Abstract
We investigated the influence of genetic polymorphisms of CYP2C9 and VKORC1 genotypes on pharmacokinetic and pharmacodynamics of warfarin as well as established the equation for predicting the maintenance dose of warfarin in Thai population using genetic and non-genetic factors. Genotypes of CYP2C9*2, CYP2C9*3, VKORC1 C1173T and VKORC1 G-1639A were detected by realtime PCR using fluorogenic hybridization probes. The associations between genetic and demographic factors to warfarin dosage were analyzed. CYP2C9 polymorphisms affect warfarin metabolism as shown by significant difference in warfarin clearance while VKORC1 genotypes cause significant difference in Warfarin Sensitivity Index (INR:Cp). The mean weekly warfarin dose was statistically significant different among different VKORC1 and CYP2C9 genotypes. Patients with VKORC1 BB haplotype and CYP2C9 *1/*1 required about two times of warfarin dose compared to those with VKORC1 AA haplotype and CYP2C9 *1/*1. Using stepwise multiple linear regression, clinical factors; age and weight, including genetic factors; CYP2C9 and VKORC1, could explain about 53.8% of the variance of warfarin maintenance dose. CYP2C9 and VKORC1 genotypes played important role on the inter-individual variation in warfarin maintenance dose in a Thai population.
