on November 20, 2008
Published online before print November 20, 2008, doi: 10.1161/STROKEAHA.108.521328
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Submitted on March 25, 2008
From Celera (M.M.L., C.M.R., D.S., L.A.B., A.R.A., J.J.D.), Alameda, Calif; the Department of Biostatistics (E.S.O., T.L., K.R.), School of Public Health and Community Medicine, University of Washington, Seattle, Wash; the Cardiovascular Health Research Unit (W.T.L., T.L., B.M.P.), the Department of Neurology (W.T.L.), and the Departments of Medicine, Epidemiology, and Health Services (B.M.P.), University of Washington, Seattle, Wash; the Departments of Pathology and Biochemistry (R.P.T.), College of Medicine, University of Vermont, Burlington, Vt; and the Center for Health Studies (B.M.P.), Group Health, Seattle, Wash. * To whom correspondence should be addressed. E-mail: may.luke{at}celera.com.
Background and Purpose—The purpose of this study was to determine whether 74 single nucleotide polymorphisms (SNPs), which had been associated with coronary heart disease, are associated with incident ischemic stroke. Methods—Based on antecedent studies of coronary heart disease, we prespecified the risk allele for each of the 74 SNPs. We used Cox proportional hazards models that adjusted for traditional risk factors to estimate the associations of these SNPs with incident ischemic stroke during 14 years of follow-up in a population-based study of older adults: the Cardiovascular Health Study (CHS). Results—In white CHS participants, the prespecified risk alleles of 7 of the 74 SNPs (in HPS1, ITGAE, ABCG2, MYH15, FSTL4, CALM1, and BAT2) were nominally associated with increased risk of stroke (one-sided P<0.05, false discovery rate=0.42). In black participants, the prespecified risk alleles of 5 SNPs (in KRT4, LY6G5B, EDG1, DMXL2, and ABCG2) were nominally associated with stroke (one-sided P<0.05, false discovery rate=0.55). The Val12Met SNP in ABCG2 was associated with stroke in both white (hazard ratio, 1.46; 90% CI, 1.05 to 2.03) and black (hazard ratio, 3.59; 90% CI, 1.11 to 11.6) participants of CHS. Kaplan-Meier estimates of the 10-year cumulative incidence of stroke were greater among Val allele homozygotes than among Met allele carriers in both white (10% versus 6%) and black (12% versus 3%) participants of CHS. Conclusions—The Val12Met SNP in ABCG2 (encoding a transporter of sterols and xenobiotics) was associated with incident ischemic stroke in white and black participants of CHS.
Accepted on June 19, 2008
Gene Variants Associated With Ischemic Stroke. The Cardiovascular Health Study
May M. Luke MBA, PhD*;
Key words: brain infarction • cerebrovascular accident • epidemiology • genetics • prevention • risk factors
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