Journal
BIRTH DEFECTS RESEARCH PART A-CLINICAL AND MOLECULAR TERATOLOGY
Volume 91, Issue 2, Pages 69-76Publisher
WILEY
DOI: 10.1002/bdra.20761
Keywords
congenital heart defects; DNA methylation; LINE-1; folate; maternal biomarkers
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Funding
- NICHD NIH HHS [R01 HD039054-08, 5-R01-HD039054-08, R01 HD039054] Funding Source: Medline
- NCBDD CDC HHS [U50 DD613236, 3U50DD613236-10W1] Funding Source: Medline
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BACKGROUND: 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. METHODS: 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. RESULTS: LINE-1 DNA methylation was significantly lower in cases compared to 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 (odds ratio [OR], 1.91; 95% confidence interval [CI], 1.03-3.58). CONCLUSIONS: 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. Birth Defects Research (Part A) 91:69-76, 2011. (C) 2011 Wiley-Liss, Inc.
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