5,10-Methylenetetrahydrofolate reductase single nucleotide polymorphisms and gene-environment interaction analysis in non-syndromic cleft lip/palate

Non-syndromic cleft lip/palate (NSCL/P) is a common congenital defect in Mexico. Periconceptional intake of folic acid (FA) may reduce the risk of this malformation. Although the 5,10-methylenetetrahydrofolate reductase (MTHFR) enzyme participates in folate metabolism, several studies failed to find any association between NSCL/P and the MTHFR C677T and A1298C polymorphisms. However, interactions among NSCL/P, MTHFR gene polymorphisms, and FA intake have not been explored in Mexican populations. This case-control study included 132 patients with NSCL/P and 370 controls from Mexico City. Maternal FA consumption during pregnancy was examined, as were the MTHFR C677T and A1298C polymorphisms and gene-FA interactions. Maternal FA intake during the periconceptional period was lower in cases (1.5%) than in controls (13%), with the risk of delivering a child with NSCL/P lower in mothers who consumed FA (OR=0.29, 95% CI: 0.19-0.44). In addition, the risk of NSCL/P was lower in children with the TT than the CC genotype of MTHFR C677T (OR=0.39, 95% CI: 0.23-0.68), after Bonferroni correction and exclusion of stratification. No evidence of gene-FA interaction was found. These results indicate that maternal FA intake and the TT genotype of the MTHFR C677T polymorphism in children independently reduced the risk of NSCL/P in our population.