Meta-analysis supports association of a functional SNP (rs1801133) in the MTHFR gene with Parkinson's disease

The MTHFR is a candidate risk gene for Parkinson's disease (PD), and a functional SNP (rs1801133) in the coding region of this gene has been investigated for the associations with the illness extensively among worldwide populations, but overall the results were inconsistent. Here, to assess the relationship between rs1801133 and risk of PD in general populations, we conducted a systematic meta-analysis by combining all available case–control samples in European and Asian populations, with a total of 1820 PD cases and 7530 healthy controls, and the pooled odds ratios (ORs) and 95% confidence intervals (95% CIs) for rs1801133 and PD were calculated using the Mantel–Haenszel method with a fixed-effect model. Overall, rs1801133 was significantly associated with the risk of PD (allelic model, pooled OR = 1.212 for T allele, 95% CI = 1.097–1.340, p-value = 0.0002). When stratifying for ethnicity, significant association was also observed in European (allelic model, pooled OR = 1.187 for T allele, 95% CI = 1.058–1.332, p-value = 0.004) and Asian samples (allelic model, pooled OR = 1.293 for T allele, 95% CI = 1.058–1.580, p-value = 0.012) respectively. In addition, rs1801133 was also significantly associated with MTHFR mRNA expression in both CEU (European, p-value = 0.0149) and CHB (Chinese, p-value = 0.0178) HapMap populations. Collectively, our meta-analysis suggests that rs1801133 is significantly associated with susceptibility to PD in European and Asian populations, and MTHFR is likely an authentic risk gene for PD.     

Methylenetetrahydrofolate reductase C677T and methionine synthase A2756G polymorphisms influence on leukocyte genomic DNA methylation level

Methionine synthase (MTR) and methylenetetrahydrofolate reductase (MTHFR) enzymes are involved in the metabolism of methyl groups, and thus have an important role in the maintenance of proper DNA methylation level. In our study we aimed to evaluate the effect of the polymorphism A2756G (rs1805087) in the MTR gene on the level of human leukocyte genomic DNA methylation. Since the well-studied polymorphism C677T (rs1801133) in the MTHFR gene has already been shown to affect DNA methylation, we aimed to analyze the effect of MTR A2756G independently of the MTHFR C677T polymorphism. For this purpose, we collected the groups of 80 subjects with the MTR 2756AA genotype and 80 subjects with the MTR 2756GG genotype, having equal numbers of individuals with the MTHFR 677CC and the MTHFR 677TT genotypes, and determined the level of DNA methylation in each group. Individuals homozygous for the mutant MTR 2756G allele showed higher DNA methylation level than those harboring the MTR 2756AA genotype (5.061 ± 1.761% vs. 4.501 ± 1.621%, P = 0.0391). Individuals with wild-type MTHFR 677СC genotype displayed higher DNA methylation level than the subjects with mutant MTHFR 677TT genotype (5.103 ± 1.767% vs. 4.323 ± 1.525%, P = 0.0034). Our data provide evidence that the MTR A2756G polymorphism increases the level of DNA methylation and confirm the previous reports that the MTHFR C677T polymorphism is associated with DNA hypomethylation.     

Methylenetetrahydrofolate reductase (MTHFR) gene polymorphisms and susceptibility to ischemic stroke: A meta-analysis

Associations between 5,10-methylenetetrahydrofolate reductase (MTHFR) gene C677T polymorphism and ischemic stroke have been reported (Ariyaratnam et al., 2007; Banerjee et al., 2007; Casas et al., 2004), but the results of these studies are inconsistent. To investigate the possible associations between the MTHFR gene polymorphism and ischemic stroke, we performed a meta-analysis. Nineteen case–control studies associated with MTHFR gene C667T involving 2223 cases and 2936 controls were included. Heterogeneity among studies was evaluated with I² and Egger's test and an inverted funnel plot was used to assess publication bias. Odds ratio (OR) was observed to identify the associations. Statistically significant association with ischemic stroke was identified for allele T polymorphism of MTHFR [fixed-effects OR = 1.28, 95% confidence interval (95% CI): 1.17–1.40, P < 0.00001] and marginally significant association was detected with genotype CT of MTHFR (fixed-effects OR = 1.13, 95% CI: 1.01–127, P = 0.04) and genotype TT of MTHFR (fixed-effects OR = 1.43, 95% CI: 1.20–1.70, P < 0.001). The results suggested that the MTHFR C667T genetic polymorphism was significantly associated with increased risk of ischemic stroke.     

