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

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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.

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