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Epigenomics. 2015;7(6):937-50. doi: 10.2217/epi.15.45. Epub 2015 May 26.

HIF3A association with adiposity: the story begins before birth.

Author information

1
Singapore Institute for Clinical Sciences (SICS), A*STAR, Brenner Centre for Molecular Medicine, 117609, Singapore.
2
School of Computer Engineering, Nanyang Technological University (NTU), 639798, Singapore.
3
Saw Swee Hock School of Public Health, National University of Singapore (NUS), 117597, Singapore.
4
Yong Loo Lin School of Medicine, National University of Singapore (NUS), 119228, Singapore.
5
Division of Paediatric Endocrinology & Diabetes, Khoo Teck Puat-National University Children's Medical Institute, National University Health System, 119228, Singapore.
6
Department of Medical Genetics, Centre for Molecular Medicine & Therapeutics, Child & Family Research Institute, University of British Columbia, Vancouver, BC, V5Z 4H4 Canada.
7
KK Women's and Children's Hospital, 229899, Singapore.
8
Ludmer Centre for Neuroinformatics & Mental Health, Douglas University Mental Health Institute, McGill University, Montreal, (Quebec) H4H 1R3, Canada.
9
MRC Lifecourse Epidemiology Unit & NIHR Southampton Biomedical Research Centre, University of Southampton & University Hospital Southampton NHS Foundation Trust, Southampton, SO16 6YD, UK.
10
Centre for Human Evolution, Adaptation & Disease, Liggins Institute, University of Auckland, Auckland, 1142, New Zealand.

Abstract

AIM:

Determine if the association of HIF3A DNA methylation with weight and adiposity is detectable early in life.

MATERIAL & METHODS:

We determined HIF3A genotype and DNA methylation patterns (on hybridization arrays) in DNA extracted from umbilical cords of 991 infants. Methylation levels at three CpGs in the HIF3A first intron were related to neonatal and infant anthropometry and to genotype at nearby polymorphic sites.

RESULTS & CONCLUSION:

Higher methylation levels at three previously described HIF3A CpGs were associated with greater infant weight and adiposity. The effect sizes were slightly smaller than those reported for adult BMI. There was also an interaction within cis-genotype. The association between higher DNA methylation at HIF3A and increased adiposity is present in neonates. In this study, no particular prenatal factor strongly influenced HIF3A hypermethylation. Our data nonetheless suggest shared prenatal influences on HIF3A methylation and adiposity.

KEYWORDS:

DNA methylation; HIF3A protein; birth weight; embryonic and fetal development; epigenomics; human; obesity

PMID:
26011824
PMCID:
PMC4863876
DOI:
10.2217/epi.15.45
[Indexed for MEDLINE]
Free PMC Article

Conflict of interest statement

Financial & competing interests disclosure KM Godfrey, PD Gluckman and Y-S Chong have received reimbursement for speaking at conferences sponsored by companies selling nutritional products. They are part of an academic consortium that has received research funding from Abbott Nutrition, Nestec and Danone. This work was supported by the Translational Clinical Research (TCR) Flagship Program on Developmental Pathways to Metabolic Disease funded by the National Research Foundation (NRF) and administered by the National Medical Research Council (NMRC), Singapore – NMRC/TCR/004-NUS/2008. Additional funding is provided by the Singapore Institute for Clinical Sciences (SICS) – Agency for Science, Technology and Research (A*STAR), Singapore. KM Godfrey is supported by the National Institute for Health Research through the NIHR Southampton Biomedical Research Centre and by the European Union's Seventh Framework Programme (FP7/2007–2013), project EarlyNutrition under grant agreement no 289346. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript.

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