Epigenome-wide and Transcriptome-wide Analyses Reveal Gestational Diabetes is Associated with Alterations in the Human Leukocyte Antigen Complex [methylation]

Gestational diabetes mellitus (GDM) affects approximately 18% 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. 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. Our study represents the largest investigation of transcriptomic and methylomic differences associated with GDM, providing comprehensive insight into the molecular basis of GDM induced fetal (re)programming. Bisulphite converted DNA extracted from the placentas (maternal-side) of 41 clinically-confirmed cases of GDM and 41 pregnancies without maternal complications were hybridised to the Illumina Infinium HumanMethylation450 Beadchips