MTHFR C677T, A1298C and MS A2756G Gene Polymorphisms and Male Infertility Risk in a Chinese Population: A Meta-Analysis.

Zhengju Ren,Liangren Liu,Shangqing Ren,Shengzhuo Liu,Kun Fang,Bo Yang,Jian Liao,Qiang Dong,Zhufeng Peng,Pengwei Ren,Hao Deng

doi:10.1371/journal.pone.0169789

Abstract

BackgroundMethylenetetrahydrofolate 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.MethodsWe 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.ResultsA 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.ConclusionThis 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.

Highlights

Infertility is defined as the failure of a couple to achieve pregnancy after one year of unprotected, regular sexual intercourse, which affects approximately 15% of all couples attempting to conceive a child[1, 2]
The pooled results indicated that the methylenetetrahydrofolate reductase (MTHFR) C667T polymorphism was significantly associated with increased risk of male infertility in the Chinese population in the allele model (T vs. C: Odds ratios (ORs) = 1.47, 95% confidence intervals (95%CIs) = 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 methionine synthase (MS) A2756G polymorphisms were not risk factors
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

Summary

Introduction

Infertility is defined as the failure of a couple to achieve pregnancy after one year of unprotected, regular sexual intercourse, which affects approximately 15% of all couples attempting to conceive a child[1, 2]. Several single-nucleotide polymorphisms (SNPs) of folate metabolism-related genes have been identified, including methylenetetrahydrofolate reductase (MTHFR; 607093) gene polymorphisms (MTHFR C677T, rs1801133 and MTHFR A1298C, rs1801131), a methionine synthase (MS; 156570) gene polymorphism (MS A2756G, rs1805087, known as MTR A2756G), and a methionine synthase reductase (MTRR; 602568) gene polymorphism (MTRR A66G, rs1801394). These SNPs can affect the activity, stability, and level of folate metabolism-related enzymes, which may affect folate metabolism and DNA synthesis[9]. 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

Results

Conclusion