Platelet glycoprotein IIb/IIIa polymorphism HPA-3 b/b is associated with increased risk of ischemic stroke in patients under 60 years of age

BACKGROUND: The role of genetic risk factors in ischemic stroke is unclear. Platelet glycoprotein IIb/IIIa (GpIIb-IIIa) has been implicated in the pathogenesis of ischemic stroke. We sought to evaluate the relationship between the GpIIb/IIIa complex gene polymorphism and ischemic stroke. MATERIAL/METHODS: We investigated the association of the GpIIb/IIIa complex gene polymorphism with stroke risk in 306 patients with acute ischemic stroke and 266 control subjects by determining the GpIIb and GpIIIa genotype from leukocyte DNA by polymerase chain reaction (PCR) followed by FokI and ScrFI digestion, respectively. RESULTS: Compared with controls, more patients presented with coronary heart disease, hypertension, smoking history, and diabetes. In addition, the patients had higher levels of cholesterol and glucose compared with the control subjects. All donors in the GpIIIa (n=572) group expressed the GpIIIa Pl(A1) (HPA-1 aa) phenotype. There were no significant differences between the HPA-3 genotype (GpIIb) patient distribution (aa=39.9%, ab=41.4%, bb=28.7%) and healthy control subjects (aa=36.1%, ab=35.0%, bb=28.9%) (P=0.580). Among study participants <60 years, there was a significant difference in the HPA-3 genotype distributions of patients (aa=42.9%, ab=19.8%, bb=37.4%) and healthy control subjects (aa=43.3%, ab=38.8%, bb=17.9%) (P=0.007). Furthermore, HPA-3 b/b increased the risk of ischemic stroke >2-fold (P=0.008). CONCLUSIONS: The GpIIb Ile/Ser(843) gene polymorphism is associated with ischemic stroke among young and middle-aged adults (<60 years), especially males. The GpIIIa Pl(A1) phenotype has no relationship to ischemic stroke.