Volume 28, Issue 9 p. 1084-1097

Warfarin Pharmacogenetics

Dr. Nita A. Limdi Pharm.D., Ph.D., M.S.P.H.

Corresponding Author

Dr. Nita A. Limdi Pharm.D., Ph.D., M.S.P.H.

Department of Neurology, University of Alabama, Birmingham, Alabama.

Department of Neurology, University of Alabama at Birmingham, 1719 6th Avenue South, CIRC-312, Birmingham, AL 35294-0021; e-mail: [email protected].Search for more papers by this author
Dr. David L. Veenstra Pharm.D., Ph.D.

Dr. David L. Veenstra Pharm.D., Ph.D.

Pharmaceutical Outcomes Research and Policy Program and Institute for Public Health Genetics, University of Washington, Seattle, Washington.

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First published: 06 January 2012
Citations: 104


Significant interest in the pharmacogenetics of warfarin therapy has been triggered with the recent package insert update that highlights the potential role of pharmacogenetics in improving the safety and effectiveness of warfarin. We review the evidence of the influence of the two key genes of interest, the cytochrome P450 2C9 gene, CYP2C9, and the vitamin K epoxide reductase complex 1 gene, VKORC1, on warfarin response and discuss the implications of current knowledge for clinical practice. The influence of CYP2C9 and VKORC1 genotypes on warfarin dose requirements has been consistently demonstrated in diverse racial and ethnic patient groups in observational studies and randomized clinical trials. Dosing algorithms have been developed that incorporate clinical, demographic, and genetic information to help select a warfarin starting dose. Furthermore, CYP2C9 variant genotypes have been associated with a significantly increased risk of serious bleeding events. However, evidence to date from prospective, controlled studies has not demonstrated an added benefit of incorporating genotype-guided therapy in improving anticoagulation control or in preventing or reducing the risk of hemorrhagic or thromboembolic complications. Research efforts designed to evaluate the effectiveness of genotype-guided therapy in improving outcomes are under way. However, the routine use of CYP2C9 and VKORC1 genotyping in the general patient population who begin warfarin therapy is not supported by evidence currently available.