β Fibrinogen Gene Polymorphisms Are Associated With Plasma Fibrinogen and Coronary Artery Disease in Patients With Myocardial Infarction

Abstract

Background Polymorphisms of the β 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 β 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 β fibrinogen gene, including five new polymorphisms identified by single-strand conformation polymorphism analysis, and one polymorphism in the 3′ flanking region of the α 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, β Hae III ( P <.0003) and β-854 ( P <.01), were independently associated with plasma fibrinogen. The significant association between β 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 β Bcl I ( P <.0003) and of other polymorphisms was positively associated with the severity of CAD. Conclusions Genetic variants of the β 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 β fibrinogen genotypes.