title: 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.
authors.affiliation: a Department of Molecular and Cell Biology, Faculty of Basic Sciences , University of Mazandaran , Babolsar , Iran.
authors.forename: Mohammad
authors.initials: M
authors.lastname: Karimian
authors.affiliation: a Department of Molecular and Cell Biology, Faculty of Basic Sciences , University of Mazandaran , Babolsar , Iran.|b Nano and Biotechnology Research Group, Faculty of Basic Sciences , University of Mazandaran , Babolsar , Iran.
authors.forename: Abasalt
authors.initials: A
authors.lastname: Hosseinzadeh Colagar
mesh_terms: D000483:Alleles; D016022:Case-Control Studies; D003198:Computer Simulation; D005787:Gene Frequency; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D007248:Infertility, Male / Q000235:genetics*; D008297:Male; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics*; D009154:Mutation; D020641:Polymorphism, Single Nucleotide
chemical_list: C573423:MTHFR protein, human; D042965:Methylenetetrahydrofolate Reductase (NADPH2)
keywords: G1793A transition; MTHFR gene; Male infertility; in silico analysis; meta-analysis