Association of the platelet glycoprotein IIb HPA-3 polymorphism with survival after acute ischemic stroke.
OBJECTIVE
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.
Carter
A M
AM
Unit of Molecular Vascular Medicine, Research School of Medicine, University of Leeds, Leeds General Infirmary, and Department of Neurology, St. James' University Hospital, Leeds, UK.
Catto
A J
AJ
Bamford
J M
JM
Grant
P J
PJ
D000368:Aged; D016824:Antigens, Human Platelet / Q000235:genetics*; D016022:Case-Control Studies; D005260:Female; D005340:Fibrinogen / Q000032:analysis; D005838:Genotype; D006801:Humans; D008297:Male; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000235:genetics*; D019038:Platelet Glycoprotein GPIb-IX Complex; D010980:Platelet Membrane Glycoproteins; D011110:Polymorphism, Genetic; D011956:Receptors, Cell Surface / Q000235:genetics*; D020521:Stroke / Q000097:blood / Q000235:genetics* / Q000401:mortality; D001620:beta-Thromboglobulin / Q000032:analysis
C044561:3a alloantigen, human; C083448:3b alloantigen, human; D016824:Antigens, Human Platelet; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D019038:Platelet Glycoprotein GPIb-IX Complex; D010980:Platelet Membrane Glycoproteins; D011956:Receptors, Cell Surface; D001620:beta-Thromboglobulin; C032193:glycoprotein receptor GPIb-IX; D005340:Fibrinogen