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Talens, R.P.; Jukema, J.W.; Trompet, S.; Kremer, D.; Westendorp, R.G.J.; Lumey, L.H.; ... ; PROSPER Grp (2011)

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

Article / Letter to editor
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...Show moreBACKGROUND: 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 (P(trend) = 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.Show less
All 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.; Heijmans, B.T.; PROSPER Grp
Date
2011-11-17
Journal
International Journal of Epidemiology
DOI
doi:10.1093/ije/dyr153