Congenital heart defects, maternal homocysteine, smoking, and the 677 C>T polymorphism in the methylenetetrahydrofolate reductase gene: evaluating gene-environment interactions.
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.
Hobbs
Charlotte A
CA
Department of Pediatrics, Arkansas Children's Hospital Research Institute, University of Arkansas for Medical Sciences, College of Medicine, Little Rock, AR, USA.
James
S Jill
SJ
Jernigan
Stefanie
S
Melnyk
Stepan
S
Lu
Yunxia
Y
Malik
Sadia
S
Cleves
Mario A
MA
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
D006710:Homocysteine; D003596:Cytosine; D042965:Methylenetetrahydrofolate Reductase (NADPH2); D013941:Thymine