Detection of functional differences between different platelet membrane qlycoprotein Ibα variable number tandem repeat and Kozak genotypes as shown by the PFA-100 system

摘要

The interaction between the platelet membrane glycopro-tein Ib/IX/V and von Willebrand factor (VWF) is the primary event in the formation of an occlusive thrombus under conditions of high shear stress. Several polymorphisms of glycoprotein Ibα (the functional binding site for surface bound VWF) have been reported. The relation of variable number tandem repeat (VNTR) and Kozak sequence polymorphisms with arterial thrombosis and coronary artery disease remains controversial. In our recent study we proposed that the glycoprotein Ibα genotypes CC of the VNTR and Kozak — 5TT increased the risk of platelet plug formation under the condition of high shear stress generated by stenosed vessels and thus caused the increased risk of myocardial infarction (MI), which we observed in a group of patients with known coronary artery disease status who had those genotypes. We also observed the potential protective effect of the glycoprotein Ibα Kozak -5TC genotype. The objective of this study was to evaluate the effect of these polymorphisms on platelet function of the same group of patients by using the platelet function analyser system PFA-100 (Dade Behring), which mimics physiological conditions in vivo involving platelet binding to VWF and platelet adhesion/aggregation in response to collagen under conditions of high shear after activation by adrenaline (epinephr-ine) or ADP.