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  • Title: Platelet GPIbalpha, GPIV and vWF polymorphisms and fatal pre-hospital MI among middle-aged men.
    Author: Pellikka M, Narhi L, Perola M, Penttila A, Karhunen PJ, Mikkelsson J.
    Journal: J Thromb Thrombolysis; 2008 Oct; 26(2):91-6. PubMed ID: 17619827.
    Abstract:
    BACKGROUND: The binding of platelet glycoprotein (GP) Ib-IX-V receptor complex to subendothelial collagen via von Willebrand factor is the initial step of the formation of platelet thrombi following atherosclerotic plaque rupture. Platelet GPIV binds to collagen and/or thrombospondin and further activates platelets. Genetic variation in these proteins could associate with platelet aggregability and the risk of myocardial infarction (MI). METHODS AND RESULTS: We studied the associations of polymorphisms of GPIbalpha, GPIV and von Willebrand factor with the extent of coronary atherosclerosis, coronary narrowing, and fatal MI in an autopsy series of 300 middle-aged, Caucasian Finnish men who had suffered sudden out-of-hospital death. 31% of men with MI under the age of 50 carried the GPIbalpha HPA-2 ThrThr/Kozak TT haplotype as opposed to 62% of control men (OR 0.27, 95% CI 0.08-0.93, P = 0.03). In addition, 7% of men with MI under the age of 50 carried the GPIV AA genotype versus 29% of control men (OR 0.16, 95% CI 0.03-0.98, P < 0.05). These associations were not due to any effects of these gene variants on the coronary atherosclerotic changes. The G/A polymorphism of the von Willebrand factor gene failed to show any association with MI or coronary atherosclerosis in this series of men. CONCLUSIONS: The combined ThrThr/TT haplotype of GPIbalpha as well as the AA genotype of GPIV seem to decrease the risk of fatal MI among men during early middle-age.
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