A2A receptors, and perhaps through interactions with other transmitter systems. Adenosine receptors are colocalized and functionally interact with dopamine receptors in the brain. Thus, functional polymorphisms in the genes for either adenosine or dopamine receptors may affect responses to caffeine. In this study, we examined associations between self-reported anxiogenic effects of caff...
Valenti, L; Conte, D; A. Piperno; P. Dongiovanni; Fracanzani, A.; Fraquelli, M; Vergani, A.; Gianni, C; Carmagnola, L; Fargion, S
The A16V mitochondrial targeting sequence polymorphism influences the antioxidant activity of MnSOD, an enzyme involved in neutralising iron induced oxidative stress. Patients with hereditary haemochromatosis develop parenchymal iron overload, which may lead to cirrhosis, diabetes, hypogonadism, and heart disease. The objective of this study was to determine in patients with haemochromatosis whether the presence of the Val MnSOD allele, associated with reduced enzymatic activity, affects tiss...
Camillo La Mesa; Patrizia Andreozzi; Marco Calabresi
A wide number of supra-molecular association modes are observed in mixtures containing water and bile salts, BS, (with, eventually, other components). Molecular or micellar solutions transform into hydrated solids, fibres, lyotropic liquid crystals and/or gels by raising the concentration, the temperature, adding electrolytes, surfactants, lipids and proteins. Amorphous or ordered phases may be formed accordingly. The forces responsible for this very rich polymorphism presumably arise from th...
Wang, Yadong; Yang, Haiyan; Gao, Huiyan; Wang, Haiyu
Recently, we have read with great interest the article entitled "The association between polymorphisms in the leptin receptor (LEPR) gene and risk of breast cancer: a systematic review and pooled analysis" published online by Wang et al. (Breast Cancer Res Treat 136:231-239, 2012). This article suggests that the A allele of LEPR gene rs1137101 variant was low-penetrant risk factor for developing breast cancer. The result is encouraging. Nevertheless, several key issues are worth noticing. PMID:25863476