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.