Coronary artery disease and polymorphisms in a receptor mediating shear stress-dependent platelet activation

Background: Platelets play pivotal roles in coronary thrombosis, and antiplatelet therapies are widely used for coronary artery disease (CAD). However, the effects of genetic variation in platelets on CAD are poorly understood. We have assessed the association between CAD and polymorphisms in a platelet receptor for von Willebrand factor, the glycoprotein (GP) Ib/IX complex, which mediates shear stress-dependent platelet activation. Methods and Results: Genotypes of the α-chain of the receptor (GP Ibα, ¹⁴⁵Thr/Met) were determined in 91 patients with myocardial infarction (MI) or angina pectoris whose lesions were confirmed by coronary angiography as well as in 105 individuals from the general population with no history of angina or other heart diseases and normal resting ECGs. There was no homozygote for Met/Met in either the control or patient groups. The prevalence of the Thr/Met genotype (T/M) in all patients was not significantly different from that in the control group. However, the frequency of T/M was significantly higher in patients aged ≤60 years (31.8%) than in control subjects aged ≤60 years (16.0%; P<.05, odds ratio=2.5). An association was also demonstrated between CAD and the other polymorphism of GP Ibα, a variable number of tandem repeats of a 13-amino acid sequence, which is known to be linked to the ¹⁴⁵Thr/Met polymorphism. Them was an association between the frequency of the T/M genotype and the angiographic severity of CAD: 11.1% for Gensini score <40 versus 50.0% for Gensini score ≤40 (P=.0015). There was no difference in the distribution of GP Ibα genotypes between patients with MI and those with angina pectoris. Conclusions: This study suggests that the presence of the Met allele in GP Ibα is a risk factor for the prevalence and severity of CAD in individuals aged ≤60 years. The results need to be confirmed in a large-scale study of incident case subjects and matching control subjects.