Methionine synthase(MTR)hasacrucial rolein DNAsynthesis and methylationreactions. The aimof this study was to investigate the association of the MTR-A2756G polymorphism with idiopathic male infertility. Blood samples were collected from 217 idiopathic infertile- and 233 healthy-men, and MTRA2756G genotyping was performed by PCR-RFLP. Meta-analysis was conducted by pooling our data with the data obtained from 6 previous studies. Also, the effects of this substitution on protein structure were evaluated by bioinformatics tools. Our study revealed the association of AG-genotype, GG-genotype, and G-allele with male infertility. Meta-analysis showed a significant association between A2756G transition and male infertility. In addition, structural analysis of the transition effect on protein revealed a significant influence on MTR function (with score: 38; expected accuracy: 66%). These findings suggest that the A2756G substitution might be a genetic risk factor and a potential biomarker for idiopathic male infertility.
