title: Epigenome-wide and transcriptome-wide analyses reveal gestational diabetes is associated with alterations in the human leukocyte antigen complex.
abstract: BACKGROUND
  Gestational diabetes mellitus (GDM) affects approximately 10 % of pregnancies in the United States and increases the risk of adverse health outcomes in the offspring. These adult disease propensities may be set by anatomical and molecular alterations in the placenta associated with GDM.
  
  
  RESULTS
  To assess the mechanistic aspects of fetal programming, we measured genome-wide methylation (Infinium HumanMethylation450 BeadChips) and expression (Affymetrix transcriptome microarrays) in placental tissue of 41 GDM cases and 41 matched pregnancies without maternal complications from the Harvard Epigenetic Birth Cohort. Specific transcriptional and epigenetic perturbations associated with GDM status included alterations in the major histocompatibility complex (MHC) region, which were validated in an independent cohort, the Rhode Island Child Health Study. Gene ontology enrichment among gene regulation influenced by GDM revealed an over-representation of immune response pathways among differential expression, reflecting these coordinated changes in the MHC region. This differential methylation and expression may be capturing shifts in cellular composition, reflecting physiological changes in the placenta associated with GDM.
  
  
  CONCLUSIONS
  Our study represents the largest investigation of transcriptomic and methylomic differences associated with GDM, providing comprehensive insight into how GDM shapes the intrauterine environment, which may have implications for fetal (re)programming.
authors.affiliation: Department of Epidemiology, Harvard School of Public Health, Boston, MA 02115 USA.
authors.forename: Alexandra M
authors.initials: AM
authors.lastname: Binder
authors.affiliation: Harvard University Center for the Environment, Harvard University, Cambridge, MA 02138 USA ; Obstetrics and Gynecology Epidemiology Center, Department of Obstetrics, Gynecology, and Reproductive Biology, Brigham and Women's Hospital, Harvard Medical School, 221 Longwood Ave., Boston, MA 02115 USA.
authors.forename: Jessica
authors.initials: J
authors.lastname: LaRocca
authors.affiliation: Department of Pharmacology and Toxicology, and Section of Biostatistics and Epidemiology, Department of Community and Family Medicine, Geisel School of Medicine at Dartmouth, Hanover, NH 03755 USA.
authors.forename: Corina
authors.initials: C
authors.lastname: Lesseur
authors.affiliation: Department of Pharmacology and Toxicology, and Section of Biostatistics and Epidemiology, Department of Community and Family Medicine, Geisel School of Medicine at Dartmouth, Hanover, NH 03755 USA.
authors.forename: Carmen J
authors.initials: CJ
authors.lastname: Marsit
authors.affiliation: Department of Epidemiology, Harvard School of Public Health, Boston, MA 02115 USA ; Harvard University Center for the Environment, Harvard University, Cambridge, MA 02138 USA ; Obstetrics and Gynecology Epidemiology Center, Department of Obstetrics, Gynecology, and Reproductive Biology, Brigham and Women's Hospital, Harvard Medical School, 221 Longwood Ave., Boston, MA 02115 USA.
authors.forename: Karin B
authors.initials: KB
authors.lastname: Michels
keywords: Gestational diabetes; Human leukocyte antigen; Methylome; Transcriptome