Variants of folate metabolism genes and risk of left-sided cardiac defects.
BACKGROUND
Congenital heart defects (CHDs) are the most common, serious group of birth defects. Although relatively little is known about the causes of these conditions and there are no established prevention strategies, evidence suggests that the risk of CHDs may be related to maternal folate status as well as genetic variants in folate-related genes. Efforts to establish the relationships between these factors and CHD risk have, however, been hampered by a number of factors, including small study sample sizes and phenotypic heterogeneity.


METHODS
The present study examined the relationship between nine genetic variants in eight folate-related genes and a relatively homogeneous group of left-sided cardiac defects in a cohort of 386 case-parent triads. Log-linear analyses were used to assess both maternal and inherited genetic effects.


RESULTS
Analyses of the study data provided marginal evidence that the maternal MTR A2756G (unadjusted p = 0.01) and the inherited BHMT G742A (unadjusted p = 0.06) genotypes influence the risk of this subset of CHDs. However, neither association achieved significance when the false-discovery rate was controlled at 0.05.


CONCLUSIONS
These results, which are based on the largest study sample and most comprehensive assessment of the relationship between left-sided cardiac defects and folate-related genes reported to date, provide little evidence that this subset of CHDs is folate related. However, even larger studies and more comprehensive evaluations of the folate pathway genes are required to fully explore the relationship between folate and left-sided cardiac defects.
Mitchell
Laura E
LE
Institute of Biosciences and Technology, Texas A&M University System Health Science Center, Houston, Texas, USA.
Long
Jin
J
Garbarini
Jennifer
J
Paluru
Prasuna
P
Goldmuntz
Elizabeth
E
D050940:Betaine-Homocysteine S-Methyltransferase / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D005260:Female; D005492:Folic Acid / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D018636:Hypoplastic Left Heart Syndrome / Q000201:enzymology / Q000235:genetics*; D007223:Infant; D008297:Male; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics*
D005492:Folic Acid; D042965:Methylenetetrahydrofolate Reductase (NADPH2); C494548:BHMT protein, human; D050940:Betaine-Homocysteine S-Methyltransferase