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(Circulation. 1996;93:440-449.)
© 1996 American Heart Association, Inc.
Articles |
ß Fibrinogen Gene Polymorphisms Are Associated With Plasma Fibrinogen and Coronary Artery Disease in Patients With Myocardial Infarction
The ECTIM Study
From INSERM SC7, Paris, France (I.B., O.P., F.C.); INSERM U258, Paris, France (V.N., P.-Y.S.); the MONICA projects: Belfast, UK (A.E.), Strasbourg, France (D.A.), Lille, France (G.L.), and Toulouse, France (J.-P.C.); Hematology Department, Paris VI University, Paris, France (L.B.); and Department of Medicine, UCL Medical School, London, UK (F.G.).
Correspondence to Dr François Cambien, INSERM SC7, 17 rue du Fer à Moulin, 75005 Paris, France.
Background Polymorphisms of the ß fibrinogen gene have been shown to affect plasma fibrinogen levels and the risk of peripheral arterial disease. We now present the results of a detailed analysis of the ß fibrinogen gene in relation to plasma fibrinogen and to the severity of coronary artery disease (CAD) in patients with myocardial infarction (MI) in the ECTIM Study.
Methods and Results Ten polymorphisms of the ß
fibrinogen gene, including five new polymorphisms identified by
single-strand conformation polymorphism analysis, and
one polymorphism in the 3' flanking region of the 
fibrinogen
gene were investigated in 565 patients with MI and 668 control
subjects. The polymorphisms were in tight linkage disequilibrium
and the genotype frequencies were similar in patients with MI
and control subjects. In the multivariate
analysis, only two polymorphisms, ß Hae III
(P<.0003) and ß-854 (P<.01), were
independently associated with plasma fibrinogen. The significant
association between ß fibrinogen polymorphisms and plasma
fibrinogen was present in smokers but not in nonsmokers. In French
MI patients, the number of coronary arteries with >50%
stenosis was estimated by angiography and used as a criterion
for severity of CAD. Presence of the less frequent allele of the
ß Bcl I (P<.0003) and of other
polymorphisms was positively associated with the severity of CAD.
Conclusions Genetic variants of the ß fibrinogen gene are associated with an increased plasma level of fibrinogen, especially in smokers. The association with CAD appears to be the consequence of an increased risk of MI in subjects with severe CAD who carry the predisposing ß fibrinogen genotypes.
Key Words: genetics • fibrinogen • coronary disease • myocardial infarction
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