Gestational diabetes and maternal obesity are associated with epigenome-wide methylation changes in children.

Autor: Hjort L; Department of Endocrinology (Diabetes and Metabolism), Rigshospitalet, Copenhagen, Denmark.; Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.; The Danish Diabetes Academy, Odense, Denmark., Martino D; Centre for Food and Allergy Research, Murdoch Children's Research Institute, Melbourne, Victoria, Australia.; Department of Pediatrics, Melbourne University, Melbourne, Victoria, Australia., Grunnet LG; Department of Endocrinology (Diabetes and Metabolism), Rigshospitalet, Copenhagen, Denmark.; The Danish Diabetes Academy, Odense, Denmark., Naeem H; Bioinformatics Group, Murdoch Children's Research Institute, Melbourne, Victoria, Australia.; Monash Bioinformatics Platform, Monash University, Clayton, Victoria, Australia.; Department of Computing and Information Systems, University of Melbourne, Melbourne, Victoria, Australia., Maksimovic J; Department of Pediatrics, Melbourne University, Melbourne, Victoria, Australia.; Bioinformatics Group, Murdoch Children's Research Institute, Melbourne, Victoria, Australia., Olsson AH; Department of Endocrinology (Diabetes and Metabolism), Rigshospitalet, Copenhagen, Denmark., Zhang C; Division of Intramural Population Health Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Rockville, Maryland, USA., Ling C; Epigenetics and Diabetes Unit, Department of Clinical Sciences, Lund University Diabetes Centre, CRC, Scania University Hospital, Malmö, Sweden., Olsen SF; Centre for Fetal Programming, Statens Serum Institut, Copenhagen, Denmark., Saffery R; Department of Pediatrics, Melbourne University, Melbourne, Victoria, Australia.; Cancer and Disease Epigenetics, Murdoch Children's Research Institute, Melbourne, Victoria, Australia., Vaag AA; Department of Endocrinology (Diabetes and Metabolism), Rigshospitalet, Copenhagen, Denmark.; Cardiovascular and Metabolic Disease (CVMD) Translational Medicine Unit, Early Clinical Development, IMED Biotech Unit, AstraZeneca, Gothenburg, Sweden.
Jazyk: angličtina
Zdroj: JCI insight [JCI Insight] 2018 Sep 06; Vol. 3 (17). Date of Electronic Publication: 2018 Sep 06 (Print Publication: 2018).
DOI: 10.1172/jci.insight.122572
Abstrakt: Offspring of women with gestational diabetes mellitus (GDM) are at increased risk of developing metabolic disease, potentially mediated by epigenetic mechanisms. We recruited 608 GDM and 626 control offspring from the Danish National Birth Cohort, aged between 9 and 16 years. DNA methylation profiles were measured in peripheral blood of 93 GDM offspring and 95 controls using the Illumina HumanMethylation450 BeadChip. Pyrosequencing was performed for validation/replication of putative GDM-associated, differentially methylated CpGs in additional 905 offspring (462 GDM, 444 control offspring). We identified 76 differentially methylated CpGs in GDM offspring compared with controls in the discovery cohort (FDR, P < 0.05). Adjusting for offspring BMI did not affect the association between methylation levels and GDM status for any of the 76 CpGs. Most of these epigenetic changes were due to confounding by maternal prepregnancy BMI; however, 13 methylation changes were independently associated with maternal GDM. Three prepregnancy BMI-associated CpGs (cg00992687 and cg09452568 of ESM1 and cg14328641 of MS4A3) were validated in the replication cohort, while cg09109411 (PDE6A) was found to be associated with GDM status. The identified methylation changes may reflect developmental programming of organ disease mechanisms and/or may serve as disease biomarkers.
Databáze: MEDLINE