Journal
EUROPEAN JOURNAL OF CLINICAL PHARMACOLOGY
Volume 64, Issue 9, Pages 889-894Publisher
SPRINGER HEIDELBERG
DOI: 10.1007/s00228-008-0507-5
Keywords
warfarin; dose; polymorphism; genotype; pharmacogenetics
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Funding
- Istanbul University, Turkey
- University of Florida Center for Pharmacogenomics
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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.
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