Repetitive element dna methylation and circulating endothelial and inflammation markers in the VA normative aging study

Andrea Baccarelli, Letizia Tarantini, Robert O. Wright, Valentina Bollati, Augusto A. Litonjua, Antonella Zanobetti, David Sparrow, Pantel Vokonas, Joel Schwartz

Research output: Contribution to journalArticlepeer-review

Abstract

Background: Lower blood DNA methylation has been associated with atherosclerosis and high cardiovascular risk. Mechanisms linking DNA hypomethylation to increased cardiovascular risk are still largely unknown. In a population of community-dwelling elderly individuals, we evaluated whether DNA methylation in LINE-1 repeti- tive element, heavily methylated sequences dispersed throughout the human genome, was associated with circulating Vascular cell Adhesion Molecule-1 (VcAM-1), Inter-cellular Adhesion Molecule-1 (IcAM-1) and c-reactive protein (cRp). Methods and results: We measured LINE-1 methylation by bisulfite pcR-pyrosequencing on 742 blood DNA samples from male participants in the Boston area Normative Aging study (mean age = 74.8 years). Mean serum VcAM-1 in- creased progressively in association with LINE-1 hypomethylation (from 975.2 to 1063.4 ng/ml in the highest vs. lowest methylation quintiles; p trend = 0.004). The association between VcAM-1 and LINE-1 hypomethylation was significant in individuals without ischemic heart disease or stroke (n = 480; p = 0.001), but not in those with prevalent disease (n = 262; p = 0.57). serum IcAM-1 and cRp were not associated with LINE-1 methylation (p trend = >0.25). All results were con- firmed by multivariable analyses adjusting for age, BMI, smoking, pack-years and ischemic heart disease/stroke. conclusions: LINE-1 element hypomethylation is associated with higher serum VCAM-1. Our data provide new insights into epigenetic events that may accompany the development of cardiovascular disease.

Original languageEnglish
Pages (from-to)222-228
Number of pages7
JournalEpigenetics
Volume5
Issue number3
DOIs
Publication statusPublished - Apr 1 2010

Keywords

  • Cardiovascular diseases
  • Cell adhesion molecules
  • Epidemiology
  • LINE-1
  • Risk factors
  • VCAM-1

ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research
  • Medicine(all)

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