The impact of CYP2C9 and VKORC1 genetic polymorphism and patient characteristics upon warfarin dose requirements in an adult Turkish population

• Published in: Heart and vessels 2010-03, Vol.25 (2), p.155-162
• Main Authors: Ozer, Nihat, Cam, Nese, Tangurek, Burak, Ozer, Songul, Uyarel, Huseyin, Oz, Dilaver, Guney, Mehmet Rasit, Ciloglu, Figen
• Format: Article
• Language: English
• Subjects: Adult; Age Factors; Aged; Anticoagulants - administration & dosage; Anticoagulants - pharmacokinetics; Aryl Hydrocarbon Hydroxylases - genetics; Aryl Hydrocarbon Hydroxylases - metabolism; Biomedical Engineering and Bioengineering; Blood Coagulation - drug effects; Body Surface Area; Cardiac Surgery; Cardiology; Chi-Square Distribution; Cytochrome P-450 CYP2C9; Drug Dosage Calculations; Drug Monitoring; Female; Gene Frequency; Genetics; Genotype; Genotype & phenotype; Humans; International Normalized Ratio; Male; Medicine; Medicine & Public Health; Middle Aged; Mixed Function Oxygenases - genetics; Mixed Function Oxygenases - metabolism; Original Article; Patients; Phenotype; Polymorphism; Polymorphism, Genetic; Regression Analysis; Risk Assessment; Risk Factors; Turkey; Vascular Surgery; Vitamin K Epoxide Reductases; Warfarin - administration & dosage; Warfarin - pharmacokinetics; Young Adult
• ISSN: 0910-8327; 1615-2573
• DOI: 10.1007/s00380-009-1177-7

In this study, we investigated the contribution of vitamin K epoxide reductase ( VKORC1 ) and cytochrome P450 2C9 ( CYP2C9 ) genotypes, age, and body surface area (BSA) on warfarin dose requirements and in an adult Turkish population. Blood samples were collected from 100 Turkish patients with stable warfarin dose requirements and an international normalized ratio (INR) of the prothrombin time within the therapeutic range. Genetic analyses for CYP2C9 genotypes ( *2 and *3 alleles) and VKORC1 −1639 G>A polymorphism were performed and venous INR determined. The mean warfarin daily dose requirement was higher in CYP2C9 homozygous wild-type patients, compared to those with the variant *3 allele ( P < 0.05), similar to those with the variant *2 allele ( P > 0.05) and highest in patients with the VKORC1 −1639 GG genotype compared to those with the GA genotype and the AA genotype ( P < 0.01). The time to therapeutic INR was longer in CYP2C9 homozygous wild-type patients compared with those with the variant *2 and *3 alleles ( P < 0.01), and longer in patients with the VKORC1 (position −1639) GG genotype compared with those with the GA genotype and the AA genotype ( P < 0.01). The multivariate regression model including the variables of age ( R 2 = 4.4%), BSA ( R 2 = 27.4%), CYP2C9 ( R 2 = 8.1%), and VKORC1 genotype ( R 2 = 34.1%) produced the best model for estimating warfarin dose ( R 2 = 60.4%). VKORC1 genotype and CYP2C9 polymorphism affect daily dose requirements and time to therapeutic INR in Turkish patients receiving warfarin for anticoagulation.