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Blood, 1 July 2001, Vol. 98, No. 1, pp. 36-40
CLINICAL OBSERVATIONS, INTERVENTIONS, AND THERAPEUTIC TRIALS
Platelet glycoprotein Ib Kozak polymorphism is
associated with an increased risk of ischemic
stroke
Ross I. Baker,
John Eikelboom,
Elizabeth Lofthouse,
Nicole Staples,
Vahid Afshar-Kharghan,
José A. López,
Yang Shen,
Michael C. Berndt, and
Graeme Hankey
From the Thrombosis and Haemophilia Service and Stroke
Unit, Royal Perth Hospital, Department of Medicine, University of
Western Australia, Perth, Australia; the Preventative Cardiology and
Therapeutics Program, McMaster University, Hamilton, Canada; the Baker
Medical Research Institute, Melbourne, Australia; and the Thrombosis
Research Section, Department of Medicine, Baylor College of Medicine,
Houston, TX.
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) Ib . Three polymorphisms have been described in GP Ib (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 Ib
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 Ib surface expression,
is an independent risk factor for first-ever ischemic stroke.
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