A meta-analysis and meta-regression of association between MTHFR A1298C polymorphism and nonsyndromic cleft lip/palate risk: An evaluation based on five genetic models.

OBJECTIVE: The present meta-analysis is intended to assess the association between NSCL/P risk and methylenetetrahydrofolate reductase (MTHFR) A1298C polymorphism in case-control studies. MATERIALS AND METHODS: The Web of Science, PubMed/Medline, Scopus, and Cochrane Library databases were searched for related articles published by April 2019. Review Manager 5.3 was applied to measure the odds ratios (ORs) with 95% confidence interval (CI) in the analyses assessing the strength of the association between A1298C polymorphism and NSCL/P risk. Results Sixteen studies were involved and analysed in this meta-analysis. Altogether, the reviewed articles included 2677 NSCL/P patients and 3669 controls. The pooled ORs of the allele, homozygote, heterozygote, dominant, and recessive models were 1.11 (95% CI: 0.94, 1.30; P=0.21), 1.14 (95% CI: 0.94, 1.37; P=0.18), 0.98 (95% CI: 0.80, 1.20; P=0.87), 1.03 (95% CI: 0.86, 1.22; P=0.79), and 1.18 (95% CI: 0.99, 1.41; P=0.07), respectively. The analysis did not identify any significant association between the polymorphism and the risk of NSCL/P in any ethnicity or source of controls. CONCLUSIONS: This meta-analysis revealed that A1298C polymorphism is not associated with NSCL/P susceptibility, and the subgroup analyses based on ethnicity and the source of cases further confirmed this result.