Factor VII Gene Haplotypes and Risk of Ischemic Stroke (Technical Briefs‪)‬

Coagulation factor VII (FVII) is a vitamin K-dependent protease that plays a key role in the initiation of the activation of the blood coagulation cascade. The factor VIIa-tissue factor complex initiates coagulation by limited proteolysis of factors IX and X. Increased FVII coagulant activity has been associated with cardiovascular disease (1-3), carotid intima-media thickness increase (4), and cerebrovascular disease (5). Because of controversial results in other studies (6, 7), the role of increased FVII concentrations in vascular disease remains unclear. It has been shown that FVII concentrations are influenced not only by exogenous factors, including age, sex, diet, and hormonal status (8), but also by genetic factors. Sequence variations in the FVII gene account for approximately one third of the variations in plasma FVII concentrations (9). The FVII gene is located on chromosome 13 and contains several polymorphic sites. Among them are the 353RQ sequence variation and 3 common variants in the promoter of the FVII gene-the 10-bp insertion/ deletion at position -323, the -401GT sequence variation, and the -402GA sequence variation-which are well-known determinants of circulating FVII concentrations. The sequence variant at nucleotide (nt) -402 has been reported to contribute to increased FVII concentrations (10), whereas the variants at nt -401 and -323 and the 353RQ variant have been associated with decreased factor VII concentrations (9-11). The role of these sequence variations in the development of vascular disease is still controversial.