Methylenetetrahydrofolate reductase C677T mutation in patients with alopecia areata in Turkish population

Objective

Methylene-tetrahydrofolate reductase (MTHFR) is a key enzyme regulating folate metabolism and it is thought to influence DNA methylation and nucleic acid synthesis. Mutations in the MTHFR gene have been associated with several autoimmune disorders in previous studies. Alopecia areata (AA) is considered to be a tissue-specific autoimmune disease as the hair follicle has been targeted and antibodies to their own hair follicle structures have been developed. Since there is a common shared pathway between AA and other autoimmune disorders, we aimed to investigate a possible association between the MTHFR gene C677T mutation and AA susceptibility in the Turkish population.

Methods

The study included 136 patients affected by AA and 130 healthy controls. Genomic DNA was isolated and genotyped using a polymerase chain reaction (PCR)-based restriction fragment length polymorphism (RFLP) assay for the MTHFR gene C677T mutation.

Results

The distributions of genotype and allele frequencies of MTHFR gene C677T mutation were statistically different between AA patients and the control group (p = 0.036 and p = 0.011, respectively). High differences were also observed when the patients and controls were compared according to CC versus CT + TT (p = 0.012). CT + TT genotypes and T allele of MTHFR gene C677T mutation were found to be a susceptibility factor for AA in the Turkish population.

Conclusion

The results suggest that MTHFR gene C677T mutation may have an effect on the risk of alopecia areata in the Turkish population. This is the first study reporting the association between the MTHFR (C677T) genotype and AA.     

Epistasis effects of COMT and MTHFR on inter-individual differences in mental health: Under the inverted U-shaped prefrontal dopamine model

Higher cognitive performance, maintenance of mental health and psychological well-being require adequate prefrontal cortex (PFC) function. “Inverted U-shaped” dopamine model indicates optimal PFC dopamine level is important to attain its function while high or low levels have adverse effects. Catechol-O-methyltransferase (COMT) and methylenetetrahydrofolate reductase (MTHFR) may be involved in this complex non-linear PFC dopamine regulation. We addressed whether genetic variation reflecting COMT and MTHFR activities can explain the inter-individual mental health differences in healthy Japanese men (n = 188). The mental health was measured by Mental Health Inventory (MHI)-5 score. The rs4633–rs4818–rs4680 haplotypes were used to represent the multilevel COMT activities, while for MTHFR, the functional single polymorphism, rs1801133 (C677T), was used. We examined the effectiveness of haplotype-based association analysis of COMT on mental health together with studying its interaction with MTHFR-C677T. As a result, the relation between activity-ranked COMT genotype and MHI-5 score showed a tendency to fit into an “inverted U-shaped” quadratic curve (P = 0.054). This curvilinear correlation was significant in the subjects with MTHFR-CC (P < 0.001), but not with MTHFR T-allele carriers (P = 0.793). Our pilot study implies a potential influence of COMT and MTHFR genotypic combination on normal variation of mental health.     

Methylenetetrahydrofolate reductase C677T and A1298C polymorphisms and variations of homocysteine concentrations in patients with Behcet's disease

Background

Behcet's disease (BD) is a chronic, relapsing, multi-systemic inflammatory disorder of unknown causes. This disease is mainly characterized by mucocutaneous, ocular, vascular, and central nervous system manifestations. The aim of this study is to investigate the associations between C677T and A1298C polymorphisms in the methylenetetrahydrofolate reductase (MTHFR) gene and the plasma homocysteine (Hcy), folate, and B12 levels in a relatively large cohort of Tunisian patients with BD.

Methods

The study included 142 patients with BD and 172 healthy controls. The C677T and A1298C polymorphisms were genotyped using PCR-RFLP. Serum Hcy level was determined using a fluorescence polarization immunoassay. Serum folate and vitamin B12 levels were measured by electrochemiluminescence immunoassay.

