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(Stroke. 2001;32:2580.)
© 2001 American Heart Association, Inc.

Original Contributions

Polymorphisms of Coagulation Factor XIII Subunit A and Risk of Nonfatal Hemorrhagic Stroke in Young White Women

Alexander P. Reiner, MD; Stephen M. Schwartz, PhD; Michele B. Frank, MD; W.T. Longstreth, Jr, MD, MPH; Lucia A. Hindorff, BA; Gayle Teramura, BS; Frits R. Rosendaal, MD; Lakshmi K. Gaur, PhD; Bruce M. Psaty, MD, PhD David S. Siscovick, MD, MPH

From the Departments of Medicine (A.P.R, M.B.F., W.T.L., G.T., B.M.P., D.S.S.), Epidemiology (A.P.R., S.M.S., W.T.L., L.A.H., B.M.P., D.S.S.), Neurology (W.T.L.), Health Services (B.M.P.), Microbiology (L.K.G.), and Cardiovascular Health Research Unit (W.T.L., S.MS, B.M.P., D.S.S.), University of Washington, Seattle; Fred Hutchinson Cancer Research Center (S.M.S.), Seattle, Wash; and the Hemostasis and Thrombosis Research Center and Department of Clinical Epidemiology (F.R.R.), Leiden University Medical Center, Leiden, the Netherlands.

Correspondence to Alexander P. Reiner, MD, 7546 24th Ave NE, Seattle, WA 98115. E-mail apreiner{at}u.washington.edu

Background and Purpose—— Although family studies have suggested a genetic influence on hemorrhagic stroke, the underlying genetic risk factors remain poorly defined. Coagulation factor XIII, which is involved in hemostasis, fibrinolysis, vascular remodeling, and tissue repair, represents a candidate gene for hemorrhagic stroke. We assessed the potential role of 3 factor XIII subunit A coding–sequence polymorphisms, along with a promoter polymorphism of plasminogen activator inhibitor-1 (PAI-1, which is also involved in fibrin stabilization and vascular remodeling), in young white women with hemorrhagic stroke.

Methods—— Genotype analysis for factor XIII subunit A Val34Leu, Tyr204Phe, and Pro564Leu and for PAI-1 -675 4G/5G was performed in a population-based case-control study of 42 white women aged <45 years with nonfatal hemorrhagic stroke and 345 demographically similar control subjects.

Results—— Compared with the respective homozygous wild-type genotypes, the Tyr204/Phe204 genotypes (age-adjusted odds ratio [OR] 2.9, 95% 95% CI 1.1 to 7.5) and the Leu564/Leu564 genotype (OR 4.3, 95% CI 1.4 to 13.7) were each associated with an increased risk of nonfatal hemorrhagic stroke. The risk estimate associated with the Phe204 variant was highest in women with subarachnoid hemorrhage and in nonsmokers, whereas the risk estimate of the Leu564/Leu564 genotype was highest in women with intracerebral hemorrhage and in smokers. Women who carried either the Phe204 allele or the Leu564/Leu564 genotype in combination with the PAI-1 5G/5G genotype had a nearly 20-fold increased risk of hemorrhagic stroke (OR 18.9, 95% CI 3.8 to 95.1).

Conclusions—— Our findings suggest that the Phe204 and Leu564 variants of coagulation factor XIII may be markers for genetic susceptibility to hemorrhagic stroke in women aged <45 years.

Editorial Comment

Jacques R. Leclerc, MD, FRCP(C), Guest Editor

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