Association between blood pressure and DNA methylation of retrotransposons and pro-inflammatory genes

作者：Alexeeff Stacey E^*; Baccarelli Andrea A; Halonen Jaana; Coull Brent A; Wright Robert O; Tarantini Letizia; Bollati Valentina; Sparrow David; Vokonas Pantel; Schwartz Joel

来源：International Journal of Epidemiology, 2013, 42(1): 270-280.

DOI：10.1093/ije/dys220

• Epigenetics
• DNA methylation
• blood pressure
• inflammation
• Bayesian model

Background Methylation of deoxyribonucleic acid (DNA) is an epigenetic regulator of gene expression that changes with age, but its contribution to aging-related disorders, including high blood pressure (BP), is still largely unknown. We examined the relation of BP to the methylation of retrotransposon sequences of DNA and of selected candidate genes. %26lt;br%26gt;Methods This investigation included 789 elderly participants in the Normative Aging Study, ranging in age from 55 to 100 years, who had longitudinal measurements of DNA methylation. In these subjects%26apos; DNA we measured the proportion of methylated sites in retrotransposable sequences and in pro-inflammatory genes, expressed as the percent of 5-methylated cytosines (%5mC) among all cytosines. From one to four methylation measurements were made for each subject between 1999 and 2009. We fit mixed-effects models, using repeated measures of BP as the outcome and DNA methylation as the explanatory variable, adjusting for confounding variables. We also fit a Bayesian mixed-effects structural equation model to account for heterogeneity in the effects of methylation sites within each gene. %26lt;br%26gt;Results An increase in inter-quartile range (IQR) in the methylation of Alu elements was associated with an increase of 0.97 mm Hg in diastolic blood pressure (DBP) (95% CI 0.32-1.57), but no such association was observed for long interspersed nuclear element-1 (LINE-1). We also found positive associations between DBP and methylation of the genes for toll-like receptor 2 (TLR2) and inducible nitric oxide synthase (iNOS), and a negative association between DBP and methylation of the gene for interferon-gamma (IFN-gamma). Associations between methylation and systolic blood pressure (SBP) were weaker than those between methylation and DBP. Bayesian mixed-effects structural equation model results were similar for both DBP and SBP models. %26lt;br%26gt;Conclusions The results of our study suggest that changes in DNA methylation of some pro-inflammatory genes and retrotransposable elements are related to small changes in BP.

• 出版日期2013-2