Altered Methylation of IGF2 Locus 20 Years after Preterm Birth at Very Low Birth Weight

Karoliina Wehkalampi; Mari Muurinen; Sara Bruce Wirta; Katariina Hannula-Jouppi; Petteri Hovi; Anna-Liisa Järvenpää; Johan G Eriksson; Sture Andersson; Juha Kere; Eero Kajantie

doi:10.1371/journal.pone.0067379

Altered Methylation of IGF2 Locus 20 Years after Preterm Birth at Very Low Birth Weight

PLoS One. 2013 Jun 19;8(6):e67379. doi: 10.1371/journal.pone.0067379. Print 2013.

Authors

Karoliina Wehkalampi¹, Mari Muurinen, Sara Bruce Wirta, Katariina Hannula-Jouppi, Petteri Hovi, Anna-Liisa Järvenpää, Johan G Eriksson, Sture Andersson, Juha Kere, Eero Kajantie

Affiliation

¹ Department of Health Promotion and Chronic Disease Prevention, National Institute for Health and Welfare, Helsinki, Finland ; Children's Hospital, Helsinki University Central Hospital, Helsinki, Finland.

Abstract

Introduction: People born preterm at very low birth weight (VLBW, ≤1500g) have higher rates of risk factors for adult-onset diseases, including cardiovascular diseases and type 2 diabetes. These risks may be mediated through epigenetic modification of genes that are critical to normal growth and development.

Methods: We measured the methylation level of an imprinted insulin-like-growth-factor 2 (IGF2) locus (IGF2/H19) in young adults born preterm at VLBW and in their peers born at term. We studied 158 VLBW and 161 control subjects aged 18 to 27 years from the Helsinki Study of Very Low Birth Weight Adults. Methylation fraction at two IGF2 differentially methylated regions (DMRs) - IGF2 antisense transcript (IGF2AS, also known as IGF2 DMR0) and last exon of IGF2 (IGF2_05, also known as IGF2 DMR2) - were measured with Sequenom Epityper. We used linear regression and adjustment for covariates to compare methylation fractions at these DMRs between VLBW and control subjects.

Results: At one IGF2AS CpG site, methylation was significantly lower in VLBW than in control subjects, mean difference -0.017 (95% CI; -0.028, -0.005), P = 0.004. Methylation at IGF2_05 was not different between the groups.

Conclusions: Methylation of IGF2AS is altered 20 years after preterm birth at VLBW. Altered methylation may be a mechanism of later increased disease risk but more data are needed to indicate causality.

Publication types

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

MeSH terms

Adolescent
Adult
DNA Methylation*
Female
Humans
Infant, Newborn
Infant, Premature*
Infant, Very Low Birth Weight*
Insulin-Like Growth Factor II / genetics*
Male
Risk Factors
Young Adult

Substances

IGF2 protein, human
Insulin-Like Growth Factor II

Grants and funding

The study has been supported by the Academy of Finland, the Novo Nordisk Foundation, the Finnish Foundation for Pediatric Research, the Finnish Medical Foundation, the Yrjö Jahnsson Foundation, the Biomedicum Helsinki Foundation, Finnish Medical Societies (Duodecim and Finska Läkaresällskapet), the Finnish Special Governmental Subsidiary for Health Sciences, the Finnish National Graduate School of Clinical Investigation, Helsinki Biomedical Graduate Program, Swedish Research Council, the Jalmari and Rauha Ahokas Foundation, the Juho Vainio Foundation, the Päivikki and Sakari Sohlberg Foundation, the Signe and Ane Gyllenberg Foundation, the Sigrid Juselius Foundation, the Waldemar von Frenckell Foundation, Vasa Nation and Wiipurilainen Osakunta at Helsinki University. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.