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 M exico. 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 C 677 T and A 1298 C polymorphisms. However, interactions among NSCL / P , MTHFR gene polymorphisms, and FA intake have not been explored in M exican populations. This case–control study included 132 patients with NSCL / P and 370 controls from M exico C ity. Maternal FA consumption during pregnancy was examined, as were the MTHFR C 677 T and A 1298 C 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 B onferroni 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 C 677 T polymorphism in children independently reduced the risk of NSCL / P in our population.