Genetic and Nongenetic Determinants of Variable Warfarin Dose Requirements: A Report from North India

Abstract

Introduction: Warfarin is widely used and will continue to be prescribed especially in developing countries due to its low cost. Given the huge patient load requiring anticoagulation, there is a need to develop strategies to optimize warfarin therapy for ensuring safe and effective anticoagulation. In the present work, we aimed at elucidating the association of genetic and nongenetic variables with warfarin dose requirement in patients attending the cardiovascular clinic in a tertiary care center of North India. Methods: This was a prospective study conducted over 1 year. Patient demographic and clinical details were captured in customized case record forms. Genotyping was done using the polymerase chain reaction-restriction fragment length polymorphism method. Pharmacogenetic influence of CYP2C9 (rs1799853 and rs1057910) and VKORC1 (rs9923231) variant alleles was studied. The association of genetic and nongenetic factors with warfarin dose was quantified using a stepwise multivariate linear regression model. Results: Two hundred and forty patients were screened. Data from 82 eligible patients were used for quantifying the association of genetic and nongenetic factors with warfarin dose. A descriptive model based on CYP2C9*3 (rs1057910) and VKORC1 (rs9923231) variant alleles and BMI was developed. The model explains nearly half of the interindividual variation in warfarin dose requirement. Conclusion: The model explains nearly half of the interindividual variation in warfarin dose in patients with atrial fibrillation and or requiring valve replacement.