Platelet GP IIIa Pl ^A and GP Ib Variable Number Tandem Repeat Polymorphisms and Markers of Platelet Activation in Acute Stroke

Abstract

Abstract-A number of polymorphisms of the platelet glycoprotein (GP) Ib-V-IX and IIb/IIIa complexes have been described, and the Pl A polymorphism of GP IIIa has been associated with coronary thrombosis. We determined the levels of ␤-thromboglobulin (␤-TG) and platelet factor 4 (PF4) and the genotype distributions of Pl A and a variable number tandem repeat (VNTR) polymorphism of GP 1b in subjects with acute stroke (nϭ609) and healthy control subjects (nϭ435). Levels of ␤-TG were higher in patients both initially (47.4 [44.7 In a logistic regression model, ␤-TG remained an independent predictor of poststroke mortality, with an odds ratio for an increase in 10 ng/mL of 1.12 (1.03 to 1.21, Pϭ0.006). In subjects who had never smoked, there was a significant difference in the genotype distributions of patients with atherothrombotic stroke (A1/A1ϭ147, A1/A2ϭ70, and A2/A2ϭ2) compared with controls (A1/A1ϭ165, A1/A2ϭ47, and A2/A2ϭ5, Pϭ0.03). The Pl A distribution of subjects with atherothrombotic stroke before the age of 50 years (A1/A1ϭ19 and A1/A2ϩA2/A2ϭ18) was also significantly different from age-and sex-matched controls (A1/A1ϭ54 and A1/A2ϩA2/ A2ϭ20, Pϭ0.02). We found no association of VNTR with stroke or poststroke mortality. These data indicate that there is a persistent state of enhanced platelet activation in subjects with acute stroke, which is associated with poststroke mortality. The increased frequency of the Pl A2 allele in young subjects with atherothrombotic stroke lends further support for a role of the Pl A polymorphism in acute thrombosis. 1,2 Under conditions of high shear stress associated with atherosclerotic narrowing of vessels, GP Ib-V-IX (GP 1b) complex binds vWF exposed at sites of endothelial cell disruption.3 This interaction results in platelet adhesion and activation and the expression of functional GP IIb/IIIa complexes (␣ IIb ␤ 3 integrin) on the platelet surface.2 GP IIb/IIIa exists in an inactive state on resting platelets, but GP Ib/vWF interaction results in a conformational change within GP IIb/IIIa, which then binds fibrinogen and vWF, resulting in platelet aggregation.

Prevalence Of Thrombophilic Mutations In Ischemic Stroke Patients In Isparta, Turkey

“…HPA polymorphisms are associated with stroke; heterozygosity for the GP 3a A2 allele is a risk factor for atherosclerotic stroke in young individuals, and the HPA3 b/b polymorphism and homozygosity for the HPA1b polymorphism are associated with ischemic stroke (65)(66)(67). However, HPA polymorphisms are not associated with hemorrhagic stroke, and the GP 3a A2 allele is not a risk for myocardial infarction, stroke, or venous thrombosis (67,68).…”

Association Between Platelet Glycoprotein Ibα Genotype and Ischemic Cerebrovascular Disease

“…27 In one of these studies, the genotype effect of the PlA1/A2 polymorphism was more obvious among women, 28 and in the other study, the genotype effect was stronger in nonsmokers. 23 Thus the relative contribution of genetic factors might differ significantly, depending on the populations analyzed. This might in part explain the conflicting results of the published studies.…”

“…20 Subsequently, several studies were reported, but only a few studies focused on the association of this genotype with stroke, and the results were not consistent. [21][22][23] Therefore we performed an allelic association study to compare genotype frequencies between CVD patients and age-and sex-matched control subjects.…”

Hypothermia‐induced platelet aggregation in heparinized flowing human blood: Identification of a high responder subpopulation

“…The PL A2 polymorphism has been identi®ed in 10À21% of the Caucasian population [38À41]. The presence of the PL A2 allele has been associated with increasing platelet sensitivity to platelet agonists [42] and has been proposed as a hemostatic risk factor associated with arterial thrombotic disease [38,43] and neurological damage [39,44,45]. The reported allele frequency is similar to the frequency of donors exhibiting HIPA, and a DNA analysis was performed using a previously published protocol [41] to determine if a correlation between the PL A2 allele and HIPA exists.…”