Title
455G/A polymorphism of the beta-fibrinogen gene is associated with the progression of coronary atherosclerosis in symptomatic men: Proposed role for an acute-phase reaction pattern of fibrinogen
Author
de Maat, M.P.M.
Kastelein, J.J.P.
Jukema, J.W.
Zwinderman, A.H.
Jansen, H.
Groenemeier, B.
Bruschke, A.V.G.
Kluft, C.
Gaubius instituut TNO
Publication year
1998
Abstract
Increased plasma fibrinogen levels have been identified as a risk indicator for myocardial infarction, stroke, and thrombosis. Both environmental and genetic factors make an important contribution to plasma fibrinogen levels in humans. In the present study we evaluated, in patients with serum cholesterol levels between 4 and 8 mmol/L, the relation of plasma levels and polymorphisms of fibrinogen with coronary artery disease (CAD), cross-sectionally at baseline and after a 2-year follow-up period in which they received either a placebo or pravastatin. Higher plasma fibrinogen levels (3.9 g/L) were observed at baseline in patients with the -455AA genotype than in patients with the -455GA (3.2 g/L) and -455GG (3.1 g/L) genotypes of the -455G/A fibrinogen β gene polymorphism (P < .05). Plasma levels of fibrinogen were not related to the baseline angiographic variables (mean segment diameter [MSD] and minimum obstruction diameter [MOD]), nor to the quantitative changes in these angiographic variables. However, in the placebo group, patients with the - 455AA genotype had more progression of CAD, expressed by a significantly greater decrease of the MSD and MOD, after the 2-year follow-up period than patients with the other genotypes. The - 455G/A polymorphism was related to the progression of CAD, and pravastatin therapy seemed to offset this deleterious effect. We hypothesized that the - 455A allele may promote a stronger acute-phase response in fibrinogen and that the resulting higher fibrinogen levels may form the pathogenetic basis for the stronger progression of coronary atherosclerosis. Experiments to verify this hypothesis are being proposed and advocated, in view of the possibility of identifying a genetic marker that can recognize a subgroup of patients with an increased risk who may benefit from early treatment with lipid-lowering or anticoagulant drugs.
Subject
Biology
Cardiovascular diseases
Fibrinogen
Genetics
Aged
Coronary Angiography
Coronary Arteriosclerosis
Disease Progression
Double-Blind Method
Fibrinogen
Genotype
Humans
Male
Middle Aged
Polymorphism, Genetic
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DOI
https://doi.org/10.1161/01.atv.18.2.265
TNO identifier
234510
ISSN
1079-5642
Source
Arteriosclerosis, Thrombosis, and Vascular Biology, 18 (2), 265-271
Document type
article