Variability of warfarin dose response associated with CYP2C9 and VKORC1 gene polymorphisms in Chinese patients

Abstract

Objective To investigate the prevalence and implication of cytochrome P450, family 2, subfamily C, polypeptide 9 ( CYP2C9) variants and vitamin K epoxide reductase complex, subunit 1 ( VKORC1)-1639 G > A polymorphisms in Chinese patients receiving warfarin therapy. Methods Chinese Han patients requiring oral warfarin therapy were consecutively enrolled. Correlations between CYP2C9*1, *2, *3, *4, *5 variants and VKORC1-1639 G > A polymorphisms, fourth-day international normalized ratios (INRs) and warfarin maintenance dose were investigated. Results Out of 101 patients, there were no significant differences in fourth-day INR or warfarin daily maintenance doses between patients with CYP2C9*1*1 and CYP2C9*1*3 genotypes. Patients with the VKORC1-1639 AA genotype had a higher fourth-day INR (1.87 ± 0.14) than those with the VKORC1-1639 AG genotype (1.32 ± 0.15). Warfarin maintenance dose for patients with the VKORC1-1639 AA genotype (2.40 ± 0.70 mg/day) was significantly lower than for patients with the VKORC1-1639 AG genotype (4.83 ± 0.70 mg/day). Conclusions Unlike Caucasian populations, VKORC1-1639 G > A polymorphisms in the Chinese population may be the dominant genetic factors associated with warfarin response variability.