Cytochrome-P450 2C9 Polymorphisms: Contribution to Warfarin Sensitivity and Prevalence in Egyptian Population | ||||
Bulletin of Egyptian Society for Physiological Sciences | ||||
Article 12, Volume 26, Issue 2, December 2006, Page 177-194 PDF (413.36 K) | ||||
Document Type: Original Article | ||||
DOI: 10.21608/besps.2006.37542 | ||||
View on SCiNiTO | ||||
Authors | ||||
Amira Hassouna* 1; Engy Hefnawy2; Sahar El Shafie3; Maged Zein ElDin3 | ||||
1Medical Biochemistry Department, Faculty of Medicine, Cairo University | ||||
2Surgery Department, Faculty of Medicine, Cairo University | ||||
3Department of Human Genetics, Medical Research Institute, Alexandria University | ||||
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. | ||||
Keywords | ||||
Cytochrome P450; Polymorphism; oral anticoagulation; pharmacogenetics | ||||
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