title: Ischemic heart disease and stroke in relation to blood DNA methylation.
abstract: BACKGROUND
  Epigenetic features such as DNA hypomethylation have been associated with conditions related to cardiovascular risk. We evaluated whether lower blood DNA methylation in heavily methylated repetitive sequences predicts the risk of ischemic heart disease and stroke.
  
  
  METHODS
  We quantified blood DNA methylation of Long Interspersed Nucleotide Element-1 (LINE-1) repetitive elements through PCR-pyrosequencing in 712 elderly individuals from the Boston-area Normative Aging Study. We estimated risk-factor adjusted relative risks (RRs) for ischemic heart disease and stroke at baseline (242 prevalent cases), and during follow-up (44 new cases; median follow-up, 63 months), as well as subsequent mortality from ischemic heart disease (86 deaths; median follow-up, 75 months).
  
  
  RESULTS
  Blood LINE-1 hypomethylation was associated with baseline ischemic heart disease (RR = 2.1 [95% confidence interval = 1.2-4.0] for lowest vs. highest methylation quartile) and for stroke (2.5 [0.9-7.5]). Among participants free of baseline disease, individuals with methylation below the median also had higher risk of developing ischemic heart disease (4.0 [1.8-8.9]) or stroke (5.7 [0.8-39.5]). In the entire cohort, persons with methylation below the median had higher mortality from ischemic heart disease (3.3 [1.3-8.4]) and stroke (2.8 [0.6-14.3]). Total mortality was also increased (2.0 [1.2-3.3]). These results were confirmed in additional regression models using LINE-1 methylation as a continuous variable.
  
  
  CONCLUSIONS
  Subjects with prevalent IHD and stroke exhibited lower LINE-1 methylation. In longitudinal analyses, persons with lower LINE-1 methylation were at higher risk for incident ischemic heart disease and stroke, and for total mortality.
authors.affiliation: Center of Molecular and Genetic Epidemiology, Università degli Studi di Milano & IRCCS Ca', Granda Policlinico Maggiore Hospital Foundation, Milan, Italy. abaccare@hsph.harvard.edu
authors.forename: Andrea
authors.initials: A
authors.lastname: Baccarelli
authors.forename: Robert
authors.initials: R
authors.lastname: Wright
authors.forename: Valentina
authors.initials: V
authors.lastname: Bollati
authors.forename: Augusto
authors.initials: A
authors.lastname: Litonjua
authors.forename: Antonella
authors.initials: A
authors.lastname: Zanobetti
authors.forename: Letizia
authors.initials: L
authors.lastname: Tarantini
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; D001900:Boston / Q000453:epidemiology; D003430:Cross-Sectional Studies; D019175:DNA Methylation; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D015994:Incidence; D020084:Long Interspersed Nucleotide Elements / Q000235:genetics*; D008297:Male; D017202:Myocardial Ischemia / Q000235:genetics* / Q000401:mortality; D016133:Polymerase Chain Reaction; D020521:Stroke / Q000235:genetics* / Q000401:mortality
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