Human MTHFR-G1793A transition may be a protective mutation against male infertility: a genetic association study and in silico analysis

Abstract

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, p = 0.0052) and A allele (OR: 0.4266, 95%CI: 0.2267–0.8030, p = 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 =0.1809, p = 0.1095; 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.

Keywords:

• Male infertility
• MTHFR gene
• G1793A transition
• in silico analysis
• meta-analysis

Acknowledgements

We thank Dr. Seyed Gholam Ali Jorsarayi, from Fatemeh Zahra Hospital (Babol, Iran), and our colleges in Molecular and Cell Biology Laboratory of University of Mazandaran for proofreading and editing the manuscript.

Disclosure statement

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of this article.