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Irish Journal of Medical Science

, Volume 183, Issue 2, pp 161–172 | Cite as

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

  • N. S. BazanEmail author
  • N. A. Sabry
  • A. Rizk
  • S. Mokhtar
  • O. A. Badary
Original Article

Abstract

Background

Warfarin is the mainstay of anticoagulation therapy worldwide. CYP2C9 and VKORC1 are two major genetic factors associated with inter-individual and inter-ethnic 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.

Keywords

Pharmacogenetics Warfarin Allele frequency Race Genotyping Egyptians 

Notes

Acknowledgments

We express our deep appreciation and thankfulness to the Critical Care Medicine Department, Cairo University Hospitals and all its members for all the help and support. The authors thank Walid Salah at Analysis, Cairo, Egypt for his laboratory assistance.

Conflict of interest

We declare that there is no conflict of interest on this research study.

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Copyright information

© Royal Academy of Medicine in Ireland 2013

Authors and Affiliations

  • N. S. Bazan
    • 1
    Email author
  • N. A. Sabry
    • 2
  • A. Rizk
    • 3
  • S. Mokhtar
    • 3
  • O. A. Badary
    • 4
  1. 1.Critical Care Medicine DepartmentCairo University HospitalsCairoEgypt
  2. 2.Clinical Pharmacy DepartmentFaculty of Pharmacy, Cairo UniversityCairoEgypt
  3. 3.Critical Care Medicine DepartmentFaculty of Medicine, Cairo UniversityCairoEgypt
  4. 4.Clinical Pharmacy DepartmentFaculty of Pharmacy, Ain Shams UniversityCairoEgypt

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