title: MTHFR C677T, A1298C and MS A2756G Gene Polymorphisms and Male Infertility Risk in a Chinese Population: A Meta-Analysis.
abstract: BACKGROUND
  Methylenetetrahydrofolate reductase gene (MTHFR C677T and A1298C) and methionine synthase gene (MS A2756G) polymorphisms have shown an association with male infertility risk in several ethnic populations. Although several studies have evaluated these associations in Chinese populations, their small sample sizes and inconsistent outcomes have prevented strong conclusions. Therefore, the present meta-analysis was performed with published studies to evaluate the associations of the three single nucleotide polymorphisms (SNPs) and male infertility in a Chinese population.
  
  
  METHODS
  We conducted a search of PubMed, Embase, Web of Science, Chinese National Knowledge Infrastructure (CNKI), China biology medical literature (CBM), VIP, and Chinese literature (Wan Fang) databases up to May 31, 2016. Odds ratios (ORs) and 95% confidence intervals (95%CIs) were used to assess the strength of associations with a random-effect model or a fixed-effect model based on the heterogeneity analysis results. Sensitivity analysis was used to confirm the reliability and stability of the meta-analysis.
  
  
  RESULTS
  A total of nine studies, including 1,713 cases and 1,104 controls, were included in the meta-analysis. The pooled results indicated that the MTHFR C667T polymorphism was significantly associated with increased risk of male infertility in the Chinese population in the allele model (T vs. C: OR = 1.47, 95%CI = 1.32-1.63), the dominant model (TT + CT vs. CC: OR = 1.51, 95%CI = 1.30-1.77), the additive model (TT vs. CC: OR = 2.08, 95%CI = 1.68-2.58) and the recessive model (TT vs. CT+CC: OR = 1.58, 95%CI = 1.31-1.90), whereas the MTHFR A1298C and MS A2756G polymorphisms were not risk factors. There was no significant heterogeneity in any genotype contrasts among the studies. The sensitivity analysis indicated that the results of this meta-analysis were relatively stable.
  
  
  CONCLUSIONS
  This study suggests that the MTHFR C667T polymorphism may contribute to the genetic susceptibility to male infertility in the Chinese population, whereas MTHFR A1298C and MS A2756G polymorphisms may be unrelated to male infertility. Studies with larger sample sizes and representative population-based cases and well-matched controls are needed to validate our results.
authors.affiliation: Department of Urology, Institute of Urology, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
authors.forename: Zhengju
authors.initials: Z
authors.lastname: Ren
authors.affiliation: Department of Evidence-Based Medicine and Clinical Epidemiology, West China Hospital, Sichuan University, Chengdu, China.
authors.forename: Pengwei
authors.initials: P
authors.lastname: Ren
authors.affiliation: Department of Urology, Institute of Urology, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Yang
authors.affiliation: Department of Urology, Institute of Urology, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
authors.forename: Kun
authors.initials: K
authors.lastname: Fang
authors.affiliation: Department of Urology, Institute of Urology, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
authors.forename: Shangqing
authors.initials: S
authors.lastname: Ren
authors.affiliation: Department of Urology, Institute of Urology, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Liao
authors.affiliation: Department of Urology, Institute of Urology, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
authors.forename: Shengzhuo
authors.initials: S
authors.lastname: Liu
authors.affiliation: Department of Urology, Institute of Urology, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
authors.forename: Liangren
authors.initials: L
authors.lastname: Liu
authors.affiliation: Department of Urology, Institute of Urology, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
authors.forename: Zhufeng
authors.initials: Z
authors.lastname: Peng
authors.affiliation: Department of Urology, Institute of Urology, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Dong
mesh_terms: D013766:5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase / Q000235:genetics*; D000483:Alleles; D002681:China; D016208:Databases, Factual; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D007248:Infertility, Male / Q000235:genetics* / Q000473:pathology; D008297:Male; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics*; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors
chemical_list: D042965:Methylenetetrahydrofolate Reductase (NADPH2); D013766:5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase