Role of Kozak sequence polymorphism of platelet glycoprotein Ibα as a risk factor for coronary artery disease and catheter interventions

OBJECTIVES We sought to determine the role of the −5T/C polymorphism of the platelet glycoprotein (GP) Ibα as a potential risk factor for coronary artery disease (CAD) and adverse events complicating a coronary catheter intervention. BACKGROUND The platelet GP Ib-IX-V receptor complex plays a crucial role in arterial thrombus formation. The −5T/C polymorphism of GP Ibα is associated with increased receptor density. METHODS We genotyped 1,000 patients with angiographically confirmed CAD, as well as 1,000 age- and gender-matched control subjects, for this polymorphism by polymerase chain reaction/restriction fragment length polymorphism. Among the patients with CAD, 269 underwent percutaneous transluminal coronary angioplasty (PTCA), 103 underwent directional coronary atherectomy and 278 underwent stenting. This intervention group was followed for a 30-day composite end point of target vessel revascularization, myocardial infarction or death. RESULTS Carriers of the −5C allele were significantly over-represented in the group of patients developing acute coronary syndromes (relative risk [RR] 1.43, 95% confidence interval [CI] 1.05 to 1.95, P = 0.02). The −5C allele furthermore predicted an increased risk for developing complications after PTCA (RR 3.75, 95% CI 1.15 to 12.27, P = 0.029). CONCLUSIONS The −5C allele of the GP Ibα Kozak polymorphism may represent a risk factor in clinical conditions in which thrombosis plays an important role, such as in acute coronary syndromes and in complications after PTCA.