Association between platelet glycoprotein Ibα genotype and ischemic cerebrovascular disease

Background and Purpose - Platelets play pivotal roles in the development of ischemic cerebrovascular disease (CVD). The platelet glycoprotein (GP) Ib/IX/V complex is a receptor for von Willebrand factor, which plays a major role in the initial phase of platelet activation under high shear stress conditions. This study was designed to investigate the association between a genetic variation of this receptor and the prevalence of CVD. Methods - Two hundred patients with ischemic CVD, as confirmed by brain CT and/or MRI, and 317 age- and sex-matched control subjects without clinical evidence of CVD or cardiovascular disease were analyzed for their genotype frequencies of the ¹⁴⁵Thr/Met dimorphism of the α-chain of GPIb (GPIbα). Results - Genotypes with ¹⁴⁵Met (T/M and M/M) were more frequently found in the CVD patients (26.5%) than in control subjects (14.2%, P=0.0005). The genotype effect was more obvious in those <60 years of age or without acquired cardiovascular risk factors. The odds ratio for nonsmoking women <60 years of age was 10.6 (95% confidence intervals, 2.2 to 51.7). Although the number of patients studied was small (n=24), transient ischemic attack showed the highest odds ratio (4.3, P=0.0004), followed by lacunar infarction (OR=2.2, P=0.0024) and atherothrombotic infarction (OR=1.5, P=0.3143). Logistic regression analysis revealed that the presence of Met-allele was independently associated with CVD. Conclusions - Our study suggests that the platelet GPIbα genotype is a genetic risk factor for ischemic CVD.