title: Gene-gene interactions in the folate metabolic pathway and the risk of conotruncal heart defects.
abstract: Conotruncal and related heart defects (CTRD) are common, complex malformations. Although there are few established risk factors, there is evidence that genetic variation in the folate metabolic pathway influences CTRD risk. This study was undertaken to assess the association between inherited (i.e., case) and maternal gene-gene interactions in this pathway and the risk of CTRD. Case-parent triads (n = 727), ascertained from the Children's Hospital of Philadelphia, were genotyped for ten functional variants of nine folate metabolic genes. Analyses of inherited genotypes were consistent with the previously reported association between MTHFR A1298C and CTRD (adjusted P = .02), but provided no evidence that CTRD was associated with inherited gene-gene interactions. Analyses of the maternal genotypes provided evidence of a MTHFR C677T/CBS 844ins68 interaction and CTRD risk (unadjusted P = .02). This association is consistent with the effects of this genotype combination on folate-homocysteine biochemistry but remains to be confirmed in independent study populations.
authors.affiliation: Human Genetics Center, Division of Epidemiology and Disease Control, The University of Texas School of Public Health, 1200 Herman Pressler Drive, Houston, TX 77030, USA.
authors.forename: Philip J
authors.initials: PJ
authors.lastname: Lupo
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Goldmuntz
authors.forename: Laura E
authors.initials: LE
authors.lastname: Mitchell
mesh_terms: D002648:Child; D005260:Female; D005492:Folic Acid / Q000378:metabolism*; D020022:Genetic Predisposition to Disease; D006330:Heart Defects, Congenital / Q000201:enzymology / Q000235:genetics* / Q000378:metabolism*; D006801:Humans; D016014:Linear Models; D008297:Male; D053858:Metabolic Networks and Pathways; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics / Q000378:metabolism; D020641:Polymorphism, Single Nucleotide
chemical_list: D005492:Folic Acid; D042965:Methylenetetrahydrofolate Reductase (NADPH2)