Warfarin is the mainstay of anticoagulation therapy worldwide. Its clinical use, 
however, is complicated by the fact that it has a narrow therapeutic index with 
potential bleeding complications. The dosage requirement of warfarin to produce 
therapeutic anticoagulation varies widely among patients. Recently genetic 
factors such as the CYP2C9 and VKORC1 genes have been demonstrated to be 
determinants of warfarin response. CYP2C9 is the enzyme primarily responsible 
for the metabolic clearance of the S-enantiomer of warfarin. VKORC1 is the 
target protein of warfarin which recycles the reduced form of vitamin K, an 
essential cofactor in the formation of the vitamin K-dependent clotting factors. 
There is strong evidence to support an association between these genetic 
variants and a therapeutic dose of warfarin. On the basis of these observations, 
the Food and Drug Administration (FDA) approved a labeling change for warfarin 
that includes the genetic information of VKORC1 and CYP2C9 as factors 
influencing interindividual variability in warfarin dosing. The package insert 
as of August 2007 states that "lower initiation doses should be considered for 
patients with certain genetic variations in CYP2C9 and VKORC1 enzymes." The FDA 
has also approved clinical tests for these genetic variants. However, at this 
time, validated dosing algorithm and evidence to support the clinical utility of 
genotyping and reliable economic analysis are lacking to recommend for routine 
CYP2C9 and VKORC1 testing in every patiens before the initiation of warfarin 
therapy. In this review, we present the results of several prospective 
randomised controlled trials conducted to test the impact of genotype-guided 
warfarin dosing in Caucasian and Asian patients initiating warfarin.