© 1998 American Heart Association, Inc.
Original Contributions |
ß-Fibrinogen Gene Polymorphism (C148
T) Is Associated With Carotid Atherosclerosis
Results of the Austrian Stroke Prevention Study
From the Institute for Medical Biochemistry (H.S., P.B., G.M.K.) and the Departments of Neurology (R.S., K.N., S.H., B.R.) and Internal Medicine (M.S., V.W.), Karl-Franzens University, Graz, Austria.
Correspondence to Helena Schmidt, MD, Institute for Medical Biochemistry, Karl-Franzens University Graz, Harrachgasse 21, A-8010 Graz, Austria. E-mail helena.schmidt{at}kfunigraz.ac.at
Abstract—Polymorphisms at the
ß-fibrinogen locus have been shown to be associated with plasma
concentration of fibrinogen and coronary heart disease. The
effect of the genetic heterogeneity of fibrinogen on
carotid atherosclerosis has not been determined so far.
We examined the influence of the C148T polymorphism
on carotid disease in a large cohort of middle-aged to elderly subjects
without evidence of neuropsychiatric disease. This polymorphism is
located close to the consensus sequence of the interleukin-6 element
and may represent a functional sequence variant. The
genotype of 399 randomly selected, neurologically
asymptomatic individuals, aged 45 to 75 years, was
determined by denaturing gradient gel electrophoresis. Carotid
atherosclerosis was assessed by color-coded duplex
scanning and was graded on a five-point scale ranging 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 group
demonstrated higher grades of carotid atherosclerosis
than did the C/C and C/T
genotypes (P=.003). Logistic
regression analysis created a model of independent predictors
of carotid atherosclerosis that included apolipoprotein
B (odds ratio [OR], 1.17/10 mg/dL), age (OR, 2.46/10 years), lifetime
tobacco consumption (OR, 1.03/1000 g), presence of the ß-fibrinogen
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 ß-fibrinogen promoter
T/T148 genotype represents a
genetic risk factor for carotid atherosclerosis in the
middle-aged to elderly.
Key Words: fibrinogen • genetics • atherosclerosis • carotid arteries
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