Methylenetetrahydrofolate reductase C677T polymorphism and the risk of male infertility: a meta-analysis

Int J Androl. 2012 Feb;35(1):18-24. doi: 10.1111/j.1365-2605.2011.01147.x. Epub 2011 Apr 28.


Several molecular epidemiological studies have been conducted to examine the association between MTHFR C677T polymorphism and male infertility susceptibility, but the results remain inconsistent. To derive a more precise estimation of the relationship, a meta-analysis was performed. A total of 10 case-control studies, including 2275 cases and 1958 controls, were selected. Crude odds ratios (ORs) with 95% confidence intervals were used to assess the strength of association in the additive model, dominant model and recessive model. In the overall analysis, no significant association between the polymorphism and risk of male infertility was observed. Stratified analysis showed that significantly strong association between MTHFR C677T polymorphism and male infertility were present only in Asians (OR = 1.79 for TT vs. CC genotype; OR = 1.42 for CT/TT vs. CC genotype; OR = 1.50 for TT vs. CC/CT genotype; OR = 1.36 for T vs. C allele), but not in Caucasians. Additionally, MTHFR 677T was associated with a significant increase in the risk of azoospermia in all genetic models. No significantly increased risks of oligoasthenoteratozoospermia were found in any of the genetic models. In conclusion, this meta-analysis supports that MTHFR C677T polymorphism is capable of causing male infertility susceptibility in Asians, but not in Caucasians.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Case-Control Studies
  • Humans
  • Infertility, Male / genetics*
  • Male
  • Methylenetetrahydrofolate Reductase (NADPH2) / genetics*
  • Polymorphism, Genetic*


  • Methylenetetrahydrofolate Reductase (NADPH2)