Genetic variation in the promoter region of the ??-fibrinogen gene is associated with ischemic stroke in a Japanese population

Abstract

Evidence suggests that an allelic variation in the β fibrinogen gene may confer an increased risk of coronary artery disease and stroke. The role of the β fibrinogen gene polymorphism and fibrinogen levels in ischemic stroke has not been determined in Japanese, who are more prone to stroke than to coronary artery disease compared with Caucasians. We investigated the associations between ischemic stroke, plasma fibrinogen level, and a HaeIII restriction fragment length polymorphism (G/A^-455) located at −455 bp from the start of transcription of the β fibrinogen gene in 85 hypertensive patients with ischemic stroke (stroke group), 85 hypertensive patients without ischemic stroke (nonstroke group) and in 84 normotensive subjects matched for age, sex, and smoking status recruited at an annual health examination (normotensive group). The frequency of non-cutting allele (designated A^-455 allele) in the control group was 0.07 [95%CI: 0.03–0.11]; this value was significantly lower than that previously reported in Caucasians (0.19–0.26). The A^-455 allele frequency of the nonstroke group and stroke group were 0.08 [95% CI: 0.04–0.12] and 0.15 [95% CI: 0.10–0.21]. A^-455 allele frequency of the stroke group was significantly higher than that of the control group (x² = 5.63, P = 0.018) and the nonstroke group (x² = 4.00, P = 0.043). The mean × SD fibrinogen level was significantly higher in the stroke group than that in the normotensive group (277 × 64 mg/dl versus 257 × 52 mg/dl, P < 0.03), but that of the nonstroke group was not significantly different compared with both normotensive and stroke groups. In conclusion, the positive association between the fibrinogen genotype G/A^-455 and ischemic stroke in hypertensive patients was independent of other risk factors. These results suggest that fibrinogen A^-455 allele may be an independent risk factor for ischemic stroke in the Japanese population. Blood Coag Fibrinol 9:373–379 × 1998 Lippincott-Raven Publishers.