Maternal folate-related gene environment interactions and congenital heart defects.
OBJECTIVE
To investigate whether women with congenital heart defect (CHD)-affected pregnancies were more likely to have functional single-nucleotide polymorphisms in genes encoding enzymes in folate-dependent pathways.


METHODS
A population-based case-control study of 572 women with CHD-affected pregnancies and 363 women in the control group was conducted. DNA samples were genotyped for single-nucleotide polymorphisms in three genes encoding for folate pathway enzymes. Maternal lifestyle factor information was obtained using standardized interviews.


RESULTS
Women in the case group were 1.5 times more likely to be obese (body mass index of 30 or higher) compared with those in the control group. Obese women carrying the MTHFR TT genotype were 4.6 times more likely to have an affected pregnancy compared with normal-weight women carrying a CC genotype. Obese women carrying one or two copies of the A allele in the BHMT polymorphism were 1.8 times more likely to have a CHD-affected pregnancy than were normal-weight women carrying a BHMT GG genotype. Among women who smoked, those carrying a TCII CG or GG genotype were 1.8 times more likely to have an affected fetus than were women who smoked and carried a CC genotype. Among women who drank alcohol, those carrying a TCII CG or GG genotype were 1.7 times more likely to have an affected fetus than were women who drank and carried a CC genotype.


CONCLUSIONS
Results indicate that functional polymorphisms in folate-related genes increase the risk of having a fetus with CHD when maternal lifestyle factors that alter folate metabolism are present.


METHODS
II.
Hobbs
Charlotte A
CA
From the University of Arkansas for Medical Sciences, College of Medicine, Department of Pediatrics, Birth Defects Research Section, Arkansas Children's Hospital Research Institute, Little Rock, Arkansas.
Cleves
Mario A
MA
Karim
Mohammad A
MA
Zhao
Weizhi
W
MacLeod
Stewart L
SL
D000328:Adult; D000428:Alcohol Drinking / Q000009:adverse effects*; D050940:Betaine-Homocysteine S-Methyltransferase / Q000235:genetics; D016022:Case-Control Studies; D005260:Female; D005492:Folic Acid / Q000235:genetics* / Q000378:metabolism; D006330:Heart Defects, Congenital / Q000235:genetics*; D006801:Humans; D008019:Life Style; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics; D009765:Obesity / Q000150:complications / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D011247:Pregnancy; D012907:Smoking / Q000009:adverse effects*; D014155:Transcobalamins / Q000235:genetics
D014155:Transcobalamins; D005492:Folic Acid; D042965:Methylenetetrahydrofolate Reductase (NADPH2); D050940:Betaine-Homocysteine S-Methyltransferase