Platelet glycoprotein Ib alpha Kozak polymorphism is associated with an increased risk of ischemic stroke

Platelets are pivotal to the process of arterial thrombosis resulting in is chemic stroke. Occlusive thrombosis is initiated by the interaction of von Willebrand factor (vWf) and platelet glycoprotein (GP) Ib alpha. Three poly morphisms have been de scribed in GP Ib alpha (Kozak TIC polymorphism, vari able number of tandem repeats [VMTR], and the human platelet antigen 2a [HP A-2a] [Thr] or HPA-2b [Met] at position 145), each of which may enhance the vWf and GP Ib alpha Interaction. This study investigated whether these pol ymorphisms are candidate genes for first-ever ischemic stroke. A hospital-b ased case-control study was conducted of 219 cases of first-ever ischemic s troke and 205 community controls randomly selected from the electoral roll and stratified by age, sex, and postal code. The subtypes of stroke were cl assified, the prevalence of conventional risk factors was recorded, and blo od was collected to perform genotyping analysis for Kozak C or T alleles, V NTR, and HPA-2a/b. It was found that the Kozak TIC genotype was over-repres ented in the stroke group (32.2%) compared with controls (22.8%) (odds rati o [OR], 1.6; 95% confidence interval [Cr], 1.03-2.54; P < .03), and the ass ociation was still present even after adjusting for conventional risk facto rs. There was a trend in the increased prevalence of HPA-2a/b in stroke pat ients (15%) compared with controls (9.9%) (adjusted OR, 1.8; 95% Cl, 0.94-3 .4; P = .07). No associations were seen with the VMTR polymorphism or with any of the polymorphisms with stroke subtype, It was concluded that the Koz ak T/C polymorphism; which is associated with an increase in platelet GP Ib alpha surface expression, is an independent riskfactorfor first-ever ische mic stroke. (C) 2001 by The American Society of Hematology.