Association of the folate metabolizing pathway polymorphisms with male infertility susceptibility

Background: Infertility is a global health dilemma and a multifactorial disorder affecting approximately 10-15% of all couples. It has been shown that polymorphic variants of the genes encoding key enzymes of folate and methionine metabolism may influence DNA methylation. Methylene tetra hydrofolate reductase (MTHFR), methionine synthase (MTR) and methionine synthase reductase (MTRR) are three key enzymes of the homocysteine and folate metabolic pathways.Objective: Polymorphisms of the folate metabolizing pathway were associated with male infertility susceptibility.Materials and Methods: The data were extracted from published articles about the polymorphisms of MTHFR pathways and the infertility from 2000 to 2018. The polymorphisms of MTHFR rs1801133 C> T, MTR rs1805087 A> G, MTHFR rs1801131 A> C and MTRR rs1801394 were selected.Results: The MTHFR C677T mutation was reported a risk factor for male infertility in both azoospermia and oligoasthenoteratozoospermia patients, especially in Asian population. The MTHFR TC haplotype were determined as high risk in men infertility while men carring CC haplotype had lowest risk. On the other hand, the MTHFR A1298C mutation was not associated to male infertility. MTR A2756G and MTRR A66G were potential candidates in the pathogenesis of male infertility, but more case-control studies were required to avoid false-positive outcomes.Conclusion: In conclusion, the findings indicated that the genetic mutations in the folate-related enzyme genes played a significant role in male infertility.

Keywords:

Infertility , Folate Metabolizing Pathway , MTHFR rs1801131 A> C and MTHFR rs1801133 C> T , MTR rs1805087 A> G , MTRR rs1801394