Polymorphisms of coagulation factor XIII subunit A and risk of nonfatal hemorrhagic stroke in young white women

Background and Purpose-Although family studies have suggested a genetic inf luence on hemorrhagic stroke, the underlying genetic risk factors remain po orly defined. Coagulation factor XIII, which is involved in hemostasis, fib rinolysis, vascular remodeling, and tissue repair, represents a candidate g ene for hemorrhagic stroke. We assessed the potential role of 3 factor XIII subunit A coding-sequence polymorphisms, along with a promoter polymorphis m of plasminogen activator inhibitor-1 (PAI-1, which is also involved in fi brin stabilization and vascular remodeling), in young white women with hemo rrhagic stroke. Methods-Genotype analysis for factor XIII subunit A Val34Leu, Tyr204Phe, an d Pro564Leu and for PAI-1 -675 4G/5G was performed in a population-based ca se-control study of 42 white women aged < 45 years with nonfatal hemorrhagi c stroke and 345 demographically similar control subjects. Results-Compared with the respective homozygous wild-type genotypes, the Ty r204/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 subar achnoid hemorrhage and in nonsmokers, whereas the risk estimate of the Leu5 64/Leu564 genotype was highest in women with intracerebral hemorrhage and i n smokers. Women who carried either the Phe204 allele or the Leu564/Leu564 genotype in combination with the PAI-I 5G/5G genotype had a nearly 20-fold increased risk of hemorrhagic stroke (OR 18.9, 95% Cl 3.8 to 95.1). Conclus ions-Our findings suggest that the Phe204 and Leu564 variants of coagulatio n factor XIII may be markers, for genetic susceptibility to hemorrhagic str oke in women aged < 45 years.