Genetic variants in the endothelial protein C receptor gene: reaching significance

Summary

Since the discovery of activated protein C (APC) resistance, mutations and genetic variants in the protein C pathway have been put into the spotlight of research in the pathophysiology of haemostasis. Although none of the more recently discovered mutations in the components of the natural anticoagulant pathways have equalled the clear-cut effect of factor V Leiden in thrombosis and its epidemiological importance, some recent work in several genes of the pathway have shown promising results in linking genotype and phenotype which could explain certain mechanisms in respective thrombosis associated pathologies. The discovery of a specific endothelial protein C receptor (EPCR) and the deciphering of its importance in the biology of protein C, opened up the possibility that genetic variants in the EPCR gene (PROCR) could play a role in the risk for thrombosis (1, 2). The EPCR functions to enhance the activation of anticoagulant protein C by the thrombin-thrombomodulin complex, and it is essential for the interaction of protein C with protease activated receptor 1. In this way, the EPCR acts in the anticoagulant, profibrinolytic and anti-inflammatory response (1, 3, 4). EPCR knock-out mice show early embryonic lethality (5), although a small amount of EPCR is sufficient to maintain the animals alive and fertile (6) …

• References

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