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Irish Journal of Medical Science (1971 -)

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01.06.2014 | Original Article

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

verfasst von: N. S. Bazan, N. A. Sabry, A. Rizk, S. Mokhtar, O. A. Badary

Erschienen in: Irish Journal of Medical Science (1971 -) | Ausgabe 2/2014

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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.

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Titel: Factors affecting warfarin dose requirements and quality of anticoagulation in adult Egyptian patients: role of gene polymorphism
verfasst von: N. S. Bazan
N. A. Sabry
A. Rizk
S. Mokhtar
O. A. Badary
Publikationsdatum: 01.06.2014
Verlag: Springer London
Erschienen in: Irish Journal of Medical Science (1971 -) / Ausgabe 2/2014
Print ISSN: 0021-1265
Elektronische ISSN: 1863-4362
DOI: https://doi.org/10.1007/s11845-013-0978-y

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