[Association between CYP2C9 and VKORC1 genetic polymorphism and warfarin dose requirements].

OBJECTIVE

To assess the contribution of vitamin K epoxide reductase complex 1 (VKORC1) and cytochrome P450 2C9 (CYP2C9) genotype, age, body size, height, and weight to warfarin dose requirement.

METHODS

Blood samples were collected from 191 patients receiving warfarin therapy. Patients's age, gender, height, and weight were registered. PCR-RFLP method was used for the detection of VKORC1-1639G > A and CYP2C9 genotype.

RESULTS

VKORC1-1639G > A genotyping showed that 159 patients were homozygous AA, 31 were heterozygous GA, and 1 was homozygous GG genotype. CYP2C9 genotyping showed that 176 patients were *1/*1, 15 patients were heterozygous *1/3. Patients with VKORC1-1639 (G > A) GG + GA genotype required a significantly higher warfarin dose than those with AA genotype [(3.36 +/- 0.97) mg/d vs. (1.75 +/- 0.56) mg/d, P < 0.01], and patients with CYP2C91/1 genotype also required a higher warfarin dose than those with CYP2C91/*3 genotype [(2.06 +/- 0.83) mg/d vs. (1.55 +/- 1.32) mg/d, P < 0.05]. The multiple linear regression model for warfarin dose indicated age, weight and VKORC1 genotype could explain the inter-individual variation in dose requirement of 9.3%, 7.4%, 51.9% patients, respectively; age, weight, CYP2C9 and VKORC1 genotype together could explain the inter-individual variation in dose requirement of 64.1% patients.

CONCLUSION

This study showed that age, weight and VKORC1 and CYP2C9 polymorphism had significant influences on warfarin dose requirements and should be considered on dosing regimens modification to improve the safety of warfarin therapy.