학술논문
Effect of VKORCL and CYP2C9 polymorphisms on warfarin dose requirement in Bangladeshi population
vitamin K epoxide reductase complex 1
vitamin K epoxide reductase complex 1
Document Type
Report
Author
Source
Pakistan Journal of Pharmaceutical Sciences. March 2017, Vol. 30 Issue 2, p341, 6 p.
Subject
Language
English
ISSN
1011-601X
Abstract
INTRODUCTION Warfarin is the most commonly prescribed oral anticoagulant for the treatment and prevention of thrombotic diseases such as myocardial infarction, ischemic stroke, atrial fibrillation, deep vein thrombosis (Daly, 2014; [...]
Warfarin, an oral anticoagulant is one of the most widely prescribed drugs in modern medicine. Large interindividuals variability due to age, gender, diet, concurrent drug interactions and variations in CYP2C9 and VKORCl 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 VKORCl 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 VKORC1 rs9923231 (-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 VKORC lrs9923231 in the studied population were 87.4%, 8%, and 4.6% respectively whereas the frequencies of the CYP2C9*l/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 VKORClrs9923231 and wild type variant of CYP2C9*3 whereas minimum dose were required for patient having AA genotype of VKORC lrs9923231 and *3/*3 variant of CYP2C9. Keywords: VKORCI, CYP2C9, polymorphism, warfarin dose adjustment, Bangladeshi population.
Warfarin, an oral anticoagulant is one of the most widely prescribed drugs in modern medicine. Large interindividuals variability due to age, gender, diet, concurrent drug interactions and variations in CYP2C9 and VKORCl 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 VKORCl 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 VKORC1 rs9923231 (-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 VKORC lrs9923231 in the studied population were 87.4%, 8%, and 4.6% respectively whereas the frequencies of the CYP2C9*l/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 VKORClrs9923231 and wild type variant of CYP2C9*3 whereas minimum dose were required for patient having AA genotype of VKORC lrs9923231 and *3/*3 variant of CYP2C9. Keywords: VKORCI, CYP2C9, polymorphism, warfarin dose adjustment, Bangladeshi population.