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).

We studied the associations of polymorphisms of GPIbα, 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 GPIbα 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.

The combined ThrThr/TT haplotype of GPIbα as well as the AA genotype of GPIV seem to decrease the risk of fatal MI among men during early middle-age.