Warfarin response

Warfarin is an oral anti-coagulant used world-wide to treat and prevent thrombotic disorders. While it is highly effective, it has a very narrow therapeutic index making it difficult to dose correctly. Genetic variants in both cytochrome P450-2C9 (CYP2C9) and vitamin K-epoxide reductase complex (VKORC1) enzymes, along with non-genetic factors, are known to affect warfarin dose variability. Patients with specific variants in the gene CYP2C9 (the primary warfarin-metabolizing enzyme), such as CYP2C9*2 and CYP2C9*3, may require a lower dose of warfarin as compared to patients without these variants. Patients with a specific variant in VKORC1 (the target enzyme of warfarin), known as -1639G>A or rs9923231, may require a lower warfarin dose as compared to patients who do not have this variant. The combination of CYP2C9 and VKORC1 genetic variants, along with clinical factors, can put some patients at risk for adverse events such as bleeding. Guidelines regarding the use of pharmacogenomic tests in dosing for warfarin have been published in Clinical Pharmacology and Therapeutics by the Clinical Pharmacogenetics Implementation Consortium (CPIC) and are available on the PharmGKB website.

PharmGKB