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Blood, 15 February 2001, Vol. 97, No. 4, pp. 875-879
CLINICAL OBSERVATIONS, INTERVENTIONS, AND THERAPEUTIC TRIALS
The Kozak sequence polymorphism of platelet glycoprotein Ib
and risk of nonfatal myocardial infarction and nonfatal stroke in
young women
Michele B. Frank,
Alexander
P. Reiner,
Stephen M. Schwartz,
Prasanna N. Kumar,
Rachel M. Pearce,
Patrick G. Arbogast,
W. T. Longstreth Jr,
Frits R. Rosendaal,
Bruce M. Psaty, and
David S. Siscovick
From the Division of Hematology, Department of
Medicine, University of Washington, Seattle, WA; Cardiovascular Health
Research Unit, Department of Medicine and Department of Epidemiology,
University of Washington, Seattle, WA; Department of Pathology, PSG
Institute of Medical Sciences and Research, Coimbatore, Tamil Nadu,
India; Department of Biostatistics and Department of Neurology,
University of Washington, Seattle, WA; the Hemostasis and Thrombosis
Research Center and Department of Clinical Epidemiology, University
Hospital Leiden, The Netherlands.
Several platelet membrane glycoprotein polymorphisms have been
identified as potential risk factors for cardiovascular disease. Recently a nucleotide 5T/C dimorphism in the translation initiation site (Kozak sequence) of the platelet glycoprotein Ib
(GPIb ) gene was associated with increased platelet
surface levels of the GPIb-IX-V receptor complex. The role of this
GPIb Kozak sequence polymorphism in the occurrence of arterial
thrombotic disease is unknown. We performed genotype analysis of the
Kozak sequence polymorphism of GPIb in a population-based study of
18- to 44-year-old women with nonfatal myocardial infarction (MI)
(n = 78), nonfatal stroke (n = 106), and 384 demographically
similar female control subjects. Analysis of 5T/C genotypes revealed
that at least one copy of the C allele was present in 14.1% of MI
cases, 23.6% of stroke cases, and 23.7% of controls. The age-adjusted
odds ratio for MI in women carrying at least one copy of the C allele
was 0.53 (95% confidence interval [CI] 0.27-1.05). The age-adjusted odds ratio for stroke in women carrying at least one copy of the C
allele was 0.99 (95% CI 0.59-1.65). Analyses stratified by stroke type
(ischemic, hemorrhagic) yielded similar results. In conclusion, young
women carrying the C allele of the Kozak sequence polymorphism of
GPIb are not at increased risk of MI or stroke. Paradoxically, the C
allele may even be associated with a reduced risk of MI in this
population. This finding requires further study.

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