Early-life determinants of hypoxia-inducible factor 3A gene (HIF3A) methylation: a birth cohort study

Clinical Epigenetics

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[1] 0000 0000 9442 535X, grid.1058.c, Murdoch Children’s Research Institute, Parkville, Australia;0000 0000 9442 535X, grid.1058.c, Murdoch Children’s Research Institute, Parkville, Australia;0000 0001 0526 7079, grid.1021.2, School of Medicine, Deakin University, Geelong, Australia;0000 0004 0540 0062, grid.414257.1, Child Health Research Unit, Barwon Health, Geelong, Australia;0000 0000 9442 535X, grid.1058.c, Murdoch Children’s Research Institute, Parkville, Australia;0000 0001 2179 088X, grid.1008.9, Department of Paediatrics, University of Melbourne, Parkville, Australia;0000 0000 9442 535X, grid.1058.c, Murdoch Children’s Research Institute, Parkville, Australia;0000 0001 2179 088X, grid.1008.9, Department of Paediatrics, University of Melbourne, Parkville, Australia;0000 0004 0606 5526, grid.418025.a, The Florey Institute of Neuroscience and Mental Health, Parkville, Australia;0000 0000 9442 535X, grid.1058.c, Murdoch Children’s Research Institute, Parkville, Australia;0000 0001 2179 088X, grid.1008.9, Department of Paediatrics, University of Melbourne, Parkville, Australia;0000 0004 1936 7857, grid.1002.3, Department of Paediatrics, Monash University, Clayton, Australia;0000 0000 9442 535X, grid.1058.c, Murdoch Children’s Research Institute, Parkville, Australia;0000 0004 1936 7857, grid.1002.3, School of Public Health & Preventive Medicine, Monash University, Melbourne, Australia;

关键词: HIF3A;    DNA methylation;    SNPs;    Pregnancy;    Infant;    Gestational diabetes;    Pre-eclampsia;   

DOI  :  10.1186/s13148-019-0687-0

来源: publisher

【 摘 要 】

BackgroundMethylation of the hypoxia-inducible factor 3α gene (HIF3A) has been linked to pregnancy exposures, infant adiposity and later BMI. Genetic variation influences HIF3A methylation levels and may modify these relationships. However, data in very early life are limited, particularly in association with adverse pregnancy outcomes. We investigated the relationship between maternal and gestational factors, infant anthropometry, genetic variation and HIF3A DNA methylation in the Barwon Infant Study, a population-based birth cohort. Methylation of two previously studied regions of HIF3A were tested in the cord blood mononuclear cells of 938 infants.ResultsNo compelling evidence was found of an association between birth weight, adiposity or maternal gestational diabetes with methylation at the most widely studied HIF3A region. Male sex (− 4.3%, p < 0.001) and pre-eclampsia (− 5.4%, p = 0.02) negatively associated with methylation at a second region of HIF3A; while positive associations were identified for gestational diabetes (4.8%, p = 0.01) and gestational age (1.2% increase per week, p < 0.001). HIF3A genetic variation also associated strongly with methylation at this region (p < 0.001).ConclusionsPre- and perinatal factors impact HIF3A methylation, including pre-eclampsia. This provides evidence that specific pregnancy complications, previously linked to adverse outcomes for both mother and child, impact the infant epigenome in a molecular pathway critical to several vascular and metabolic conditions. Further work is required to understand the mechanisms and clinical relevance, particularly the differing effects of in utero exposure to gestational diabetes or pre-eclampsia.

【 授权许可】

CC BY