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Decisions about initial dosing of warfarin are influenced by patient age, concurrent medications, diet, and comorbid diseases. Despite dose modifications based on these considerations, many patients receive initial dosing that is too high or too low and can experience serious consequences, such as bleeding or new thrombi. During the past few years, researchers have reported that polymorphisms in the genes whose products interact with warfarin can have marked clinical effects. For example, vitamin K epoxide reductase C1 (VKORC1) is critical for the formation of functional clotting factors and is inhibited by warfarin, and cytochrome P-2C9 (CYP2C9) degrades warfarin.
To assess the effects of these genetic variations on warfarin management, inv…