Maternal DNA hypomethylation and congenital heart defects
Published Date:Jan 19 2011
Source:Birth Defects Res A Clin Mol Teratol. 91(2):69-76.
Congenital Heart Defects
Gene Expression Regulation, Developmental
Heart Defects, Congenital
Long Interspersed Nucleotide Elements
Polymerase Chain Reaction
Pubmed Central ID:PMC3168545
Funding:3U50DD613236-10W1/DD/NCBDD CDC HHS/United States
5-R01-HD039054-08/HD/NICHD NIH HHS/United States
R01 HD039054/HD/NICHD NIH HHS/United States
R01 HD039054-08/HD/NICHD NIH HHS/United States
Congenital heart defects (CHDs) are among the most prevalent and serious of birth defects. Multiple maternal factors are thought to contribute to CHD development including folate intake. Maternal DNA methylation, which is dependent on folate metabolism, may impact the risk of CHDs.
Our study was designed to determine whether maternal long interspersed nucleotide elements-1 (LINE-1) DNA hypomethylation is associated with increased occurrence of non-syndromic CHDs and whether maternal folate-dependent metabolites are correlated with DNA methylation status.
Using a case-control study design, we measured global DNA methylation status among mothers whose pregnancies were affected by non-syndromic CHDs (n=180) and mothers of unaffected pregnancies (n=187). Methylation of LINE-1 was used as a surrogate marker of global DNA methylation status. The association between DNA methylation and CHD risk was determined while adjusting for selected lifestyle factors.
LINE-1 DNA methylation was significantly lower in cases compared with controls (p=0.049). After covariate adjustments, a significant difference between cases and controls remained (p=0.010). Among women with LINE-1 methylation in the lowest decile of DNA methylation, the estimated risk of having a CHD-affected pregnancy was almost twice that of women in all other deciles (OR=1.91; 95% CI: 1.03, 3.58).
Our findings indicate that maternal LINE-1 DNA hypomethylation is associated with an increased risk of CHDs. Future studies investigating the association between maternal DNA methylation patterns and CHDs should be pursued.
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