title: Congenital heart defects, maternal homocysteine, smoking, and the 677 C>T polymorphism in the methylenetetrahydrofolate reductase gene: evaluating gene-environment interactions.
abstract: OBJECTIVE
  This study was undertaken to investigate the association between congenital heart defects (CHD), and maternal homocysteine, smoking, and the MTHFR 677 C>T polymorphism.
  
  
  METHODS
  Plasma homocysteine concentrations, smoking status, and MTFHR 677 genotypes were determined in 275 white women who had pregnancies affected by CHDs and 118 white women who had a normal pregnancy.
  
  
  RESULTS
  Homocysteine concentrations were significantly higher among women who had affected pregnancies (P < .0001). The highest estimated risk for having a CHD-affected pregnancy was among women who were smokers, were in the highest quartile for homocysteine, and had the MTHFR 677 CC genotype (odds ratio [OR] 11.8; 95% CI 2.6-53.3).
  
  
  CONCLUSIONS
  Many CHDs are due to a complex interaction between lifestyle factors and genetic susceptibilities. Our results suggest that the combined effect of elevations in maternal homocysteine, smoking, and the MTHFR 677 C>T polymorphism increase the risk of having a CHD-affected pregnancy.
authors.affiliation: Department of Pediatrics, Arkansas Children's Hospital Research Institute, University of Arkansas for Medical Sciences, College of Medicine, Little Rock, AR, USA.
authors.forename: Charlotte A
authors.initials: CA
authors.lastname: Hobbs
authors.forename: S Jill
authors.initials: SJ
authors.lastname: James
authors.forename: Stefanie
authors.initials: S
authors.lastname: Jernigan
authors.forename: Stepan
authors.initials: S
authors.lastname: Melnyk
authors.forename: Yunxia
authors.initials: Y
authors.lastname: Lu
authors.forename: Sadia
authors.initials: S
authors.lastname: Malik
authors.forename: Mario A
authors.initials: MA
authors.lastname: Cleves
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D003596:Cytosine; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006330:Heart Defects, Congenital / Q000209:etiology* / Q000235:genetics; D006710:Homocysteine / Q000097:blood*; D006801:Humans; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics*; D011110:Polymorphism, Genetic; D011247:Pregnancy / Q000097:blood* / Q000235:genetics*; D012907:Smoking / Q000009:adverse effects*; D013941:Thymine
chemical_list: D006710:Homocysteine; D003596:Cytosine; D042965:Methylenetetrahydrofolate Reductase (NADPH2); D013941:Thymine