Associations Between MTR A2756G, MTRR A66G, and TCN2 C776G Polymorphisms and Risk of Nonsyndromic Cleft Lip With or Without Cleft Palate: A Meta-Analysis

Objective: We conducted a meta-analysis to investigate the associations of methionine synthase (MTR) A2756G, methionine synthase reductase (MTRR) A66G, and transcobalamin 2 (TCN2) C776G gene polymorphisms with nonsyndromic cleft lip with or without cleft palate (NSCL/P). Materials and Methods: The PubMed, Web of Science, Embase, and Wiley Online Library databases and the China Biomedical Literature Service System (SinoMed) were searched for relevant articles to explore the associations between the MTR A2756G, MTRR A66G, and TCN2 C776G polymorphisms and the risk of NSCL/P. We performed overall comparisons and stratified analyses according to the ethnicity, type of NSCL/P, and Hardy-Weinberg equilibrium (HWE) of the control group. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were applied to estimate the associations of these gene polymorphisms with NSCL/P risk using fixed-effects or random-effects models incorporating five genetic models. Results: Ultimately, 12 articles were included in this study. The pooled results did not reveal a significant association of the MTR A2756G polymorphism with NSCL/P risk (G vs. A: OR=0.95, 95% CI=0.82-1.11, p=0.55). Similar results were observed for the MTRR A66G polymorphism (G vs. A: OR=0.99, 95% CI=0.82-1.18, p=0.72) and the TCN2 C776G polymorphism (G vs. C: OR=0.95, 95% CI=0.86-1.06, p=0.37). Conclusion: In summary, the MTR A2756G, MTRR A66G, and TCN2 C776G polymorphisms might not be associated with NSCL/P risk.