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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 [email protected])
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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.

References

1.Huxley, R, Owen, CG, Whincup, PH, et al. Is birth weight a risk factor for ischemic heart disease in later life? Am J Clin Nutr. 2007; 85, 1244–1250.CrossRefGoogle ScholarPubMed
2.Huxley, RR, Shiell, AW, Law, CM. The role of size at birth and postnatal catch-up growth in determining systolic blood pressure: a systematic review of the literature. J Hypertens. 2000; 18, 815–831.CrossRefGoogle ScholarPubMed
3.Whincup, PH, Kaye, SJ, Owen, CG, et al. Birth weight and risk of type 2 diabetes: a systematic review. J Am Med Assoc. 2008; 300, 2886–2897.Google ScholarPubMed
4.de Rooij, SR, Painter, RC, Roseboom, TJ, et al. Glucose tolerance at age 58 and the decline of glucose tolerance in comparison with age 50 in people prenatally exposed to the Dutch famine. Diabetologia. 2006; 49, 637–643.CrossRefGoogle Scholar
5.Ravelli, AC, van der Meulen, JH, Michels, RP, et al. Glucose tolerance in adults after prenatal exposure to famine. Lancet. 1998; 351, 173–177.CrossRefGoogle ScholarPubMed
6.Roseboom, TJ, van der Meulen, JH, Osmond, C, et al. Plasma lipid profiles in adults after prenatal exposure to the Dutch famine. Am J Clin Nutr. 2000; 72, 1101–1106.CrossRefGoogle Scholar
7.Painter, RC, de Rooij, SR, Bossuyt, PM, et al. Early onset of coronary artery disease after prenatal exposure to the Dutch famine. Am J Clin Nutr. 2006; 84, 322–327.CrossRefGoogle Scholar
8.Roseboom, TJ, van der Meulen, JH, Osmond, C, et al. Coronary heart disease after prenatal exposure to the Dutch famine, 1944–45. Heart. 2000; 84, 595–598.CrossRefGoogle Scholar
9.Painter, RC, de Rooij, SR, Bossuyt, PM, et al. A possible link between prenatal exposure to famine and breast cancer: a preliminary study. Am J Hum Biol. 2006; 18, 853–856.CrossRefGoogle ScholarPubMed
10.Burdge, GC, Slater-Jefferies, J, Torrens, C, et al. Dietary protein restriction of pregnant rats in the F0 generation induces altered methylation of hepatic gene promoters in the adult male offspring in the F1 and F2 generations. Br J Nutr. 2007; 97, 435–439.CrossRefGoogle ScholarPubMed
11.Lillycrop, KA, Phillips, ES, Jackson, AA, et al. Dietary protein restriction of pregnant rats induces and folic acid supplementation prevents epigenetic modification of hepatic gene expression in the offspring. J Nutr. 2005; 135, 1382–1386.CrossRefGoogle ScholarPubMed
12.Heijmans, BT, Tobi, EW, Stein, AD, et al. Persistent epigenetic differences associated with prenatal exposure to famine in humans. Proc Natl Acad Sci U S A. 2008; 105, 17046–17049.CrossRefGoogle ScholarPubMed
13.Tobi, EW, Lumey, LH, Talens, RP, et al. DNA methylation differences after exposure to prenatal famine are common and timing- and sex-specific. Hum Mol Genet. 2009; 18, 4046–4053.CrossRefGoogle ScholarPubMed
14.Mathers, JC, Strathdee, G, Relton, CL. Induction of epigenetic alterations by dietary and other environmental factors. Adv Genet. 2010; 71, 3–39.CrossRefGoogle ScholarPubMed
15.Lussana, F, Painter, RC, Ocke, MC, et al. Prenatal exposure to the Dutch famine is associated with a preference for fatty foods and a more atherogenic lipid profile. Am J Clin Nutr. 2008; 88, 1648–1652.CrossRefGoogle Scholar
16.Auwerx, J. PPARgamma, the ultimate thrifty gene. Diabetologia. 1999; 42, 1033–1049.CrossRefGoogle ScholarPubMed
17.Forbes, K, Westwood, M. Maternal growth factor regulation of human placental development and fetal growth. J Endocrinol. 2010; 207, 1–16.CrossRefGoogle ScholarPubMed
18.Mead, JR, Irvine, SA, Ramji, DP. Lipoprotein lipase: structure, function, regulation, and role in disease. J Mol Med. 2002; 80, 753–769.CrossRefGoogle ScholarPubMed
19.Lillycrop, KA, Slater-Jefferies, JL, Hanson, MA, et al. Induction of altered epigenetic regulation of the hepatic glucocorticoid receptor in the offspring of rats fed a protein-restricted diet during pregnancy suggests that reduced DNA methyltransferase-1 expression is involved in impaired DNA methylation and changes in histone modifications. Br J Nutr. 2007; 97, 1064–1073.CrossRefGoogle ScholarPubMed
20.Gluckman, PD, Lillycrop, KA, Vickers, MH, et al. Metabolic plasticity during mammalian development is directionally dependent on early nutritional status. Proc Natl Acad Sci U S A. 2007; 104, 12796–12800.CrossRefGoogle ScholarPubMed
