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.
Laboratorio de Biología Molecular, Departamento de Genética Humana, Instituto Nacional de Pediatría, Distrito Federal, Mexico.
Bernardette
B
Estandia-Ortega
José A
JA
Velázquez-Aragón
Miguel A
MA
Alcántara-Ortigoza
Miriam E
ME
Reyna-Fabian
Sandra
S
Villagómez-Martínez
Ariadna
A
González-Del Angel
D000225:Adenine; D000293:Adolescent; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D002971:Cleft Lip / Q000235:genetics*; D002972:Cleft Palate / Q000235:genetics*; D003596:Cytosine; D005260:Female; D005492:Folic Acid / Q000627:therapeutic use; D005787:Gene Frequency / Q000235:genetics; D059647:Gene-Environment Interaction; D014644:Genetic Variation / Q000235:genetics; D005838:Genotype; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics*; D008800:Mexico; D011110:Polymorphism, Genetic / Q000235:genetics; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D016742:Preconception Care; D011247:Pregnancy; D011295:Prenatal Care; D012307:Risk Factors; D013941:Thymine; D014803:Vitamin B Complex / Q000627:therapeutic use
D014803:Vitamin B Complex; D003596:Cytosine; D005492:Folic Acid; C573423:MTHFR protein, human; D042965:Methylenetetrahydrofolate Reductase (NADPH2); D000225:Adenine; D013941:Thymine
cleft lip/palate; folic acid; genetic association study; methylenetetrahydrofolate reductase gene; single nucleotide polymorphism