Frequencies of Polymorphism Associated with Cytochrome P450 2C9 in Thais

Abstract

Abstract:

Background: The use of warfarin for prevention and treatment of thromboembolic disorder
is complicated by unpredictable dose response, partly attributed to polymorphisms of the CYP2C9
which can alter catalytic properties and increase anticoagulant effect. This study aims to determine
the frequencies of CYP2C9 polymorphisms in Thai people and functional effects of CYP2C9 genotype
in responsible for warfarin dosage. Methods: Patients requiring warfarin therapy and healthy blood
donors were recruited. Warfarin dosage and clinical informations were collected. The CYP2C9 genotype
was determined by standard PCR and RFLP. Results: The genotype of 326 blood donors and 67
patients were CYP2C9*1/CYP2C9*1; 91.4%, 91.1% and CYP2C9*1/CYP2C9*3; 8.6%, 8.9%, respectively.
There were no gender difference (p = 0.781). The mean warfarin dose (mean±SD) for patients who
had INR 2.0-3.0 was 27.8±12.7 mg/week. Patients with CYP2C9*1/CYP2C9*3 required a lower warfarin
doses (20.1±5.9 mg/week) compared to CYP2C9*1/CYP2C9*1 (28.7±13.0 mg/week) but there
was not statistically significant (p = 0.081). However, the mean warfarin dose was lower in elderly of
more than 60 years compared to those less than 60 years (p < 0.01). Conclusion: Frequencies of
CYP2C9 polymorphisms in Thais are mainly CYP2C9*1/CYP2C9*1 91.4% and CYP2C9*1/CYP2C9*3
8.6%, similar to previous studies in Asian people. The patients with CYP2C9*1/CYP2C9*3 tended to
receive lesser dose of warfarin than CYP2C9*1/CYP2C9*1 genotype.