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

Background and Purpose-The role of polymorphisms of the platelet glycoprote in (GP) IIb/IIIa receptor in the development of cardiovascular disease has been the subject of intensive research. The aim of this study was to determ ine the association of the HPA-3 polymorphism of platelet GPIIb with ischem ic 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 polymo rphism in 515 patients with ischemic stroke and 423 healthy, age-matched co ntrol subjects. Results-There was no significant difference in the: genotype distribution o f patients and controls, nor was there any difference when patients were su bclassified into small- and large-vessel disease. The genotype distribution of the 231 patients subsequently dying during 2.8 years of follow-up (aa=4 5.0%, ab=46.8 %, bb=8.2%) was significantly different from that of those st ill alive (aa=37.0%, ab=48.2%, bb=14.8%) (P=0.03). In a Cox regression mode l, the relative risks for poststroke mortality in patients of aa and nb gen otype compared with those of bb genotype were 2.42 (95% CI, 1.24 to 4.71) a nd 2.13 (95% CI, 1.09 to 4.17), respectively, after we accounted for confou nding factors. In addition. significant interactions of HPA-3 with the PIA polymorphism of GPIIIa (P=0.002) and with fibrinogen (P=0.01) were identifi ed in relation to mortality. Conclusions-HPA-3 is related to poststroke mortality, and the significant i nteraction of HPA-3 with P1(A) and fibrinogen suggests that it may in some way influence the interaction of GPIIb/IIIa with fibrinogen, particularly i n the presence of high fibrinogen.