| Platelet aggregation plays a pivotal role in the pathogenesis of arterial thrombosis, such as ischemic stroke (IS) and acute myocardial infarction (AMI). Platelet aggregation is initiated by several agonists that act via different platelet receptors. Polymorphisms in these platelet receptor genes may influence the extent of platelet aggregation and therefore these polymorphisms may be associated with the risk of arterial thrombosis. Drugs inhibiting platelet aggregation are widely used as secondary prophylaxis in patients with AMI and IS. A new class of anti-platelet drugs are the ADP receptor blockers, the thienopyridines, including clopidogrel and ticlopidin. Normally the activation of platelets by ADP results in platelet aggregation and stabilization of existing aggregates. ADP-dependent platelet aggregation requires activation of two G-protein coupled receptors. One of these, the P2Y12 receptor, is the target of thienopyridines. Recently the P2Y12 gene has been cloned. Because polymorphisms in the gene encoding the ADP receptor may influence the function of the receptor, it is of extreme interest to identify polymorphisms in the P2Y12 gene. It is likely that genetic mutations or polymorphisms in the ADP receptor gene affect the function of this receptor and possibly also the efficacy of the thienopyridines. The aim of this research project is to identify polymorphisms in the recently cloned gene of the P2Y12 ADP receptor, to investigate whether these result in enhanced platelet aggregability and to study the association of the polymorphisms with arterial thrombosis. This may lead to new insights on treatment of patients suffering from arterial thrombosis with thienopyridines. This study is supported by the Netherlands Organisation for Scientific Research (NWO). |
