Platelet glycoprotein Ibalpha Kozak polymorphism is associated with an increased risk of ischemic stroke.
Platelets are pivotal to the process of arterial thrombosis resulting in ischemic stroke. Occlusive thrombosis is initiated by the interaction of von Willebrand factor (vWf) and platelet glycoprotein (GP) Ibalpha. Three polymorphisms have been described in GP Ibalpha (Kozak T/C polymorphism, variable number of tandem repeats [VNTR], and the human platelet antigen 2a [HPA-2a] [Thr] or HPA-2b [Met] at position 145), each of which may enhance the vWf and GP Ibalpha interaction. This study investigated whether these polymorphisms are candidate genes for first-ever ischemic stroke. A hospital-based case-control study was conducted of 219 cases of first-ever ischemic stroke and 205 community controls randomly selected from the electoral roll and stratified by age, sex, and postal code. The subtypes of stroke were classified, the prevalence of conventional risk factors was recorded, and blood was collected to perform genotyping analysis for Kozak C or T alleles, VNTR, and HPA-2a/b. It was found that the Kozak T/C genotype was over-represented in the stroke group (32.2%) compared with controls (22.8%) (odds ratio [OR], 1.6; 95% confidence interval [CI], 1.03-2.54; P <.03), and the association was still present even after adjusting for conventional risk factors. There was a trend in the increased prevalence of HPA-2a/b in stroke patients (15%) compared with controls (9.9%) (adjusted OR, 1.8; 95% CI, 0.94-3.4; P =.07). No associations were seen with the VNTR polymorphism or with any of the polymorphisms with stroke subtype. It was concluded that the Kozak T/C polymorphism, which is associated with an increase in platelet GP Ibalpha surface expression, is an independent risk factor for first-ever ischemic stroke.
Baker
R I
RI
Thrombosis and Haemophilia Service and Stroke Unit, Royal Perth Hospital, Department of Medicine, University of Western Australia, Perth, Australia. rossco@cyllene.uwa.edu.au
Eikelboom
J
J
Lofthouse
E
E
Staples
N
N
Afshar-Kharghan
V
V
López
J A
JA
Shen
Y
Y
Berndt
M C
MC
Hankey
G
G
D000368:Aged; D002545:Brain Ischemia / Q000453:epidemiology / Q000209:etiology / Q000235:genetics; D016022:Case-Control Studies; D005260:Female; D005787:Gene Frequency; D005820:Genetic Testing; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D019038:Platelet Glycoprotein GPIb-IX Complex / Q000235:genetics*; D011110:Polymorphism, Genetic; D021122:Protein Subunits; D012307:Risk Factors; D020521:Stroke / Q000453:epidemiology / Q000209:etiology / Q000235:genetics*; D020080:Tandem Repeat Sequences
D019038:Platelet Glycoprotein GPIb-IX Complex; D021122:Protein Subunits