Results

Genotype and allele frequencies of the two studied MTHFR polymorphisms did not show any significant differences among BD patients compared to controls. Patient carriers of the 677TT variant and the 677 T allele displayed significantly higher Hcy concentration. Moreover, no significant association was found between neither A1298C polymorphism nor the C allele and Hcy, folate, and B12 levels. In multivariate analyses, we reported that 677 T allele, male gender, and creatinine level were independent risk factors for hyperhomocysteinemia (HHC).

Conclusions

In the present study, we report the absence of any significant differences between genotype and allele frequencies for both studied polymorphisms among BD patients compared to healthy controls. Besides, we showed that the T allele of MTHFR C677T polymorphism influenced the Hcy level which is an independent risk factor for HHC in Tunisian BD patients.     

The Association of Methylenetetrahydrofolate Reductase Genotypes with the Risk of Childhood Leukemia in Taiwan

Background

Acute lymphoblastic leukemia (ALL) is the most prevalent type of pediatric cancer, the causes of which are likely to involve an interaction between genetic and environmental factors. To evaluate the effects of the genotypic polymorphisms in methylenetetrahydrofolate reductase (MTHFR) on childhood ALL risk in Taiwan, two well-known polymorphic genotypes of MTHFR, C677T (rs1801133) and A1298C (rs1801131), were analyzed to examine the extent of their associations with childhood ALL susceptibility and to discuss the MTHFR genotypic contribution to childhood ALL risk among different populations.

Methodology/Principal Findings

In total, 266 patients with childhood ALL and an equal number of non-cancer controls recruited were genotyped utilizing PCR-RFLP methodology. The MTHFR C677T genotype, but not the A1298C, was differently distributed between childhood ALL and control groups. The CT and TT of MTHFR C677T genotypes were significantly more frequently found in controls than in childhood ALL patients (odds ratios=0.60 and 0.48, 95% confidence intervals=0.42–0.87 and 0.24–0.97, respectively). As for gender, the boys carrying the MTHFR C677T CT or TT genotype conferred a lower odds ratio of 0.51 (95% confidence interval=0.32–0.81, P=0.0113) for childhood ALL. As for age, those equal to or greater than 3.5 years of age at onset of disease carrying the MTHFR C677T CT or TT genotype were of lower risk (odds ratio= 0.43 and 95% confidence interval=0.26–0.71, P=0.0016).

Conclusions

Our results indicated that the MTHFR C677T T allele was a protective biomarker for childhood ALL in Taiwan, and the association was more significant in male patients and in patients 3.5 years of age or older at onset of disease.     

Associations of variants in MTHFR and MTRR genes with male infertility in the Jordanian population

Folate pathway is expected to play an important role in spermatogenesis since it is involved in DNA synthesis, repair and methylation. The purpose of this study was to examine the association between male infertility and the MTHFR (C677T and A1298C) and MTRR (A66G) polymorphisms. A group of 300 males was recruited in this study from different Jordanian infertility clinics. Of these, 150 cases of infertile men that included oligozoospermia cases (n = 45), severe oligozoospermia (n = 71) and azoospermia (n = 34) were studied. The other 150 males were age matched fertile controls. Genotyping of MTHFR and MTRR polymorphisms was performed using PCR-RFLP technique. The results showed an association between MTHFR 677TT genotype and male infertility (P < 0.05). However, the distribution of MTHFR A1298C and MTRR A66G genotypes were not different between the fertile and infertile groups (P > 0.05). In addition, none of the examined polymorphisms was related to any of the semen parameters in the infertile group. In conclusion, this study showed that MTHFR C677T polymorphism is associated with male infertility in Jordanians.     

Methylenetetrahydrofolate reductase 677TT genotype might be associated with an increased lung cancer risk in Asians

Background

The association between methylenetetrahydrofolate reductase (MTHFR) 677C > T polymorphism and lung cancer risk has been studied in various populations with conflicting results. The aim of this study was to assess the association strength by a meta-analysis of published studies.

Methods

We searched PubMed and Chinese Biomedical (CBM) databases for relevant literatures published by July 18, 2012. Pooled odds ratio (OR) with 95% confidence interval (CI) was calculated to assess the strength of the association.

