Hypermethylation at loci sensitive to the prenatal environment is associated with increased incidence of myocardial infarction

Talens, R.P., Jukema, J.W., Trompet, S., Kremer, D., Westendorp, R.G.J., Lumey, L.H., Sattar, N. , Putter, H., Slagboom, P.E. and Heijmans, B.T. (2012) Hypermethylation at loci sensitive to the prenatal environment is associated with increased incidence of myocardial infarction. International Journal of Epidemiology, 41(1), pp. 106-115. (doi:10.1093/ije/dyr153)

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Abstract

Background: Human epidemiological studies suggest that small size at birth and food deprivation during gestation confer an excess risk of coronary heart diseases (CHD) in adulthood, frequently in a sex-specific manner. Prior epigenetic studies indicate that such prenatal conditions are marked by persistent and sometimes sex-specific changes in DNA methylation. Here, we have investigated the association between DNA methylation and myocardial infarction (MI) at six loci sensitive to prenatal nutrition, anticipating potential sex-specificity.

Method: Within the placebo group of the PROSPER trial on pravastatin and the risk of CHD, we compared all individuals who were event free at baseline and developed MI during 3 years' follow-up (n = 122) with a similar-sized control group. Methylation at IL10, LEP, ABCA1, IGF2, INS and GNASAS was measured in DNA extracted from leucocytes using mass spectrometry.

Results: DNA methylation at GNASAS was modestly higher in MI cases compared with controls (P = 0.030). A significant sex interaction was observed for INS (P = 0.014) and GNASAS (P = 0.031). Higher DNA methylation at these loci was associated with MI among women (INS: +2.5%, P = 0.002; GNASAS: +4.2%, P = 0.001). Hypermethylation at one locus and at both loci was associated with odds ratios (ORs) of 2.8 and 8.6, respectively (Ptrend = 3.0 × 10−4). No association was observed among men.

Conclusions: The risk of MI in women is associated with DNA methylation marks at specific loci previously shown to be sensitive to prenatal conditions. This observation may reflect a developmental component of MI.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Sattar, Professor Naveed
Authors: Talens, R.P., Jukema, J.W., Trompet, S., Kremer, D., Westendorp, R.G.J., Lumey, L.H., Sattar, N., Putter, H., Slagboom, P.E., and Heijmans, B.T.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cardiovascular and Medical Sciences
Journal Name:International Journal of Epidemiology
Publisher:Oxford University Press
ISSN:0300-5771
ISSN (Online):1464-3685
Published Online:17 November 2011
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