Congenital heart defects, maternal homocysteine, smoking, and the 677 C>T polymorphism in the methylenetetrahydrofolate reductase gene: evaluating gene-environment interactions.

This study was undertaken to investigate the association between congenital heart defects (CHD), and maternal homocysteine, smoking, and the MTHFR 677 C>T polymorphism. 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. 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). 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.