Results

A total of 20 studies comprising 11,653 cases and 12,032 controls were included in the final meta-analysis. Using the random effect model, we found that MTHFR 677TT variant genotype was associated with an increased lung cancer risk (OR = 1.26, 95% CI = 1.05–1.50, P = 0.011 for TT vs. CC; OR = 1.19, 95% CI = 1.03–1.37, P < 0.001 for TT vs. CC + CT; OR = 1.11, 95% CI = 1.02–1.22, P = 0.017 for T allele vs. C allele). In the further stratified analyses, the increased lung cancer risk was found in Asian subjects (OR = 1.31, 95% CI = 1.01–1.71, P = 0.045 for TT vs. CC; OR = 1.17, 95% CI = 1.00–1.38, P = 0.048 for TT vs. CC + CT). There were no evidences for obvious publication bias in the overall meta-analysis and Asian subjects.

Conclusions

MTHFR 677TT genotype might increase the susceptibility of lung cancer, especially in Asians.     

Methylenetetrahydrofolate reductase C677T variant in Moroccan patients with inflammatory bowel disease

Background

The association of genetic polymorphisms related to metabolism of homocysteine and folate with inflammatory bowel disease has been evidenced. Several studies have identified genetic variants of MTHFR as significant susceptibility loci for Crohn's disease (CD) and ulcerative colitis (UC). The C677T genetic polymorphism in the MTHFR gene is found to be associated with a thermolabile variant enzyme that shows a reduced activity. Therefore, we investigated whether the C677T variant confers genetic susceptibility to CD or UC and evaluated the genotype–phenotype associations in the Moroccan population.

Methods

The present study included 96 inflammatory bowel disease patients (68 patients with CD and 28 with UC) and 182 healthy controls. DNA samples were genotyped for the MTHFR (C677T) mutation by the PCR-RFLP method. Statistical analyzes were performed using MedCalc software, Chi square test and Fisher test.

Results

The respective odds ratio for CD, UC and control group were, 1.55 (CI 95%: 0.53–4.53, P = 0.52); 0.50 (CI 95%: 0.06–4.15, P = 0.52) and 0.50 (CI 95%: 0.06–4.15, P = 0.52). Thus, no statistically significant association with the disease was observed in frequency of the TT variant in comparison to healthy controls. Stratification of IBD patients on the basis of CD or UC showed that individuals carrying at least one T allele are not protected against Crohn's disease. Furthermore, clinical features of the disease did not show any significant association.

Conclusion

In conclusion, the present study indicates that the genetic risk for IBD is not modulated by MTHFR C677T polymorphism in Moroccan population.     

Prediction value of intercellular adhesion molecule-1 gene polymorphisms for epithelial ovarian cancer risk,clinical features,and prognosis

Intercellular adhesion molecule-1 (ICAM-1, encoded by ICAM-1) is implicated in tumorigenesis and tumor progression. ICAM-1 modulates the susceptibility to several types of cancer and the disease prognosis; however, its role in epithelial ovarian cancer (EOC) is unclear. Here, we evaluate single nucleotide polymorphisms (SNPs) in ICAM-1 as predictors of EOC risk and prognosis. Six ICAM-1 polymorphisms were genotyped in 408 patients with EOC and 520 controls using the MassARRAY system. The ICAM-1 mRNA levels in 89 EOC tissues and 35 normal ovarian tissues were examined using quantitative PCR. The ICAM-1 rs5498 G allele was associated with increased tumor grade (OR = 2.650) and EOC risk (OR = 1.405). This risk was more evident in females who had first-degree relatives (FDRs) with a tumor (OR = 3.475) or who experienced early menarche (OR = 2.774). The ICAM-1 expression in the cancerous tissue was elevated compared with that of normal ovarian tissues (p < 0.0001), and it was associated with an rs5498 genotype (p = 0.0002). ICAM-1 SNPs did not significantly predict the overall EOC survival (p > 0.05). However, the rs5498 G allele correlated with EOC survival time in patients whose FDRs suffered from a tumor (p = 0.001). ICAM-1 rs5498 likely confers a high risk for EOC in G allele carriers accompanied by up-regulation of ICAM-1 expression during carcinogenesis. The combination of ICAM-1 rs5498 and tumor history predicts the EOC prognosis.     

