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Both genetic and environmental factors affect the risk of orofacial clefts. The present meta-analysis aimed to evaluate the association between  methylenetetrahydrofolate reductase (MTHFR)  C677T polymorphism and risk of nonsyndromic cleft lip/palate (NSCL/P) in cases-control studies. The PubMed/Medline, Scopus, Web of Science, and Cochrane Library databases were searched up to April 2019 with no restrictions. The odds ratios (ORs) and 95% confidence intervals (CIs) in all analyses were calculated by Review Manager 5.3 software. The funnel plot analysis was carried out by the Comprehensive Meta-Analysis version 2.0 software. Subgroup analysis, meta-regression, and sensitivity analysis were performed for the pooled analyses. Thirty-one studies reviewed in this meta-analysis included 4710 NSCL/P patients and 7271 controls. There was no significant association between  MTHFR  C677T polymorphism and NSCL/P susceptibility related to allelic model (OR = 1.04; P = 0.49), homozygote model (OR = 1.11; P = 0.35), heterozygote model (OR = 0.99; P = 0.91), dominant model (OR = 1.00; P = 0.96), or recessive model (OR = 1.08; P = 0.23). There was no significant association between  MTHFR  C677T polymorphism and NSCL/P susceptibility based on the ethnicity or the source of cases. There was a significant linear relationship between the year of publication and log ORs for the allele model. The results of the present meta-analysis failed to show an association between  MTHFR  C677T polymorphism and NSCL/P susceptibility. The subgroup analyses based on the ethnicity and the source of cases further confirmed this result.

Methylenetetrahydrofolate reductase C677T polymorphism is not associated with the risk of nonsyndromic cleft lip/palate: An updated meta-analysis