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Technical Briefs

Factor VII Gene Haplotypes and Risk of Ischemic Stroke

¹ Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Vienna, Vienna, Austria
² University Clinic of Neurology, Medical University of Vienna, Vienna, Austria
³ Department of Internal Medicine, Division of Angiology, Medical University of Vienna, Vienna, Austria
⁴ Hospital Barmherzige Brueder, Vienna, Austria

^* To whom correspondence should be addressed. E-mail: christine.mannhalter{at}meduniwien.ac.at.

Background: Coagulation factor VII (FVII) plays an important role in the activation of blood coagulation and clot formation. Recent studies have provided evidence for an association between common polymorphic markers in the FVII gene and plasma FVII concentrations. The 353R>Q sequence variation, and 3 common sequence variations in the promoter of the FVII gene--the 10-bp insertion/deletion at position -323 and the -401G>T and -402G>A sequence variations--are well-known determinants of circulating FVII concentrations.

Methods: To clarify the role of these sequence variations in the pathogenesis of ischemic stroke, we performed a case-control study with 242 patients with ischemic stroke before the age of 60 years and 239 healthy controls.

Results: The -323 insertion/deletion and the 353R>Q and -401G>T sequence variations were in strong linkage dysequilibrium, and the resulting haplotypes occurred with equal frequencies in patients and controls. The variant form of FVII (-402G>A) occurred only in combination with the common (wild-type) sequences at all other loci. This haplotype was more frequent in patients than in healthy controls (28% vs 22%). The difference in the prevalence of carriers of this haplotype among patients and controls was statistically significant (P = 0.03; odds ratio = 1.6; 95% confidence interval, 1.1-2.6).

Conclusion: According to our results, the FVII -402A allele seems to increase the risk of early ischemic cerebrovascular events, whereas the 353R>Q, G-401T, and -323ins/del sequence variations, which are in close linkage dysequilibrium, apparently do not influence the risk of stroke.