GENDER-SPECIFIC ASSOCIATIONS OF THE FIBRINOGEN B-BETA-448 POLYMORPHISM, FIBRINOGEN LEVELS, AND ACUTE CEREBROVASCULAR-DISEASE

Fibrinogen is an independent risk factor for the development of stroke . Factors influencing circulating levels of fibrinogen include age, sm oking, gender, and genetic factors. The aim of this study was to deter mine the relationship between a polymorphism at position 448 of the B beta fibrinogen gene, fibrinogen levels, gender, and the risk of strok e. Fibrinogen levels were determined in 305 patients with stroke, take n within 10 days of the acute event and 3 months later, and in 197 con trol subjects. Initial fibrinogen levels in patients (4.49 g/L) were s ignificantly higher than at 3 months (3.85 g/L, P<.0001), consistent w ith resolution of the acute-phase response. At 3 months, levels were o nly significantly higher than for control subjects in the male patient s (3.86 g/L versus 3.31 g/L, P<.0001). Fibrinogen levels were associat ed with B beta 448 genotype in male patients at 3 months (1/1=3.62 g/L , 1/2+2/2=4.27 g/L, P=.01). There was a significant difference in the genotype distribution in female patients and control subjects (patient s: 1/1=95, 1/2=34, 2/2=6; control subjects: 1/1=61, 1/2=50, 2/2=3, P=. 008). These data suggest that the mechanisms linking fibrinogen and th e development of cerebrovascular disease are different in males and fe males. In male patients, the increase in fibrinogen levels may be infl uenced by environmental factors, while in females there may be a funct ional difference in the fibrinogen molecule unrelated to fibrinogen le vels.