HIF3A association with adiposity: the story begins before birth

Hong Pan; Xinyi Lin; Yonghui Wu; Li Chen; Ai Ling Teh; Shu E Soh; Yung Seng Lee; Mya Thway Tint; Julia L MacIsaac; Alexander M Morin; Kok Hian Tan; Fabian Yap; Seang Mei Saw; Michael S Kobor; Michael J Meaney; Keith M Godfrey; Yap-Seng Chong; Peter D Gluckman; Neerja Karnani; Joanna D Holbrook; GUSTO Study Group

doi:10.2217/epi.15.45

HIF3A association with adiposity: the story begins before birth

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

Authors

Hong Pan^{1

2}, Xinyi Lin¹, Yonghui Wu¹, Li Chen¹, Ai Ling Teh¹, Shu E Soh^{3

4}, Yung Seng Lee^{1

4

5}, Mya Thway Tint⁴, Julia L MacIsaac⁶, Alexander M Morin⁶, Kok Hian Tan⁷, Fabian Yap⁷, Seang Mei Saw³, Michael S Kobor⁶, Michael J Meaney^{1

8}, Keith M Godfrey⁹, Yap-Seng Chong^{1

4}, Peter D Gluckman^{1

10}, Neerja Karnani^{1

4}, Joanna D Holbrook¹; GUSTO Study Group

Collaborators

GUSTO Study Group:
P Agarwal, A Biswas, C L Bong, B F P Broekman, S Cai, J K Y Chan, Y H Chan, C Y I Chee, H Y H Chen, Y B Cheung, A Chia, A Chinnadurai, C K Chng, M F F Chong, S C Chong, M C Chua, C M Ding, E A Finkelstein, D Fok, M Fortier, A E N Goh, Y T D Goh, J J Gooley, W M Han, M Hanson, C J Henry, C-Y Hsu, H Inskip, J Kapur, K Kwek, I Y-M Lau, B W Lee, N Lek, S B Lim, Y-L Low, I Magiati, L M Daniel, C Ngo, K Naiduvaje, W W Pang, A Qiu, B L Quah, V S Rajadurai, M Rauff, S A Rebello, J L Richmond, A Rifkin-Graboi, L P-C Shek, A Sheppard, B Shuter, L Singh, W Stunkel, L L Su, O H Teoh, H P S van Bever, R M van Dam, I B Y Wong, P C Wong, G S H Yeo

Affiliations

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adiposity / genetics*
Adult
Alleles
Apoptosis Regulatory Proteins
Basic Helix-Loop-Helix Transcription Factors / genetics*
Birth Weight
Child, Preschool
CpG Islands
DNA Methylation*
Environmental Exposure
Epigenesis, Genetic
Female
Gene Expression Regulation
Genotype
Humans
Infant
Infant, Newborn
Male
Maternal Exposure
Polymorphism, Single Nucleotide
Pregnancy
Repressor Proteins
Umbilical Cord / metabolism

Substances

Apoptosis Regulatory Proteins
Basic Helix-Loop-Helix Transcription Factors
HIF3A protein, human
Repressor Proteins

Abstract

Publication types

MeSH terms

Substances

Grants and funding