GENETIC-VARIATION IN THE PROMOTER REGION OF THE BETA-FIBRINOGEN GENE IS ASSOCIATED WITH ISCHEMIC STROKE IN A JAPANESE POPULATION

Evidence suggests that an allelic variation in the beta fibrinogen gen e may confer an increased risk of coronary artery disease and stroke. The role of the beta fibrinogen gene polymorphism and fibrinogen level s in ischemic stroke has not been determined in Japanese, who are more prone to stroke than to coronary artery disease compared with Caucasi ans. We investigated the associations between ischemic stroke, plasma fibrinogen level, and a HaeIII restriction fragment length polymorphis m (G/A(-455)) located at -455 bp from the start of transcription of th e beta fibrinogen gene in 85 hypertensive patients with ischemic strok e (stroke group), 85 hypertensive patients without ischemic stroke (no nstroke group) and in 84 normotensive subjects matched for age, sex, a nd smoking status recruited at an annual health examination (normotens ive group). The frequency of non-cutting allele (designated A(-455) al lele) in the control group was 0.07 [95% CI: 0.03-0.11]; this value wa s significantly lower than that previously reported in Caucasians (0.1 9-0.26). The A(-455) allele frequency of the nonstroke group and strok e 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 th an that of the control group (chi(2) = 5.63, P = 0.018) and the nonstr oke group (chi(2) = 4.00, P = 0.043). The mean +/- SD fibrinogen level was significantly higher in the stroke group than that in the normote nsive group (277 +/- 64 mg/dl versus 257 +/- 52 mg/dl, P < 0.03), but that of the nonstroke group was not significantly different compared w ith both normotensive and stroke groups. In conclusion, the positive a ssociation between the fibrinogen genotype G/A(-455) and ischemic stro ke in hypertensive patients was independent of other risk factors. The se results suggest that fibrinogen A(-455) allele may be an independen t risk factor for ischemic stroke in the Japanese population. Blood Co ag Fibrinol 9:373-379 (C) 1998 Lippincott-Raven Publishers.