BETA-FIBRINOGEN GENE POLYMORPHISM (C-148-]T) IS ASSOCIATED WITH CAROTID ATHEROSCLEROSIS - RESULTS OF THE AUSTRIAN STROKE PREVENTION STUDY

Polymorphisms at the beta-fibrinogen locus have been shown to be assoc iated with plasma concentration of fibrinogen and coronary heart disea se. The effect of the genetic heterogeneity of fibrinogen on carotid a therosclerosis has not been determined so far. We examined the: influe nce of the C-148 --> T polymorphism on carotid disease in a large coho rt of middle-aged to elderly subjects without evidence of neuropsychia tric disease. This polymorphism is located close to the consensus sequ ence of the interleukin-6 element and may represent a functional seque nce variant. The genotype of 399 randomly selected, neurologically asy mptomatic individuals, aged 45 to 75 years, was determined by denaturi ng gradient gel electrophoresis. Carotid atherosclerosis was assessed by color-coded duplex scanning and was graded on a five-point scale ra nging from 0 (=normal) to 5 (=complete luminal obstruction). The C/C, C/T, and T/T genotypes were noted in 226 (56.6%), 148 (37.1%), and 25 (6.3%) individuals, respectively. The T/T genotype soup demonstrated h igher grades of carotid atherosclerosis than did the C/C and C/T genot ypes (P=.003). Logistic regression analysis created a model of indepen dent predictors of carotid atherosclerosis that included apolipoprotei n B (odds ratio [OR], 1.17/10 mg/dL), age (OR, 2.46/10 years), lifetim e tobacco consumption (OR, 1.03/1000 g), presence of the beta-fibrinog en promoter T/T genotype (OR, 6.17), plasma fibrinogen concentration ( OR, 1.05/10 mg/dL), and cardiac disease (OR, 1.80). These data suggest that the beta-fibrinogen promoter T/T148 genotype represents a geneti c risk factor for carotid atherosclerosis in tile middle-aged to elder ly.