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

Mansell, Toby, Ponsonby, Anne-Louise, Januar, Vania, Novakovic, Boris, Collier, Fiona, Burgner, David, Vuillermin, Peter, Ryan, Joanne, Saffery, Richard and Barwon Infant Study Investigator Team 2019, Early-life determinants of hypoxia-inducible factor 3A gene (HIF3A) methylation: a birth cohort study, Clinical epigenetics, vol. 11, no. 1, doi: 10.1186/s13148-019-0687-0.

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Title Early-life determinants of hypoxia-inducible factor 3A gene (HIF3A) methylation: a birth cohort study
Author(s) Mansell, Toby
Ponsonby, Anne-Louise
Januar, Vania
Novakovic, Boris
Collier, Fiona
Burgner, David
Vuillermin, PeterORCID iD for Vuillermin, Peter orcid.org/0000-0002-6580-0346
Ryan, Joanne
Saffery, Richard
Barwon Infant Study Investigator Team
Journal name Clinical epigenetics
Volume number 11
Issue number 1
Article ID 96
Total pages 12
Publisher BioMed Central
Place of publication London, Eng.
Publication date 2019-07-01
ISSN 1868-7075
1868-7083
Keyword(s) Science & Technology
Life Sciences & Biomedicine
Oncology
Genetics & Heredity
HIF3A
DNA methylation
SNPs
Pregnancy
Infant
Gestational diabetes
Pre-eclampsia
BODY-MASS INDEX
ADIPOSE-TISSUE
DEVELOPMENTAL ORIGINS
GENE-EXPRESSION
BMI
CIRCUMFERENCE
ASSOCIATION
WEIGHT
Barwon Infant Study Investigator Team
Summary Background: Methylation 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. Results: No 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). Conclusions: Pre- 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.
Language eng
DOI 10.1186/s13148-019-0687-0
Indigenous content off
HERDC Research category C1 Refereed article in a scholarly journal
Copyright notice ©2019, The Authors
Persistent URL http://hdl.handle.net/10536/DRO/DU:30124976

Document type: Journal Article
Collections: Faculty of Health
School of Medicine
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