Effect of CYP2C9 AND VKORC1 genetic polymorphisms on warfarin dose requirement in south indian population.

ABSTRACT

Cytochrome P450 2C9 (CYP2C9) and vitamin K epoxide reductase complex subunit 1 (VKORC1) genetic polymorphisms were strongly associated with warfarin dose requirement in Caucasians, African Americans and other populations. Our aim was to evaluate the effect of CYP2C9 and VKORC1 genetic polymorphisms on warfarin dose requirement in south Indian population. A total of 150 patients on warfarin with stable INR (2- 3.5) for the past 3 months were recruited. The genotypes of CYP2C9*2 and *3 and VKORC1 -1639G>A were compared with mean daily warfarin dose (MDWD). The variant allele frequency of VKORC1 -1639G>A was found to be 10.4% and CYP2C9*2 and CYP2C9*3 were found to be 4.5% and 6.6%, respectively. Our study showed that the mean daily warfarin dose is higher in patients with wild type genotypes of CYP2C9 and VKORC1 compared to those with variant genotypes. Multivariate regression analysis revealed that age, body mass index (BMI), duration of therapy and genetic polymorphisms of CYP2C9 and VKORC1 together contribute to 36.1% variability in MDWD in south Indian population.