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Prenatal famine exposure, health in later life and promoter methylation of four candidate genes

Published online by Cambridge University Press:  09 July 2012

M. V. Veenendaal ,
P. M. Costello ,
K. A. Lillycrop ,
S. R. de Rooij ,
J. A. van der Post ,
P. M. Bossuyt ,
M. A. Hanson ,
R. C. Painter  and
T. J. Roseboom
M. V. Veenendaal*
Affiliation:
Department of Clinical Epidemiology and Biostatistics, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands
P. M. Costello
Affiliation:
Academic Unit of Human Development and Health, Faculty of Medicine, University of Southampton, UK
K. A. Lillycrop
Affiliation:
Faculty of Natural and Environmental Sciences, University of Southampton, Southampton, UK
S. R. de Rooij
Affiliation:
Department of Clinical Epidemiology and Biostatistics, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands
J. A. van der Post
Affiliation:
Department of Obstetrics and Gynaecology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands
P. M. Bossuyt
Affiliation:
Department of Clinical Epidemiology and Biostatistics, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands
M. A. Hanson
Affiliation:
Academic Unit of Human Development and Health, Faculty of Medicine, University of Southampton, UK
R. C. Painter
Affiliation:
Department of Obstetrics and Gynaecology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands
T. J. Roseboom
Affiliation:
Department of Clinical Epidemiology and Biostatistics, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands
*
*Address for correspondence: Dr M. Veenendaal, Department of Clinical Epidemiology, Biostatistics and Bioinformatics, Academic Medical Center, PO Box 22660, 1100 DD Amsterdam, The Netherlands. (Email m.v.veenendaal@amc.uva.nl)
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Abstract

Poor nutrition during fetal development can permanently alter growth, cardiovascular physiology and metabolic function. Animal studies have shown that prenatal undernutrition followed by balanced postnatal nutrition alters deoxyribonucleic acid (DNA) methylation of gene promoter regions of candidate metabolic control genes in the liver. The aim of this study was to investigate whether methylation status of the proximal promoter regions of four candidate genes differed between individuals exposed to the Dutch famine in utero. In addition, we determined whether methylation status of these genes was associated with markers of metabolic and cardiovascular disease and adult lifestyle. Methylation status of the GR1-C (glucocorticoid receptor), PPARγ (peroxisome proliferator-activated receptor gamma), lipoprotein lipase and phosphatidylinositol 3 kinase p85 proximal promoters was investigated in DNA isolated from peripheral blood samples of 759 58-year-old subjects born around the time of the 1944–45 Dutch famine. We observed no differences in methylation levels of the promoters between exposed and unexposed men and women. Methylation status of PPARγ was associated with levels of high-density lipoprotein cholesterol and triglycerides as well as with exercise and smoking. Hypomethylation of the GR promoter was associated with adverse adult lifestyle factors, including higher body mass index, less exercise and more smoking. The previously reported increased risk of cardiovascular and metabolic disease after prenatal famine exposure was not associated with differences in methylation status across the promoter regions of these candidate genes measured in peripheral blood. The adult environment seems to affect GR and PPARγ promoter methylation.

Keywords

epigeneticsfaminefetal programming
Type
Original Article
Information
Journal of Developmental Origins of Health and Disease , Volume 3 , Issue 6 , December 2012 , pp. 450 - 457
Copyright
Copyright © Cambridge University Press and the International Society for Developmental Origins of Health and Disease 2012 

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Footnotes

†

Both authors contributed equally to this work.

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