Open Access Research

DNA methylation of the IGF2/H19 imprinting control region and adiposity distribution in young adults

Rae-Chi Huang1237*, John C Galati45, Sally Burrows1, Lawrence J Beilin1, Xin Li5, Craig E Pennell3, JAM van Eekelen3, Trevor A Mori1, Leon A Adams13 and Jeffrey M Craig6

Author Affiliations

1 School of Medicine and Pharmacology, University of Western Australia (UWA), Perth, WA, Australia

2 School of Paediatrics and Child Health Research, (UWA), Perth, WA, Australia

3 Telethon Institute for Child Health Research, (UWA), Perth, WA, Australia

4 Clinical Epidemiology and Biostatistics Unit, Murdoch Children’s Research Institute (MCRI), Royal Children’s Hospital, Melbourne, VIC, Australia

5 Department of Mathematics and Statistics, La Trobe University, Melbourne, VIC, 3086, Australia

6 Early Life Epigenetics Group, MCRI and Department of Paediatrics, University of Melbourne, Royal Children’s Hospital, Melbourne, VIC, Australia

7 Medical Research Foundation Building, Level 4, Rear 50 Murray Street, Perth, WA, 6000, Australia

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Clinical Epigenetics 2012, 4:21  doi:10.1186/1868-7083-4-21

Published: 13 November 2012

Abstract

Background

The insulin-like growth factor 2 (IGF2) and H19 imprinted genes control growth and body composition. Adverse in-utero environments have been associated with obesity-related diseases and linked with altered DNA methylation at the IGF2/H19 locus. Postnatally, methylation at the IGF2/H19 imprinting control region (ICR) has been linked with cerebellum weight. We aimed to investigate whether decreased IGF2/H19 ICR methylation is associated with decreased birth and childhood anthropometry and increased contemporaneous adiposity.

DNA methylation in peripheral blood (n = 315) at 17 years old was measured at 12 cytosine-phosphate-guanine sites (CpGs), analysed as Sequenom MassARRAY EpiTYPER units within the IGF2/H19 ICR. Birth size, childhood head circumference (HC) at six time-points and anthropometry at age 17 years were measured. DNA methylation was investigated for its association with anthropometry using linear regression.

Results

The principal component of IGF2/H19 ICR DNA methylation (representing mean methylation across all CpG units) positively correlated with skin fold thickness (at four CpG units) (P-values between 0.04 to 0.001) and subcutaneous adiposity (P = 0.023) at age 17, but not with weight, height, BMI, waist circumference or visceral adiposity. IGF2/H19 methylation did not associate with birth weight, length or HC, but CpG unit 13 to 14 methylation was negatively associated with HC between 1 and 10 years. β-coefficients of four out of five remaining CpG units also estimated lower methylation with increasing childhood HC.

Conclusions

As greater IGF2/H19 methylation was associated with greater subcutaneous fat measures, but not overall, visceral or central adiposity, we hypothesize that obesogenic pressures in youth result in excess fat being preferentially stored in peripheral fat depots via the IGF2/H19 domain. Secondly, as IGF2/H19 methylation was not associated with birth size but negatively with early childhood HC, we hypothesize that the HC may be a more sensitive marker of early life programming of the IGF axis and of fetal physiology than birth size. To verify this, investigations of the dynamics of IGF2/H19 methylation and expression from birth to adolescence are required.

Keywords:
Childhood; Fetal programming; DNA methylation; Insulin-like growth factor; Raine Study; Head circumference