Association of MTHFR and PPARγ2 gene polymorphisms in relation to type 2 diabetes mellitus cases among north Indian population

Background

Type 2 diabetes mellitus is a multifactorial and polygenic disease, which is considered as a major life threatening problem all over the world. There has been a worldwide effort in the identification of susceptibility genes for type 2 diabetes mellitus and its complications. At present, adequate data is not available dealing with MTHFR (rs1801133) and PPARγ2 (rs1801282) gene polymorphisms and its association with type 2 diabetes mellitus cases among north Indian populations. Thus, we conceived the need for further studies to investigate MTHFR and PPARγ2 gene polymorphisms and their susceptibility to type 2 diabetes mellitus in north Indian population.

Materials and methods

In this study, a total 175 subjects including 87 type 2 diabetes mellitus cases and 88 controls were enrolled. MTHFR and PPARγ2 gene polymorphisms in the cases and controls were evaluated by polymerase chain reaction and restriction fragment length polymorphism (PCR–RFLP).

Results

The MTHFR gene CC, CT, TT genotype frequencies obtained were 40%, 43%, and 17% in type 2 diabetes mellitus cases and 56%, 29%, and 15% in healthy controls respectively. The OR for CC was 0.54 (95%CI 0.29–0.98, P = 0.041, χ2 = 4.18, power = 0.98), for CT 1.76 (95%CI 0.94–3.30, P = 0.07, χ2 = 3.2, power = 0.96), and for TT 1.2 (95%CI 0.53–2.70, P = 0.66, χ2 = 0.198, power = 0.76). The PPARγ2 gene GG CG, CC genotype frequencies obtained were 28%, 41%, and 31% in cases and 40%, 39%, and 21% in healthy controls respectively. OR for GG was 0.58 (95%CI 0.30–1.09, P = 0.08, χ2 = 2.9, power = 0.96), for CG 1.12 (95%CI 0.61–2.05, P = 0.71, χ2 = 0.137, power = 0.778), and for CC 1.63 (95%CI 0.82–3.23, P = 0.156, χ2 = 2.01, power = 0.92).

Conclusion

It might be recommended that MTHFR CC genotype seems to be a good marker for the early identification of population at risk of type 2 diabetes mellitus. While we have detected significant difference in allelic frequencies of PPARγ2 C (Proline) and G (Alanine), but at genotypic level significant difference was not detected in this case–control study. Further study with larger groups may be required to validate the study.     

Association between IL13 gene polymorphisms and susceptibility to cancer: A meta-analysis

Background/aims

Interleukin-13 (IL13) is an immunoregulatory cytokine which plays an important role in carcinogenesis through affecting tumor immunosurveillance. Many studies had reported the influence of IL13 rs1800925 and rs20541 polymorphisms on cancer risk, however, with inconclusive results. The aim of the present study was to conduct a meta-analysis to clarify the relationship.

Methods

Twenty studies including a total of 6713 cancer cases and 8693 controls for IL13 rs20541 polymorphism and 4081 cancer cases and 6202 controls for IL13 rs1800925 polymorphism were included in the meta-analysis. Data were extracted from these studies and odds ratios with corresponding 95% confidence intervals were computed to estimate the strength of the association.

Results

Overall, the IL13 rs20541 polymorphism were associated with significantly decreased cancer risk in all genetic models (AA vs. GG: OR = 0.82, 95%CI = 0.71–0.95; GA vs. GG: OR = 0.92, 95%CI = 0.85–0.99; GA/AA vs. GG: OR = 0.90, 95%CI = 0.85–0.97; AA vs. GG/GA: OR = 0.85, 95CI% = 0.74–0.98). In the stratified analyses, significant effects were found among European populations, studies with population-based controls and studies of glioma. No influence of the IL13 rs1800925 polymorphism on the overall cancer risk was observed. However, in the stratified analyses, we found the IL13 rs1800925 polymorphism was significantly associated with decreased risk for glioma (CT vs. TT: OR = 0.72, 95%CI = 0.55–0.93; CT/TT vs. TT: OR = 0.76, 95%CI = 0.62–0.89).

