OBJECTIVE: To investigate potential contributions of genetic variants of 
cytochrome P-450 2C9 (CYP2C9) and vitamin K expoxide reductase (VKORC1) to the 
anticoagulation response during the initiation of warfarin therapy in the Han 
Chinese population.
METHODS: A total of 798 Han Chinese patients received long-term warfarin 
anticoagulant therapy orally after valve replacement in our hospital between 
2000 and 2008 were included in this study. Nine single nucleotide polymorphism 
(SNP) loci [rs12572351 G > A, rs9332146 G > A, rs4917639 G > T, rs1057910 A > C 
(CYP2C9(*)3), rs1934967 G > T, rs1934968 G > A, rs9923231 C > T (VKORC1-1639 G > 
A), rs2359612 G > A and rs10871454 C > T] in 2 genes including CYP2C9 and 
VKORC1, which were possibly correlated with warfarin pharmacokinetics and 
pharmacodynamics through literature retrieval, were selected and analyzed. 
Warfarin steady-state dose requirement, time to the INR (the international 
normalized ratio) within the therapeutic range and percent of the INR of more 
than 3.5 were compared among genotype subgroups. SNaPshot technique was used to 
detect gene SNPs; Hardy-Weinberg genetic equilibrium test was used to test 
population representativeness.
RESULTS: CYP2C9(*)3 genotype did not affect the required warfarin dose while it 
was associated with increased risk of bleeding when treated with routine dosage 
regimen during the initiation of treatment. The allelic mutation frequency at 
VKORC1 gene rs10871454G > A and VKORC1-1639G > A SNP loci was 92.04% and 88.03%, 
respectively and rs10871454 was in perfect linkage disequilibrium with-1639. 
Patients with VKORC1 rs10871454 genetic mutation required lower warfarin dose in 
the first 28 days of therapy. VKORC1-1639 genetic polymorphism was also 
associated with shorter time to the INR within the therapeutic range and 
increased risk of over-anticoagulation.
CONCLUSION: Detecting genetic polymorphism of CYP2C9 and VKORC1 could guide 
clinical use of warfarin to reduce the risk of adverse reactions including 
bleeding in patients receiving chronic anticoagulation therapy.