title: Association of cord blood methylation fractions at imprinted insulin-like growth factor 2 (IGF2), plasma IGF2, and birth weight.
abstract: OBJECTIVE
  Altered methylation at Insulin-like Growth Factor 2 (IGF2) regulatory regions has previously been associated with obesity, and several malignancies including colon, esophageal, and prostate adenocarcinomas, presumably via changes in expression and/or loss of imprinting, but the functional significance of these DNA methylation marks have not been demonstrated in humans. We examined associations among DNA methylation at IGF2 differentially methylated regions (DMRs), circulating IGF2 protein concentrations in umbilical cord blood (UCB) and birth weight in newborns.
  
  
  METHODS
  Questionnaire data were obtained from 300 pregnant women recruited between 2005 and 2009. UCB DNA methylation was measured by bisulfite pyrosequencing. UCB plasma concentrations of soluble IGF2 were measured by ELISA assays. Generalized linear regression models were used to examine the relationship between DMR methylation and IGF2 levels.
  
  
  RESULTS
  Lower IGF2 DMR methylation was associated with elevated plasma IGF2 protein concentrations (β = -9.87, p < 0.01); an association that was stronger in infants born to obese women (pre-pregnancy BMI > 30 kg/m(2), β = -20.21, p < 0.0001). Elevated IGF2 concentrations were associated with higher birth weight (p < 0.0001) after adjusting for maternal race/ethnicity, pre-pregnancy BMI, cigarette smoking, gestational diabetes, and infant sex. These patterns of association were not apparent at the H19 DMR.
  
  
  CONCLUSIONS
  Our data suggest that variation in IGF2 DMR methylation is an important mechanism by which circulating IGF2 concentrations, a putative risk factor for obesity and cancers of the colon, esophagus, and prostate, are modulated; associations that may depend on pre-pregnancy obesity.
authors.affiliation: Department of Community and Family Medicine, Duke University Medical Center, 2200 West Main Street, Ste. 600, Durham, NC 27705, USA. cathrine.hoyo@duke.edu
authors.forename: Cathrine
authors.initials: C
authors.lastname: Hoyo
authors.forename: Kimberly
authors.initials: K
authors.lastname: Fortner
authors.forename: Amy P
authors.initials: AP
authors.lastname: Murtha
authors.forename: Joellen M
authors.initials: JM
authors.lastname: Schildkraut
authors.forename: Adelheid
authors.initials: A
authors.lastname: Soubry
authors.forename: Wendy
authors.initials: W
authors.lastname: Demark-Wahnefried
authors.forename: Randy L
authors.initials: RL
authors.lastname: Jirtle
authors.forename: Joanne
authors.initials: J
authors.lastname: Kurtzberg
authors.forename: Michele R
authors.initials: MR
authors.lastname: Forman
authors.forename: Francine
authors.initials: F
authors.lastname: Overcash
authors.forename: Zhiqing
authors.initials: Z
authors.lastname: Huang
authors.forename: Susan K
authors.initials: SK
authors.lastname: Murphy
mesh_terms: D001724:Birth Weight / Q000235:genetics*; D019175:DNA Methylation / Q000235:genetics*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005312:Fetal Blood; D018392:Genomic Imprinting; D006801:Humans; D007231:Infant, Newborn; D007335:Insulin-Like Growth Factor II / Q000032:analysis / Q000235:genetics*; D008297:Male
chemical_list: C035170:IGF2 protein, human; D007335:Insulin-Like Growth Factor II