Impact of platelet glycoprotein Ibalpha Kozak polymorphism on risk of ischemic cerebrovascular events

Abstract number: P0387

Hsieh K., Unger P., Endler G., Reisinger M., Janisiw M., Lalouschek W., Lang W., Mannhalter C.

University of Vienna, Austria

Background  

Primary hemostasis and platelet activity have been shown to play a central role in arterial thrombosis resulting in myocardial infarction or ischemic stroke. Platelet adhesion to the vascular wall and platelet aggregation are initiated by the interaction of platelet glycoproteins (GPIa, GPIbalpha, GPIIb/IIIa), collagen and von Willebrand factor (vWF). Recently, a T/C polymorphism in the Kozak sequence of the GPIb gene has been identified. In individuals carrying the CC genotype an increased number of GPIb molecules on the platelet surface has been reported. In contrast, an increased platelet agreeability under high shear stress has been observed in TT carriers. To assess the importance of this genotype for the development of stroke, we performed a case-control study on 1364 Austrian individuals.

Patients and methods  

A total of 430 patients with ischemic stroke or transient ischemic attack (TIA) from the Vienna stroke registry (age: median 53, interquartile range: 45–57 years; 278 men, 152 women) and 924 healthy controls (45, 37–54 years; 478 men, 446 women) were analyzed for the prevalence of the Kozak T/C polymorphism using a mutagenically separated PCR.

Results  

The genotype distribution in the control population was 71.2% for T/T, 27.3% for T/C, and 1.5% for C/C, whereas in patients it was 76.0% T/T, 20.8% T/C, and 3.2% C/C. C/C allele carriers were rare and were therefore not considered as separate group in the analyses. We observed a significant difference in the prevalence of T/T between patients and controls in a univariate recessive model (OR 1.4, 95% CI: 1.1–1.9, P = 0.016). The association of the T/T genotype with stroke remained significant also after adjustment for conventional risk factors (hypertension, diabetes mellitus, body mass index, age (in quintiles), hyperlipidemia, sex, and smoking) (adjusted OR: 1.5, 95% CI 1.1–2.1, P = 0.018).

Conclusion  

We conclude from our data that carriers of the TT genotype in the GP Ib gene are at higher risk to develop ischemic events compared to C/T carriers. This is in line with our previous observation that in T/T carriers collagen-epinephrine induced Closure Time is significantly shorter under high shear stress.