21.Ozanne, SE, Jensen, CB, Tingey, KJ, et al. Low birth weight is associated with specific changes in muscle insulin-signaling protein expression. Diabetologia. 2005; 48, 547–552.CrossRefGoogle Scholar
22.Burdge, GC, Slater-Jeffries, JL, Grant, RA, et al. Sex, but no maternal protein or folic acid intake, determines the fatty acid composition of hepatic phospholipids, but not of triacylglycerol, in adult rats. Prostaglandins Leukot Essent Fatty Acids. 2008; 78, 73–79.CrossRefGoogle Scholar
23.Painter, RC, de Rooij, SR, Hutten, BA, et al. Reduced intima media thickness in adults after prenatal exposure to the Dutch famine. Atherosclerosis. 2007; 193, 421–427.CrossRefGoogle Scholar
24.Trienekens, G. Tussen ons volk en de honger. Utrecht: Matrijs. 1985.Google Scholar
25.de Rooij, SR, Painter, RC, Philips, DI, et al. Impaired insulin secretion after prenatal exposure to the Dutch famine. Diabetes Care. 2006; 29, 1897–1901.CrossRefGoogle Scholar
26.World Health Organization. Definition, Diagnosis and Classification of Diabetes Mellitus and its Complications. Report of a WHO Consultation. Part 1, Diagnosis and Classification, 1999. Geneva: World Health Organization.Google Scholar
27.Rose, GA. The diagnosis of ischaemic heart pain and intermittent claudication in field surveys. Bull World Health Organ. 1962; 27, 645–658.Google ScholarPubMed
28.Zigmond, AS, Snaith, RP. The hospital anxiety and depression scale. Acta Psychiatr Scand. 1983; 67, 361–370.CrossRefGoogle ScholarPubMed
29.Bakker, B, Sieben, I. Maten voor prestige, sociaal-economische status en sociale klasse voor de standaard beroepenclassificatie 1992. Sociale Wetenschappen. 1997; 40, 1–22.Google Scholar
30.Fraga, MF, Ballestar, E, Paz, MF, et al. Epigenetic differences arise during the lifetime of monozygotic twins. Proc Natl Acad Sci U S A. 2005; 102, 10604–10609.CrossRefGoogle ScholarPubMed
31.Byun, HM, Siegmund, KD, Pan, F, et al. Epigenetic profiling of somatic tissues from human autopsy specimens identifies tissue- and individual-specific DNA methylation patterns. Hum Mol Genet. 2009; 18, 4808–4817.CrossRefGoogle ScholarPubMed
32.Ollikainen, M, Smith, KR, Joo, EJ, et al. DNA methylation analysis of multiple tissues from newborn twins reveals both genetic and intrauterine components to variation in the human neonatal epigenome. Hum Mol Genet. 2010; 19, 4176–4188.CrossRefGoogle ScholarPubMed
33.Godfrey, KM, Sheppard, A, Gluckman, PD, et al. Epigenetic promoter methylation at birth is associated with child's later adipositiy. Diabetes. 2011; 60, 1528–1534.CrossRefGoogle Scholar
34.Burdge, GC, Lillycrop, KA, Phillips, ES, et al. Folic acid supplementation during the juvenile-pubertal period in rats modifies the phenotype and epigenotype induced by prenatal nutrition. J Nutr. 2009; 139, 1054–1060.CrossRefGoogle ScholarPubMed
35.Lillycrop, KA, Phillips, ES, Torrens, C, et al. Feeding pregnant rats a protein-restricted diet persistently alters the methylation of specific cytosines in the hepatic PPAR alpha promoter of the offspring. Br J Nutr. 2008; 100, 278–282.CrossRefGoogle ScholarPubMed
36.Turner, JD, Pelascini, LP, Macedo, JA, et al. Highly individual methylation patterns of alternative glucocorticoid receptor promoters suggest individualized epigenetic regulatory mechanisms. Nucleic Acids Res. 2008; 36, 7207–7218.CrossRefGoogle ScholarPubMed
37.Liu, H, Zhou, Y, Boggs, SE, et al. Cigarette smoke induces demethylation of prometastatic oncogene synuclein-gamma in lung cancer cells by downregulation of DNMT3B. Oncogene. 2007; 26, 5900–5910.CrossRefGoogle ScholarPubMed
38.Breitling, LP, Yang, R, Korn, B, et al. Tobacco-smoking-related differential DNA methylation: 27K discovery and replication. Am J Hum Genet. 2011; 88, 450–457.CrossRefGoogle ScholarPubMed
39.Launay, JM, Del, PM, Chironi, G, et al. Smoking induces long-lasting effects through a monoamine-oxidase epigenetic regulation. PLoS One. 2009; 4, e7959.CrossRefGoogle ScholarPubMed
40.de Rooij, SR, Costello, PM, Veenendaal, MV, et al. Associations between DNA methylation of a glucocorticoid receptor promoter and acute stress responses in a large healthy adult population are largely explained by lifestyle and educational differences. Psychoneuroendocrinology. 2012; 37, 782–788.CrossRefGoogle Scholar
41.Relton, CM, Groom, A, St. Pourcain, B, et al. DNA methylation patterns in cord blood DNA and body size in childhood. PLoS. 2012; 7, e31821.CrossRefGoogle ScholarPubMed