CE MarkEER056050

50 Tests - 1075 A>C

Available for QiaSymphony SP/AS - Ref: EER056032QS


Warfarin, a derivative of coumarin, is the most widely prescribed anticoagulant for the prevention and treatment of arterial and venous thromboembolic disease, including deep vein thrombosis (DVT), pulmonary embolism (PE), ischemic stroke, myocardial infarction (MI), and atrial fibrillation. However, optimizing the warfarin dose in individual patients is complicated by two factors.

The first factor is the drug’s narrow therapeutic range, which leads to an increased risk of thromboembolism at lower doses and an increased risk of bleeding at higher doses. The second factor is the wide interindividual variability in warfarin response, influenced by multiple factors.

Genetic variants are recognized to explain a large proportion of these factors. In particular, pharmacogenomic studies have identified two SNPs found in the cytochrome P450 enzyme gene CYP2C9 known as CYP2C9*2 (C430T) and CYP2C9*3 (A1075C), along with a third SNP found in the Vitamin K Epoxide Reductase Complex Subunit 1 (VKORC1 1639G>A). The cytochrome P450 (CYP) isozyme 2C9 is the primary enzyme responsible for the metabolism of warfarin, as well as many other drugs.

Variants of CYP2C9 such as CYP2C9*2 and CYP2C9*3 are associated with reduced enzyme activity to metabolize warfarin (and other drugs). Patients carrying at least one copy of such a variant allele (CYP2C9*2 slow metabolizers; CYP2C9*3 poor metabolizers) will need a lower daily warfarin dose than those having normal CYP2C9 activity. The CYP2C9*2 test should be performed in combination with the CYP2C9*3 and VKORC1 (1639G>A) SNPs tests for application to warfarin dose estimates, such as through