Association of MTR A2756G and MTRR A66G Polymorphisms With Male Infertility: An Updated Meta-Analysis

Area of Science:

• Genetics and Reproductive Biology
• Molecular Epidemiology
• Nutrigenomics

Background:

• Male infertility affects a significant portion of reproductive-aged men, with genetic factors playing a crucial role.
• Folate metabolism genes, including MTR and MTRR, are implicated in various physiological processes, potentially influencing male reproductive health.
• Polymorphisms in folate pathway genes may alter enzyme function, impacting DNA synthesis, repair, and methylation, which are vital for spermatogenesis.

Approach:

• A comprehensive meta-analysis was conducted, systematically searching major scientific databases (Google Scholar, PubMed, Science Direct) for relevant case-control studies.
• Data from 19 eligible studies, encompassing 3621 cases and 3327 controls, were extracted and statistically analyzed using Review Manager 5.4.
• Pooled odds ratios (OR) with 95% confidence intervals (CI) were calculated for MTR A2756G and MTRR A66G polymorphisms in relation to male infertility risk.

Key Points:

• The MTR A2756G polymorphism demonstrated a significant association with male infertility across multiple genetic models (allele, additive, recessive).
• Specifically, the allele model (G vs. A) showed an OR of 1.21 [1.03-1.42], the additive model (GG vs. AA) an OR of 2.31 [1.38-3.96], and the recessive model (GG vs. AG+AA) an OR of 2.10 [1.55-2.86].
• No significant association was found between the MTRR A66G polymorphism and the risk of male infertility.

Conclusions:

• The MTR A2756G polymorphism emerges as a potential genetic risk factor contributing to male infertility.
• The MTRR A66G polymorphism does not appear to be significantly associated with male infertility based on current evidence.
• Larger sample sizes in future studies are warranted to further validate and strengthen the observed associations between MTR A2756G and male infertility.