Association of the Platelet Pl A Polymorphism of Glycoprotein IIb/IIIa and the Fibrinogen Bβ 448 Polymorphism With Myocardial Infarction and Extent of Coronary Artery Disease

Abstract

Background Platelets and fibrinogen play an integral role in the development of thrombosis and are implicated in the process of atherosclerosis. The fibrinogen Bβ 448 polymorphism and the Pl A polymorphism of platelet glycoprotein IIIa are reported to be independently associated with coronary artery disease. The aim of this study was to determine the association of the fibrinogen Bβ 448 and the platelet glycoprotein IIIa Pl A polymorphisms in relation to extent of coronary atheroma as characterized by angiography and a past history of myocardial infarction (MI) as assessed by World Health Organization criteria. Methods and Results Caucasian patients (n=405) admitted for routine angiography for investigation of chest pain or suspected coronary artery disease were recruited. Caucasian control subjects (n=216) were recruited from local Family Health Services Authority general practice registers. Fibrinogen levels were higher ( P =.04) in male patients (3.24 g/L; CI, 3.14 to 3.35) than male control subjects (3.06 g/L; CI, 2.91 to 3.21). There was a trend toward a difference ( P =.06) in fibrinogen genotype distributions between female patients (1/1=93, 1/2=31, and 2/2=1) and female control subjects (1/1=67, 1/2=34, and 2/2=5). In logistic regression models the Pl A2 genotype was associated with MI (odds ratio, 1.66; CI, 1.15 to 2.39; P =.007) and stenosis of more than one vessel (odds ratio, 1.5; CI, 1.01 to 2.26; P =.04). In men suffering an MI before the age of 47 years there was a 50% incidence of the Pl A2 allele ( P =.05), and in these subjects there was evidence of an interaction with cholesterol ( P =.04). Conclusions We found evidence of an association of the Pl A2 polymorphism in MI and multiple-vessel stenosis. The association with MI was strongest in young men, in whom there was also evidence of an interaction with cholesterol.