Warfarin and other coumarin anticoagulants are widely used clinically, but 
currently dosing is determined individually on the basis of patient response. 
There is increasing evidence that genetic factors, together with several 
non-genetic patient-specific factors, are important determinants of stable dose 
requirement for these compounds. Genotype for CYP2C9, which encodes the main 
cytochrome P450 enzyme that metabolizes warfarin, and VKORC1, the gene encoding 
the warfarin target vitamin K epoxide reductase, together account for 
approximately 30% of the variability in dose requirement. The past two years 
have seen several advances in the area of genetic factors affecting coumarin 
anticoagulant response. In particular, prospective studies have taken place to 
analyze whether earlier small retrospective studies can be confirmed, and the 
question of whether genes other than CYP2C9 and VKORC1 are important in 
determining dose requirement has been examined. So far, no strong evidence that 
other genes contribute to dose requirement has been found, apart from a minor 
but novel role for another cytochrome P450 gene, CYP4F2. A recently published 
whole genome association study confirms that the main genes important in 
warfarin response are CYP2C9 and VKORC1. Clinical trials comparing 
genotype-guided and conventional warfarin initiation have suggested that 
genotyping may be of value, but larger studies are still needed to show clear 
clinical benefit. Current knowledge of genetic factors affecting other coumarin 
anticoagulants is more limited and this area requires further study, as does the 
impact of ethnic variation in genes relevant to coumarin responses. Here we 
review recent advances in the area of coumarin anticoagulant genetics and its 
potential clinical application.