Association of the platelet glycoprotein IIb HPA-3 polymorphism with survival after acute ischemic stroke

Abstract

Background and Purpose - The role of polymorphisms of the platelet glycoprotein (GP) IIb/IIIa receptor in the development of cardiovascular disease has been the subject of intensive research. The aim of this study was to determine the association of the HPA-3 polymorphism of platelet GPIIb with ischemic stroke and subsequent survival and to identify possible interactions of HPA-3 with classic risk factors. Methods - HPA-3 genotype was determined by restriction fragment length polymorphism in 515 patients with ischemic stroke and 423 healthy, age-matched control subjects. Results - There was no significant difference in the genotype distribution of patients and controls, nor was there any difference when patients were subclassified into small- and large-vessel disease. The genotype distribution of the 231 patients subsequently dying during 2.8 years of follow-up (aa=45.0%, ab=46.8%, bb=8.2%) was significantly different from that of those still alive (aa=37.0%, ab=48.2%, bb=14.8%) (P=0.03). In a Cox regression model, the relative risks for poststroke mortality in patients of aa and ab genotype compared with those of bb genotype were 2.42 (95% CI, 1.24 to 4.71) and 2.13 (95% CI, 1.09 to 4.17), respectively, after we accounted for confounding factors. In addition, significant interactions of HPA-3 with the P1(A) polymorphism of GPIIIa (P=0.002) and with fibrinogen (P=0.01) were identified in relation to mortality. Conclusions - HPA-3 is related to poststroke mortality, and the significant interaction of HPA-3 with Pl(A) and fibrinogen suggests that it may in some way influence the interaction of GpIIb/IIIa with fibrinogen, particularly in the presence of high fibrinogen.