Conclusion

Our meta-analysis suggests that the IL13 rs20541 polymorphism contributes to susceptibility to cancer, especially for glioma; and the IL13 rs1800925 polymorphism may be associated with glioma risk.     

Association of TLR and TREM-1 gene polymorphisms with risk of coronary artery disease in a Russian population

Atherosclerosis, manifesting itself as acute coronary syndrome, stroke, and peripheral arterial diseases, is a chronic progressive inflammatory disease which is driven by responses of both innate and adaptive immunity. Toll-like receptors (TLRs) and Triggering Receptor Expressed on Myeloid Cells-1 (TREM-1) are important effectors of the innate immune system, and polymorphisms within genes encoding them may increase risk of occurrence of various pathologies including cardiovascular disorders. Thus, we carried out a genetic association study on the sample of 702 consecutive Caucasian (Russian) patients with coronary artery disease (CAD) and 300 age-, sex-, and ethnicity-matched healthy controls. We revealed that the C/C genotype of the TLR1 rs5743551 polymorphism was significantly associated with a reduced risk of CAD according to the recessive model (OR = 0.41, 95% CI = 0.20–0.84, P = 0.017, adjusted by age and gender). Concerning TREM-1 gene polymorphisms, we found that A/A genotype of the rs2234237 polymorphism, the G/G genotype of the rs6910730 polymorphism, the C/C genotype of the rs9471535 polymorphism, and the T/T genotype of the rs4711668 polymorphism were significantly associated with elevated CAD risk according to the recessive model (OR = 5.52, 95% CI = 1.17–25.98, P = 0.011; OR = 4.28, 95% CI = 1.09–16.81, P = 0.021; OR = 5.55, 95% CI = 1.18–26.09, P = 0.011, and OR = 1.66, 95% CI = 1.10–2.52, P = 0.014, respectively, adjusted by age and gender). Conversely, the G allele of the rs1817537 polymorphism, the T allele of the rs2234246 polymorphism, and the T allele of the rs3804277 polymorphism significantly correlated with similarly decreased risk of CAD according to the dominant model (OR = 0.57, 95% CI = 0.40–0.81, P = 0.0013; OR = 0.59, 95% CI = 0.42–0.84, P = 0.003, and OR = 0.58, 95% CI = 0.41–0.81, P = 0.0014, respectively, adjusted by age and gender). We conclude that certain TLR and TREM-1 gene polymorphisms may be associated with CAD in Russian population; however, their significance as predictive and pathogenic markers of CAD should be interpreted with caution in other populations.     

Association between MDR1 C3435T polymorphism and risk of breast cancer

The C3435T (rs1045642) polymorphism, located in multi-drug resistance gene 1 (MDR1), has demonstrated its role in decreasing the P-gp activity level which is related to the carcinogenesis. Many published studies have evaluated the association between the MDR1 C3435T polymorphism and breast cancer risk. However, the results remain conflicting rather than conclusive. To derive a more precise estimation of the association between MDR1 C3435T polymorphism and risk of breast cancer, we performed a meta-analysis comprised of 10 case–control studies, including 5282 breast cancer cases and 7703 controls. Odds ratios (ORs) and 95% confidence intervals (CIs) were used to evaluate the strength of the association. The overall results indicated that the variant genotypes were associated with a significantly increased risk of breast cancer (TT versus CC: OR = 1.45, 95% CI = 1.14–1.30, TT versus CT/CC: OR = 1.13, 95% CI = 1.04–1.23, TT/CT versus CC: OR = 1.22, 95% CI = 1.02–1.46). Our results suggest that the MDR1 C3435T polymorphism may contribute to individual susceptibility to breast cancer.     

The polymorphism − 1131T > C in apolipoprotein A5 gene is associated with dyslipidemia in Brazilian subjects

Background

Polymorphisms in apolipoprotein A5 gene (APOA5) have been associated with higher triglyceride levels in many populations. The aim of the study was to determine the allelic and genotypic distribution of the APOA5 − 1131T > C polymorphism and to identify the association of the genetic variant and the risk for dyslipidemia.

