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

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.

Association of the MTHFR 677C>T and 1298A>C polymorphisms and male infertility risk: a meta-analysis

“…The N. Gupta and colleagues studied the Indian population [18], Wiener's worked on the men's idiopathic infertility in Russian population [19], Z. Ren and colleagues studied the Chinese population [20], and V. Rai and P. Kumar research [21] focused on the relationship between one type of MTHFR A1298C and male infertility.…”

The relevance of MTHFR C677T, A1298C, and MTRR A66G polymorphisms with response to male infertility in Asians

“…[10] Weiner's study with 275 men of idiopathic male infertility and 349 controls was limited to Russian population. [11] Ren's study including 1713 cases and 1104 controls was limited to Chinese population, [12] and Rai's research with 4392 breast infertile males and 3667 fertile males has not included the latest research data after March 2015. [13] Only Ren et al have evaluated the association between MTHFR A1298C and male infertility.…”

“…[13] Only Ren et al have evaluated the association between MTHFR A1298C and male infertility. [12] The system review with respect to MTRR A66G polymorphism specifically for Asian populations has not been reported till date. Therefore, it is necessary to collect more studies in a large sample size for further elucidating correlation between these polymorphisms and male infertility in Asians.…”

The association between MTHFR polymorphism and cervical cancer

“…MTHFR catalyzes the conversion of 5,10-methylenetetrahydrofolate acid into 5-methyltetrahydrofolate acid which is a major circulating form of folate acid. The single nucleotide polymorphisms (SNPs) in the MTHFR gene: C677T (rs1801133) and A1298C (rs1801131) had functional relevance to alter the enzyme activity 8 . Thus, MTHFR variation may be associated with variable folate acid levels in folate acid metabolic pathway.…”