VKORC1 and CYP2C9 polymorphisms are associated with warfarin dose requirements in Turkish patients
European Journal of Clinical Pharmacology, cilt.64, sa.9, ss.889-894, 2008 (SCI-Expanded, Scopus)
- Yayın Türü: Makale / Tam Makale
- Cilt numarası: 64 Sayı: 9
- Basım Tarihi: 2008
- Doi Numarası: 10.1007/s00228-008-0507-5
- Dergi Adı: European Journal of Clinical Pharmacology
- Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus
- Sayfa Sayıları: ss.889-894
- Anahtar Kelimeler: warfarin, dose, polymorphism, genotype, pharmacogenetics
- Sağlık Bilimleri Üniversitesi Adresli: Evet
Özet
Objectives: The objective of this study was to determine the quantitative influence of vitamin K epoxide reductase complex subunit 1 (VKORC1) and cytochrome P450 2C9 (CYP 2C9) polymorphisms on warfarin dose requirements in Turkish patients. Methods: A total of 205 patients taking warfarin for >2 months were enrolled in the study. Deoxyribonucleic acid (DNA) samples from these patients were genotyped for polymorphisms in VKORC1 and CYP2C9 genes. A linear regression analysis was used to determine the independent effects of genetic and non-genetic factors on mean warfarin dose requirements. Results: The VKORC1 promoter polymorphism (3673 G>A) was associated with differences in weekly mean varfarin dose: for GG genotype the dose was 43.18 mg/week, for GA genotype 33.78 mg/week and for AA genoype 25.83 mg/week (P<0.0001). Patients who carried VKORC1 and CYP2C9 variants needed a 40% lower mean weekly warfarin dose compared to wild types. Variables associated with lower warfarin dose requirements were VKORC1 3673 AA or GA genotype (both P<0.0001), one or two CYP2C9 variant alleles (both P<0.0001), increasing age (P<0.0001) and non-indication of venous thromboembolism for warfarin therapy (P=0.002). Conclusion: Polymorphisms in VKORC1 and CYP2C9 genes were important determinants of warfarin dose requirements in Turkish patients. © 2008 Springer-Verlag.