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

Huang, Rae-Chi, Galati, John C, Burrows, Sally, Beilin, Lawrence J, Li, Xin, Pennell, Craig E, van Eekelen, JAM, Mori, Trevor A, Adams, Leon A and Craig, Jeffrey M 2012, DNA methylation of the IGF2/H19 imprinting control region and adiposity distribution in young adults, Clinical epigenetics, vol. 4, pp. 1-11, doi: 10.1186/1868-7083-4-21.

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Title DNA methylation of the IGF2/H19 imprinting control region and adiposity distribution in young adults
Author(s) Huang, Rae-Chi
Galati, John C
Burrows, Sally
Beilin, Lawrence J
Li, Xin
Pennell, Craig E
van Eekelen, JAM
Mori, Trevor A
Adams, Leon A
Craig, Jeffrey M
Journal name Clinical epigenetics
Volume number 4
Article ID 21
Start page 1
End page 11
Total pages 11
Publisher BioMed Central
Place of publication London, Eng.
Publication date 2012-11-13
ISSN 1868-7083
Keyword(s) childhood
fetal programming
DNA methylation
insulin-like growth factor
Raine study
head circumference
science & technology
life sciences & biomedicine
oncology
Summary 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.
Language eng
DOI 10.1186/1868-7083-4-21
HERDC Research category C1 Refereed article in a scholarly journal
Copyright notice ©2012, Huang et al.
Free to Read? Yes
Use Rights Creative Commons Attribution licence
Persistent URL http://hdl.handle.net/10536/DRO/DU:30110735

Document type: Journal Article
Collections: School of Medicine
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Every reasonable effort has been made to ensure that permission has been obtained for items included in DRO. If you believe that your rights have been infringed by this repository, please contact drosupport@deakin.edu.au.