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

• Published in: European journal of oral sciences Vol. 122; no. 2; pp. 109 - 113
• Main Authors: Estandia-Ortega, Bernardette, Velázquez-Aragón, José A., Alcántara-Ortigoza, Miguel A., Reyna-Fabian, Miriam E., Villagómez-Martínez, Sandra, González-del Angel, Ariadna
• Format: Journal Article
• Language: English
• Published: England Blackwell Publishing Ltd 01.04.2014
• Subjects: Adenine; Adolescent; Case-Control Studies; Child; Child, Preschool; Cleft Lip - genetics; cleft lip/palate; Cleft Palate - genetics; Cytosine; Dentistry; Female; folic acid; Folic Acid - therapeutic use; Gene Frequency - genetics; Gene-Environment Interaction; genetic association study; Genetic Variation - genetics; Genotype; Humans; Infant; Infant, Newborn; Male; Methylenetetrahydrofolate Reductase (NADPH2) - genetics; methylenetetrahydrofolate reductase gene; Mexico; Polymorphism, Genetic - genetics; Polymorphism, Single Nucleotide - genetics; Preconception Care; Pregnancy; Prenatal Care; Risk Factors; single nucleotide polymorphism; Thymine; Vitamin B Complex - therapeutic use; Mexico; methylenetetrahydrofolate reductase gene; cleft lip/palate; folic acid; single nucleotide polymorphism; genetic association study
• ISSN: 0909-8836; 1600-0722
• DOI: 10.1111/eos.12114

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.