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(Stroke. 1999;30:2606.)
© 1999 American Heart Association, Inc.

Original Contributions

Association of the Platelet Glycoprotein IIb HPA-3 Polymorphism With Survival After Acute Ischemic Stroke

Angela M. Carter, PhD; Andrew J. Catto, MRCP; John M. Bamford, MD Peter J. Grant, MD

From the Unit of Molecular Vascular Medicine, Research School of Medicine, University of Leeds, Leeds General Infirmary, and Department of Neurology, St. James’ University Hospital (J.M.B.), Leeds, UK.

Correspondence to Peter J. Grant, Unit of Molecular Vascular Medicine, Research School of Medicine, G Floor, Martin Wing, Leeds General Infirmary, Leeds, LS1 3EX, UK.

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 Pl^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.

Key Words: mortality • platelet glycoprotein GPIIb/IIIa complex • polymorphism (genetics) • stroke, ischemic

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