Methods

We genotyped 109 dyslipidemic subjects and 107 controls. The total cholesterol, triglycerides and HDL-c were determined enzymatically. Comparison of means among groups was calculated by ANOVA. Significant differences among groups were evaluated by Student–Newman–Keuls test.

Results

The minor allele C was more frequent in dyslipidemic subjects than controls (p = 0.019) and confers an increased individual risk for dyslipidemia (OR = 1.726, CI 95% = 1.095–2.721). The genotype analysis by gender showed that this allele was more frequent in dyslipidemic males (p = 0.037; OR = 2.050, CI 95% = 1.042–4.023). When participants were analyzed according to genotypes TT and TC/CC, C-carriers presented higher cholesterol and triglycerides levels than TT homozygous (p = 0.046 and 0.049, respectively).

Conclusions

The allele C confers higher total cholesterol and triglycerides levels in dyslipidemic adults. The APOA5 − 1131T > C polymorphism is associated with dyslipidemia in male subjects.     

Cloning and expression analysis of novel Aux/IAA family genes in Gossypium hirsutum

The associations between polymorphisms of prostate stem cell antigen (PSCA-rs2294008C > T and -rs2976392G > A) and gastric cancer (GC) risk for Eastern Asians have been commonly studied, but the results were conflicting. The aim of the present study was to further assess the associations by the method of meta-analysis. The databases of Medline, Embase and CNKI (up to May 25th, 2011) were retrieved to identify eligible case-control studies. Odds ratio (OR) and 95% confidence interval (95%CI) were used to present the strength of the associations. In total, eight case-control studies in seven articles with 16792 individuals (9738 cases of GC and 7054 controls) were included in this meta-analysis. Through quantitative analyses, we found that T allele of rs2294008C > T and A allele of rs2976392G > A were significantly associated with increased GC risk [rs2294008C > T: OR (95%CI) = 1.31 (1.22-1.42), P_z-test < 0.001, P_{heterogeneity} = 0.166 for TT vs. C carriers; rs2976392G > A: OR (95%CI) = 1.36(1.24-1.50), P_z-test = 0.015, P_{heterogeneity} = 0.111 for AA vs. G carriers]. The results of subgroup analyses (according to histopathology, countries and sources of controls) indicated that T allele of rs2294008C > T and A allele rs2976392G > A were associated with increased risk of both intestinal- and diffuse-type GC, and associated with increased risk of GC for Chinese, Japanese, Koreans, PCC and HCC/PHCC. Furthermore, T allele of rs2294008C > T was also associated with increased risk of cardia and non-cardia GC, and associated with increased risk of GC for males and females. Besides those, this meta-analysis also indicated that the interactions between T allele of rs2294008C > T and A allele of rs2976392G > A was associated with increased risk of GC (A-T vs. G-T: OR = 1.16, 95%CI = 1.06-1.27, P_z-test = 0.001, P_{heterogeneity} = 0.835). Although modest limitations and potential bias cannot be eliminated, this meta-analysis suggests that PSCA -rs2294008C > T and -rs2976392G > A are potential factors of GC development for Eastern Asians, and future work may incorporate these findings and evaluate these variants as potential markers for screening and early diagnosis of GC.     

Single nucleotide polymorphism of CD40 in the 5′-untranslated region is associated with ischemic stroke

Objectives

Ischemic stroke is influenced by both environmental and genetic factors. The CD40/CD40L system is related to proinflammatory and prothrombogenic responses, which are involved in the pathophysiology of ischemic stroke. The aim of this study was to evaluate association between the CD40 -1C/T single nucleotide polymorphism (SNP) and ischemic stroke in a Chinese population.

Methods

We conducted a case–control study including 286 ischemic stroke patients and 336 controls. CD40 -1C/T SNP was genotyped using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and DNA sequencing methods, and evaluated its relevance to ischemic stroke susceptibility.

