title: Association between blood pressure and DNA methylation of retrotransposons and pro-inflammatory genes.
abstract: 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.
  
  
  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' 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.
  
  
  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-γ (IFN-γ). 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.
  
  
  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.
authors.affiliation: Department of Environmental Health, Harvard School of Public Health, Boston MA 02215, USA. salexeeff@fas.harvard.edu
authors.forename: Stacey E
authors.initials: SE
authors.lastname: Alexeeff
authors.forename: Andrea A
authors.initials: AA
authors.lastname: Baccarelli
authors.forename: Jaana
authors.initials: J
authors.lastname: Halonen
authors.forename: Brent A
authors.initials: BA
authors.lastname: Coull
authors.forename: Robert O
authors.initials: RO
authors.lastname: Wright
authors.forename: Letizia
authors.initials: L
authors.lastname: Tarantini
authors.forename: Valentina
authors.initials: V
authors.lastname: Bollati
authors.forename: David
authors.initials: D
authors.lastname: Sparrow
authors.forename: Pantel
authors.initials: P
authors.lastname: Vokonas
authors.forename: Joel
authors.initials: J
authors.lastname: Schwartz
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000235:genetics; D001483:Base Sequence; D001499:Bayes Theorem; D015415:Biomarkers / Q000378:metabolism; D001794:Blood Pressure / Q000235:genetics* / Q000502:physiology; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D005260:Female; D015870:Gene Expression; D006801:Humans; D007249:Inflammation / Q000235:genetics*; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D052247:Nitric Oxide Synthase Type II / Q000235:genetics; D016133:Polymerase Chain Reaction; D018626:Retroelements / Q000235:genetics*
chemical_list: D015415:Biomarkers; D018626:Retroelements; D052247:Nitric Oxide Synthase Type II