title: Insulin-like growth factor 2/H19 methylation at birth and risk of overweight and obesity in children.
abstract: OBJECTIVE
  To determine whether aberrant DNA methylation at differentially methylated regions (DMRs) regulating insulin-like growth factor 2 (IGF2) expression in umbilical cord blood is associated with overweight or obesity in a multiethnic cohort.
  
  
  METHODS
  Umbilical cord blood leukocytes of 204 infants born between 2005 and 2009 in Durham, North Carolina, were analyzed for DNA methylation at two IGF2 DMRs by using pyrosequencing. Anthropometric and feeding data were collected at age 1 year. Methylation differences were compared between children >85th percentile of the Centers for Disease Control and Prevention growth charts weight-for-age (WFA) and children ≤ 85th percentile of WFA at 1 year by using generalized linear models, adjusting for post-natal caloric intake, maternal cigarette smoking, and race/ethnicity.
  
  
  RESULTS
  The methylation percentages at the H19 imprint center DMR was higher in infants with WFA >85th percentile (62.7%; 95% CI, 59.9%-65.5%) than in infants with WFA ≤ 85th percentile (59.3%; 95% CI, 58.2%-60.3%; P = .02). At the intragenic IGF2 DMR, methylation levels were comparable between infants with WFA ≤ 85th percentile and infants with WFA >85th percentile.
  
  
  CONCLUSIONS
  Our findings suggest that IGF2 plasticity may be mechanistically important in early childhood overweight or obese status. If confirmed in larger studies, these findings suggest aberrant DNA methylation at sequences regulating imprinted genes may be useful identifiers of children at risk for the development of early obesity.
authors.affiliation: Department of Community and Family Medicine, Duke University, Durham, NC 27710, USA.
authors.forename: Ellen
authors.initials: E
authors.lastname: Perkins
authors.forename: Susan K
authors.initials: SK
authors.lastname: Murphy
authors.forename: Amy P
authors.initials: AP
authors.lastname: Murtha
authors.forename: Joellen
authors.initials: J
authors.lastname: Schildkraut
authors.forename: Randy L
authors.initials: RL
authors.lastname: Jirtle
authors.forename: Wendy
authors.initials: W
authors.lastname: Demark-Wahnefried
authors.forename: Michele R
authors.initials: MR
authors.lastname: Forman
authors.forename: Joanne
authors.initials: J
authors.lastname: Kurtzberg
authors.forename: Francine
authors.initials: F
authors.lastname: Overcash
authors.forename: Zhiqing
authors.initials: Z
authors.lastname: Huang
authors.forename: Cathrine
authors.initials: C
authors.lastname: Hoyo
mesh_terms: D019175:DNA Methylation; D005260:Female; D006801:Humans; D007223:Infant; D007335:Insulin-Like Growth Factor II / Q000235:genetics*; D008297:Male; D009765:Obesity / Q000235:genetics*; D050177:Overweight / Q000235:genetics*; D011446:Prospective Studies; D012306:Risk
chemical_list: D007335:Insulin-Like Growth Factor II