Methylation variation at IGF2 differentially methylated regions and maternal folic acid use before and during pregnancy.

Journal Article (Journal Article)

Folic acid (FA) supplementation before and during pregnancy has been associated with decreased risk of neural tube defects although recent reports suggest it may also increase the risk of other chronic diseases. We evaluated exposure to maternal FA supplementation before and during pregnancy in relation to aberrant DNA methylation at two differentially methylated regions (DMRs) regulating Insulin-like Growth Factor 2 (IGF2) expression in infants. Aberrant methylation at these regions has been associated with IGF2 deregulation and increased susceptibility to several chronic diseases. Using a self-administered questionnaire, we assessed FA intake before and during pregnancy in 438 pregnant women. Pyrosequencing was used to measure methylation at two IGF2 DMRs in umbilical cord blood leukocytes. Mixed models were used to determine relationships between maternal FA supplementation before or during pregnancy and DNA methylation levels at birth. Average methylation at the H19 DMR was 61.2%. Compared to infants born to women reporting no FA intake before or during pregnancy, methylation levels at the H19 DMR decreased with increasing FA intake (2.8%, p=0.03, and 4.9%, p=0.04, for intake before and during pregnancy, respectively). This methylation decrease was most pronounced in male infants (p=0.01). Methylation alterations at the H19 DMR are likely an important mechanism by which FA risks and/or benefits are conferred in utero. Because stable methylation marks at DMRs regulating imprinted genes are acquired before gastrulation, they may serve as archives of early exposures with the potential to improve our understanding of developmental origins of adult disease.

Full Text

Duke Authors

Cited Authors

  • Hoyo, C; Murtha, AP; Schildkraut, JM; Jirtle, RL; Demark-Wahnefried, W; Forman, MR; Iversen, ES; Kurtzberg, J; Overcash, F; Huang, Z; Murphy, SK

Published Date

  • July 2011

Published In

Volume / Issue

  • 6 / 7

Start / End Page

  • 928 - 936

PubMed ID

  • 21636975

Pubmed Central ID

  • PMC3154433

Electronic International Standard Serial Number (EISSN)

  • 1559-2308

Digital Object Identifier (DOI)

  • 10.4161/epi.6.7.16263


  • eng

Conference Location

  • United States