In this paper, we evaluate the association of the human methylenetetrahydrofolate reductase (MTHFR)-G1793A transition with male infertility using a case-control study, a meta-analysis and an in silico analysis. In the case-control study, 308 blood samples (169 infertile and 139 fertile men) were collected. MTHFR-G1793A genotyping was performed by PCR-RFLP. The study revealed a significant protective association between the GA genotype (OR: 0.3737, 95%CI: 0.1874–0.7452, p¼0.0052) and A allele (OR: 0.4266, 95%CI: 0.2267–0.8030, p ¼ 0.0083) with male infertility. Meta-analysis showed that the G1793A transition might be a protective mutation against male infertility in both A vs. G (OR: 0.608, 95%CI: 0.466–0.792, p<0.001), and GA vs. GG (OR: 0.534, 95%CI: 0.394–0.724, p<0.001) genetic models. In silico-analysis revealed that although G1793A could not make fundamental changes in the function and structure of MTHFR, it could modify the structure of the mRNA (Distance ¼0.1809, p¼0.1095; p<0.2 is significant). The results suggest that G1793A substitution might be a protective genetic factor against male infertility. However, further case-control studies are required to provide a more robust conclusion.
