Establishment And Clinical Application Of Detection For The Warfarin-related Genes

Warfarin is the most commonly prescribed anticoagulant drug for the prophylaxis and treatment of venous and arterial thromboembolic disorders. The effectiveness and safety of warfarin is critically dependent on maintaining the prothrombin time, expressed as the international normalized ratio (INR), within the therapeutic range. However the proper dose of the drug is very hard to determine and varies widely among individuals.It requires careful clinical management to balance the risks of over-anticoagulation and bleeding with those of under-anticoagulation and clotting. A patient’s race, age, sex, weight, and genetic variants may all contribute to warfarin-dose requirements. Many current studies have found that genetic factors as vitamin K epoxide reductase complex subunit 1 gene (VKORC1)and cytochrome P2C9 (CYP2C9) play at least partial roles in loading and maintenance warfarin dose. They have also developed some individualized dosing algorithms. However, most of these studies focused on the non-Han-population, while racial differences also seem to be important, and few studies valuate their algorithm prospectively. The aim of our study is to examine the distribution of warfarin-dosing-related single nucleotide polymorphisms (SNPs) in Han-population, establish a multivariate regression model for estimating warfarin dose incorporating genetic and demographic factors that could affect warfarin-dose requirements, with the view to developing a novel individualized dosing algorithm and valuate the practicability of our rgimen in clinical application prospectively.