Gender-specific associations of the fibrinogen B beta 448 polymorphism, fibrinogen levels, and acute cerebrovascular disease

Abstract

Fibrinogen is an independent risk factor for the development of stroke. Factors influencing circulating levels of fibrinogen include age, smoking, gender, and genetic factors. The aim of this study was to determine the relationship between a polymorphism at position 448 of the B beta fibrinogen gene, fibrinogen levels, gender, and the risk of stroke. Fibrinogen levels were determined in 305 patients with stroke, taken within 10 days of the acute event and 3 months later, and in 197 control subjects. Initial fibrinogen levels in patients (4.49 g/L) were significantly higher than at 3 months (3.85 g/L, P < .0001), consistent with resolution of the acute-phase response. At 3 months, levels were only significantly higher than for control subjects in the male patients (3.86 g/L versus 3.31 g/L, P < .0001). Fibrinogen levels were associated 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 (patients: 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 the development of cerebrovascular disease are different in males and females. In male patients, the increase in fibrinogen levels may be influenced by environmental factors, while in females there may be a functional difference in the fibrinogen molecule unrelated to fibrinogen levels.