The Kozak sequence polymorphism of platelet glycoprotein Ib alpha and riskof nonfatal myocardial infarction and nonfatal stroke in young women

Several platelet membrane glycoprotein polymorphisms have been identified a s potential risk factors for cardiovascular disease. Recently a nucleotide -5T/C dimorphism in the translation initiation site (Kozak sequence) of the platelet glycoprotein Ib alpha (GPIb alpha) gene was associated with incre ased platelet surface levels of the GPIb-IX-V receptor complex. The role of this GPIb alpha Kozak sequence polymorphism in the occurrence of arterial thrombotic disease is unknown. We performed genotype analysis of the Kozak sequence polymorphism of GPIb alpha in a population-based study of 18- to 4 4-year-old women with nonfatal myocardial infarction (MI) (n = 78), nonfata l stroke (n = 106), and 384 demographically similar female control subjects . Analysis of -5T/C genotypes revealed that at least one copy of the C alle le was present in 14.1% of MI cases, 23.6% of stroke cases, and 23.7% of co ntrols. The age-adjusted odds ratio for MI in women carrying at least one c opy 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 t he C allele was 0.99 (95% CI 0.59-1.65). Analyses stratified by stroke type (ischemic, hemorrhagic) yielded similar results. In conclusion, young wome n carrying the C allele of the Kozak sequence polymorphism of GPIb alpha ar e not at increased risk of MI or stroke. Paradoxically, the C allele may ev en be associated with a reduced risk of MI in this population. This finding requires further study. (C) 2001 by The American Society of Hematology.