Cytochrome-P450 2C9 Polymorphisms: Contribution to Warfarin Sensitivity and Prevalence in Egyptian Population

Hassouna, Amira; Hefnawy, Engy; El Shafie, Sahar; Zein ElDin, Maged

doi:10.21608/besps.2006.37542

Cytochrome-P450 2C9 Polymorphisms: Contribution to Warfarin Sensitivity and Prevalence in Egyptian Population

Document Type : Original Article

Authors

¹ Medical Biochemistry Department, Faculty of Medicine, Cairo University

² Surgery Department, Faculty of Medicine, Cairo University

³ Department of Human Genetics, Medical Research Institute, Alexandria University

10.21608/besps.2006.37542

Abstract

Cytochrome P450 2C9 is the main enzyme for degradation of many drugs including
the most widely prescribed oral anticoagulant; warfarin. It is polymorphic with three
common allelic variants: The wild type CYP2C9*1(the most active), and CYP2C9*2
and CYP2C9*3 both have less catalytic activity . The distribution of CYP2C9 variants
varies greatly from one population to another. The aim of the present study was to
assess the contribution of CYP2C9 polymorphims in the dose requirement of warfarin
in Egyptian population and to estimate the prevalence of different CYP2C9 alleles
and genotypes in the Egyptian population. One hundred and ninety six patients on
warfarin therapy (INR target between 2.0 and 3.0) and 150 normal subjects were
included in the present study. The genotypes were determined using PCR-RFLP.
Results: Allele frequencies in the Egyptian population sample were 70%, 20.1% and
9.9% for CYP2C9*1, CYP2C9*2 and CYP2C9*3 respectively. Cases carrying either
CYP2C9*2 or CYP2C9*3 required lower doses of warfarin for proper therapeutic
response than those with the wild allele. Conclusion: There is high frequency of
CYP2C9*2 and CYP2C9*3 variants amoung Egyptian population. These two variants
are related to lower warfarin dose requirements which may lead to over
anticoagulation and unstable anticoagulant response.

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