Pharmacogenetics Newsletter

Volume 1, Issue 8, 08/19/2009

Question

How do known genetic polymorphisms to VKORC1 influence the safety and efficacy of warfarin (Coumadin®, Jantoven®)?

Answer

Ever since its introduction into the market over 50 years ago, warfarin (Coumadin®, Jantoven®) is the most prescribed oral anticoagulant in the prevention and treatment of thromboembolic events in both North America and Europe.(1)  However, it can be one of the more difficult and time consuming medications for clinicians to manage.  In most situations, the desired International Normalized Ratio (INR) goal ranges from 2 to 3 where benefits outweigh the risks for bleeding in most situations.  Factors such as changes in diet, compliance, other medications and comorbidities provide only some of the explanations for the variation in INR that sometimes results in complicated, patient specific dosing regimens.(1)  Two non-changing factors that primarily impact the initial titration phase of warfarin, are genetic polymorphisms of vitamin K 2,3-epoxide reductase complex 1 (VKORC1) gene expression (involved in the "functional activation" of vitamin K dependent clotting factors) and cytochrome P450 (CYP) 2C9.(1,2)

The complete answer to this issue comes with a figure that shows the mechanisms of VKORC1's interaction on warfarin.

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