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(Stroke. 2002;33:2762.)
© 2002 American Heart Association, Inc.

Original Contributions

Cryptogenic Stroke in Relation to Genetic Variation in Clotting Factors and Other Genetic Polymorphisms Among Young Men and Women

Harland Austin, DSc; Marc I. Chimowitz, MBChB; Holly A. Hill, MD, PhD; Seemant Chaturvedi, MD; Lawrence R. Wechsler, MD; Robert J. Wityk, MD; Elizabeth Walz, MD; Janet L. Wilterdink, MD; Bruce Coull, MD; Cathy A. Sila, MD; Panos Mitsias, MD; Bruce Evatt, MD W. Craig Hooper, PhD for the Genetics and Stroke in the Young Study Group

From the Division of AIDS, STD, and TB Laboratory Research, National Center for Infectious Diseases, Centers for Disease Control and Prevention, Public Health Service, US Department of Health and Human Services, Atlanta, Ga (H.A., B.E., W.C.H.); Department of Epidemiology, School of Public Health (H.A., H.A.H.) and Department of Neurology (M.I.C.), Emory University School of Medicine, Atlanta, GA; Department of Neurology, Wayne State University School of Medicine, Detroit, Mich (S.C.); Stroke Institute, University of Pittsburgh Medical Center, Pittsburgh, Pa (L.R.W.); Johns Hopkins University School of Medicine, Baltimore, Md (R.J.W.); Department of Neurology, Ohio State University Medical Center, Columbus (E.W.); Department of Neurology, Rhode Island Hospital, Providence (J.L.W.); Department of Neurology, University of Arizona Health Sciences Center, Tucson (B.C.); Cleveland Clinic Foundation, Cleveland, Ohio (C.A.S.); and Department of Neurology, Henry Ford Hospital, Detroit, Mich (P.M.).

Correspondence to Harland Austin, Emory University, 1518 Clifton Rd NE, Atlanta, GA 30322. E-mail haustin{at}sph.emory.edu

Background and Purpose— The purpose of the present study was to compare the prevalences of genetic polymorphisms in persons with cryptogenic stroke with those among stroke patients with evidence of large-artery occlusive disease or an unequivocal cardioembolic source (noncryptogenic stroke).

Methods— We compared the prevalences of genetic polymorphisms thought to be related to thrombi formation in young stroke patients with evidence of large-artery occlusive disease or an unequivocal cardioembolic source (noncryptogenic stroke; controls; n=79) with those in young stroke patients without such sources (cryptogenic stroke; cases; n=67). Common variations in the genes encoding factor V, prothrombin, angiotensin I–converting enzyme, 5,10-methylenetetrahydrofolate reductase, endothelial cell nitric oxide synthase, tissue plasminogen activator, plasminogen activator inhibitor–1, and fibrinogen were evaluated. We also compared the allele prevalence of these genes among all stroke patients with those among a large pool of historical controls assayed for these genes.

Results— None of these genetic polymorphisms was statistically significantly related to cryptogenic stroke. With respect to a comparison of all ischemic stroke with historical controls, only the prevalence of tissue plasminogen activator D allele among stroke subjects was statistically significantly higher than that of the historical controls (P=0.0014).

Conclusions— These findings generally do not support the hypothesis that genes associated with a prothrombotic state are risk factors among a subgroup of young people with stroke of undetermined cause. Except for the D tissue plasminogen activator allele, the findings also indicated that these genetic factors are unrelated, or only weakly related, to all ischemic stroke.

Editorial Comment

Robert A. Hegele, MD, FRCPC, FACP, Guest Editor

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