Results

Significantly increased ischemic stroke risk was found to be associated with the T allele of CD40 -1C/T (OR = 1.273, 95% CI = 1.016–1.594). The frequencies of CT and TT/CT genotypes of CD40 -1C/T in ischemic stroke patients were significantly higher than those of controls, respectively (for CT: OR = 2.350, 95% CI = 1.601–3.449; for TT/CT: OR = 2.148, 95% CI = 1.479–3.119). And, similar results were obtained after adjusting non-matched variables. We found that the frequency of carried T genotypes (TT and TT/CT) was significantly increased in patients with history of stroke compared with patients without (for TT: OR = 6.538, 95%CI = 1.655–25.833; for TT/CT: OR = 3.469, 95%CI = 1.031–11.670), respectively.

Conclusions

The findings suggested that the CD40 -1C/T polymorphism might contribute to the susceptibility to ischemic stroke in the Chinese population, and might be associated with history of previous stroke.     

Association of TGF-β1 − 509 C/T, 29 C/T and 788 C/T gene polymorphisms with chronic periodontitis: A case–control study

The aim of this study was to investigate the possible association between TGF-β1 − 509 C/T (rs1800469), 29 C/T (Prol10Leu, rs1800470) and 788 C/T (Thr263Ile, rs1800472) gene polymorphisms and chronic periodontitis (CP) in a sample of Iranian population. This case–control study was conducted on 100 CP patients and 100 healthy unrelated, age-, sex-, and ethnicity-matched. Genotyping was performed by tetra amplification refractory mutation system-polymerase chain reaction (T-ARMS-PCR) technique. Our findings showed that there was a significant difference between the groups regarding TGF-β1 29 C/T (rs1800470) polymorphism (χ2 = 23.23, P < 0.0001). The CT and TT genotypes increased the risk of CP in comparison with the CC genotype (OR = 4.42, 95% CI = 2.16–9.06, P < 0.001 and OR = 5.84, 95% CI = 2.32–14.71, P < 0.001, respectively). The T allele increased the risk of CP (OR = 2.50, 95% CI = 1.66–3.74, P < 0.001) in comparison with C allele. No significant association was found among the groups regarding − 509 C/T and 788 C/T variants of TGF-β1 gene. This study shows that TGF-β1 29 C/T polymorphism, but not − 509 C/T and 788 C/T polymorphisms, may contribute to the development of CP in a sample of Iranian population. Further studies with larger sample sizes and different ethnicities are needed to validate our findings.     

Association between Methylenetetrahydrofolate Reductase C677T Polymorphism and Susceptibility to Cervical Cancer: A Meta-Analysis

Background

To assess the association between MTHFR polymorphism and cervical cancer risk, a meta-analysis was performed.

Methods

Based on comprehensive searches of the PubMed, Embase, and Web of Science databases, we identified outcome data from all articles estimating the association between MTHFR polymorphism and cervical cancer risk. The pooled odds ratio (OR) with 95% confidence intervals (CIs) were calculated.

Results

A total of 12 studies with 2,924 cases (331 cervical intraepithelial neoplasia (CIN) I, 742 CIN II/III, 1851 invasive cervical cancer) and 2,581 controls were identified. There was no significant association between MTHFR C677T polymorphism and CIN I risk (T vs. C, OR = 1.10, 95% CI = 0.92–1.31; TT vs. CC, OR = 1.14, 95% CI = 0.78–1.68; TT+CT vs. CC, OR = 1.22, 95% CI = 0.94–1.58; TT vs. CT+CC, OR = 0.99, 95% CI = 0.70–1.40). For the CIN II/III, lack of an association was also found (T vs. C, OR = 1.08, 95% CI = 0.95–1.23; TT vs. CC, OR = 1.15, 95% CI = 0.87–1.52; TT+CT vs. CC, OR = 1.13, 95% CI = 0.94–1.35; TT vs. CT+CC, OR = 1.07, 95% CI = 0.83–1.38). The T allele had significant association to susceptibility of invasive cervical cancer in recessive model (TT vs. CT+CC, OR = 1.23, 95% CI = 1.02–1.49). On subgroup analysis by ethnicity, similarly significant differences in T vs. C, TT vs. CC, and recessive model were found in Asians.

Conclusion

The present meta-analysis suggested that MTHFR C677T polymorphism were to substantially contribute to invasive cervical cancer in recessive model.