"Factors affecting warfarin dose requirements and quality of anticoagul" by N. S. Bazan, N. A. Sabry et al.
 

Factors affecting warfarin dose requirements and quality of anticoagulation in adult Egyptian patients: Role of gene polymorphism

Document Type

Article

Publication Date

1-1-2014

Abstract

Background: Warfarin is the mainstay of anticoagulation therapy worldwide. CYP2C9 and VKORC1 are two major genetic factors associated with inter-individual and interethnic variability in the warfarin dose. Aim: This study aims to assess the impact of VKORC1-1639G>A polymorphism and the most common CYP2C9 variant alleles (*2 and*3) on warfarin response in Egyptian patients. Methods: Genetic analysis of VKORC1-1639G>A and CYP2C9*2, CYP2C9*3 was performed using real-time PCR system. Patients maintained on a constant dose targeting an international normalized ratio range of 2-3.5 for at least three consecutive times were considered as good candidates. A stepwise linear regression analysis was used to determine the independent effects of genetic and non-genetic factors on daily warfarin dose requirements. Results: Patients carrying VKORC1 and CYP2C9 variant genotypes needed a 44.8% lower mean daily warfarin dose as compared to wild types. Patients with G allele for VKORC1-1639G>A had a significantly higher number of thromboembolic complications per month during therapy. On the first 30 days of therapy, presence of a variant allele either in VKORC1 or in CYP2C9 was associated with increased time required to achieve stable dosing. Multiple regression analysis showed that, VKORC1-1639G>A, age, CYP2C9*3, and smoking status explained 43.4% of the overall variability in the warfarin dose. Conclusion: VKORC1-1639G>A and CYP2C9 polymorphisms contribute to the difference in warfarin dose requirements and quality of anticoagulation amongst Egyptian patients. Study results support using personalized warfarin treatment in Egyptian patients. © Royal Academy of Medicine in Ireland 2013.

This document is currently not available here.

Share

COinS