A2 alelle of GpIIIa gene is a risk factor for stroke caused by large-vessel disease in males.

BACKGROUND AND PURPOSE Glycoprotein IIIa (GpIIIa) is a platelet membrane receptor for fibrinogen and von Willebrand factor. It plays a key role in platelet aggregation. Previous studies in stroke patients, without analysis based on specific subtypes of stroke cause, have not shown any link between GpIIIa A1/A2 polymorphism and stroke risk. We studied the significance of the GpIIIa gene A1/A2 polymorphism in stroke patients with different stroke causes. METHODS We genotyped 92 patients with stroke caused by large-vessel disease (LVD stroke) and 184 matched controls; 103 patients with stroke caused by small-vessel disease (SVD stroke) and 206 controls; and 182 patients with cardioembolic stroke (CE stroke) and 182 controls (TOAST criteria). The GpIIIa A1/A2 polymorphism was analyzed by polymerase chain reaction followed by restriction enzyme digestion and electrophoresis. RESULTS The genotype distribution of the GpIIIa gene in patients with LVD stroke (A1/A1, 63%; A1/A2, 34.8%; A2/A2, 2.2%) differed significantly from their controls (A1A1, 79.3%; A1/A2, 20.1%; A2/A2, 0.6%). The distribution of the GpIIIa A1/A2 polymorphism in patients with SVD stroke and CE stroke was similar to that of their controls. In contrast to females with LVD stroke, we found that males with LVD stroke presented with an overrepresentation of at least 1 A2 allele of the GpIIIa gene when compared with their controls (39.7% versus 23.0%; P=0.003). Conditional logistic regression analysis showed that possession of at least 1 A2 allele of the GpIIIa gene was an independent risk factor for LVD stroke in males (OR, 2.51; 95% CI, 1.21 to 5.20). CONCLUSIONS A2 allele of the GpIIIa gene is an independent risk factor for LVD stroke in males.