Effect of VKORC1 and CYP2C9 polymorphisms on warfarin dose requirement in Bangladeshi population

Warfarin, an oral anticoagulant is one of the most widely prescribed drugs in modern medicine. Large inter-individuals variability due to age, gender, diet, concurrent drug interactions and variations in CYP2C9 and VKORC1 genes make the management of warfarin therapy challenging and yet no study has been conducted on the Bangladeshi population. The aim of the study was to identify the role of VKORC1 and CYP2C9 polymorphisms in Bangladeshi population in dose requirement of warfarin. We studied 87 heart valve replacement patients who were prescribed warfarin for minimum of 6 months with a target International normalized ratio of 2.0-3.5. Genotyping of VKORC1rs9923231 (-1639 G>A), CYP2C9*2 and CYP2C9*3 was performed by Polymerase Chain Reaction- Restriction Fragment Length Polymorphism. The frequencies of GG, AG and AA genotypes of VKORC1rs9923231 in the studied population were 87.4%, 8%, and 4.6% respectively whereas the frequencies of the CYP2C9*1/3 and CYP2C9*3/3 were 4.6% and 3.4% respectively. The CYP2C9*2 was not found in the studied population. The results of this study indicate that comparatively higher daily maintenance doses of warfarin were required to achieve the target INR for patients carrying both GG genotype of VKORC1rs9923231 and wild type variant of CYP2C9*3 whereas minimum dose were required for patient having AA genotype of VKORC1rs9923231 and *3/*3 variant of CYP2C9.