This Article Full Text Full Text (PDF) All Versions of this Article: 40/2/363    most recent STROKEAHA.108.521328v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Luke, M. M. Articles by Psaty, B. M. Search for Related Content PubMed PubMed Citation Articles by Luke, M. M. Articles by Psaty, B. M. Related Collections Risk Factors Genetics of Stroke Epidemiology Genetics of cardiovascular disease

(Stroke. 2009;40:363.)
© 2009 American Heart Association, Inc.

Original Contributions

Gene Variants Associated With Ischemic Stroke

The Cardiovascular Health Study

May M. Luke, MBA, PhD; Ellen S. O'Meara, PhD; Charles M. Rowland, MS; Dov Shiffman, PhD; Lance A. Bare, PhD; Andre R. Arellano, BS; W.T. Longstreth, Jr, MD, MPH; Thomas Lumley, PhD; Kenneth Rice, PhD; Russell P. Tracy, PhD; James J. Devlin, PhD Bruce M. Psaty, MD, PhD

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.

Correspondence to May M. Luke, MBA, PhD, Celera, 1401 Harbor Bay Parkway, Alameda, CA 94502. 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.

Key Words: brain infarction • cerebrovascular accident • epidemiology • genetics • prevention • risk factors

This article has been cited by other articles:

				J. Kim, Y. K. Chae, M. A. Ikram, S. Seshadri, J. C. Bis, and the Cohorts in Heart and Aging Research Consortium Genomewide Association Studies of Stroke N. Engl. J. Med., August 13, 2009; 361(7): 722 - 722. [Full Text] [PDF]

				J. M. A. Delou, A. G. Lopes, and M. A.M. Capella Unveiling the Role of Multidrug Resistance Proteins in Hypertension Hypertension, August 1, 2009; 54(2): 210 - 216. [Full Text] [PDF]