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 (aaϭ45.0%, abϭ46.8%, bbϭ8.2%) was significantly different from that of those still alive (aaϭ37.0%, abϭ48.2%, bbϭ14.8%) (Pϭ0.03). 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 Pl A polymorphism of GPIIIa (Pϭ0.002) and with fibrinogen (Pϭ0.01) 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.

Platelet glycoprotein IIb/IIIa (HPA-1 and HPA-3) polymorphisms in patients with hemorrhagic fever with renal syndrome

“…It may influence platelet aggregation and initiates a series of intracellular signaling pathways, resulting in a number of events, including reorganization of the cytoskeleton and clot retraction [45]. Thus, it is possible that HPA-3 may in some way modulate platelet-fibrinogen interactions, regulate the postfibrinogen binding events, and subsequently influence clot resolution [46].…”

Association of Human Platelet Alloantigen 1 through 5 Polymorphisms with Ischemic Stroke

“…The association between HPA polymorphic variants and stroke had previously been reported, but with varied outcomes. HPA-1b was associated with stroke among 153 Israeli patients [24], and HPA-3 a/3b was linked with stroke among Caucasian (UK) cases [25]. A limited association of HPA-2 a/b was also reported in an Australian study [26], and a mild association of HPA-1 a/b with stroke was demonstrated in a study on 218 German patients [27].…”

Genetic Variants of Platelet Glycoprotein Receptors and Risk of Stroke in Young Women

“…Given the possible increased in vitro thrombogenicity of the Ser 843 variant, 23 one may speculate that the less adhesive Ile 843 allele is associated with a increased tendency toward embolization of a preexisting platelet thrombus; this might account for increased mortality following the acute atherothrombotic event. 9 Several limitations of our study should be noted. First, the relatively small number of cases and the performance of multiple subgroup analyses may increase the likelihood of a spurious association (type I statistical error).…”

“…[2][3][4][5][6][7][8] Two other common platelet glycoprotein dimorphisms, glycoprotein IIb Ile/Ser 843 and glycoprotein Ia Glu/Lys 505 , were not associated with ischemic stroke in a single study, 7 but the Ile 843 variant of glycoprotein IIb was recently associated with increased mortality following ischemic stroke in an elderly patient population. 9 A nucleotide 807T variant of glycoprotein Ia that correlates with increased platelet surface levels of glycoprotein Ia/IIa (the platelet collagen receptor) 10 was recently associated with an increased risk of ischemic stroke with onset at a young age. 11 The inconsistent results of studies examining the risk of stroke associated with genetic platelet glycoprotein variants may be partly due to differences in demographic characteristics between study populations.…”

“…9 Since our study analyzed only women who survived their acute event, it is possible that the women who died acutely had an overrepresentation of the Ile 843 variant. Given the possible increased in vitro thrombogenicity of the Ser 843 variant, 23 one may speculate that the less adhesive Ile 843 allele is associated with a increased tendency toward embolization of a preexisting platelet thrombus; this might account for increased mortality following the acute atherothrombotic event.…”