Pan H, Lin X, Wu Y, Chen L, Teh AL, Soh SE, Lee YS, Tint MT, MacIsaac JL, Morin AM, Tan KH, Yap F, Saw SM, Kobor MS, Meaney MJ, Godfrey KM, Chong YS, Gluckman PD, Karnani N, Holbrook JD; GUSTO Study Group. “HIF3A association with adiposity: the story begins before birth.” Epigenomics. 2015;7(6):937-50. doi: 10.2217/epi.15.45.
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.
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.