Publication Date:
2012-09-22
Description:
Objectives The main aim of this study was to determine whether CYP2C9 and VKORC1 polymorphisms influence warfarin dose variability during initial dose-finding phase and during maintenance treatment after 360 days. Methods Two hundred and six consecutive patients who were beginning warfarin therapy were selected. They were assessed for general and clinical characteristics; prescribed warfarin dose; response to therapy on days 7–10, 30, 60, 180, and 360; adverse events; and CYP2C9 *2, *3, *5, *6, *8, *11, and VKORC1 1639G 〉A assays. Results During the first 30 days of anticoagulation, the relative variability of warfarin dose was significantly associated with CYP2C9*2 and CYP2C9*3 polymorphisms ( p = 0.02) and with VKORC1 1639G 〉A genotypes ( p = 0.04). Warfarin variability was also statistically different according to predicted metabolic phenotype and to VKORC1 genotypes after 360 days of treatment, and in the phase between 180 and 360 days (long-term dose variability). Both CYP2C9 and VKORC1 polymorphisms were associated with the international normalized ratio (INR) made between 7 and 10 days/initial dose ratio, adjusted for covariates ( p 〈 0.01 and p = 0.02, respectively). Patients carrying VKORC1 and CYP2C9 variants presented lower required dose (at the end of follow-up of 360 days) compared to patients carrying wild-type genotypes ( p = 0.04 and p = 0.03, respectively). Conclusions Genetic information on CYP2C9 and VKORC1 is important both for the initial dose-finding phase and during maintenance treatment with warfarin. Content Type Journal Article Category Pharmacogenetics Pages 1-9 DOI 10.1007/s00228-012-1404-5 Authors Paulo Caleb Junior Lima Santos, Laboratory of Genetics and Molecular Cardiology, Heart Institute (InCor), University of Sao Paulo Medical School, Av. Dr. Eneas de Carvalho Aguiar, 44 Cerqueira Cesar, Sao Paulo, SP CEP 05403-000, Brazil Carla Luana Dinardo, Laboratory of Genetics and Molecular Cardiology, Heart Institute (InCor), University of Sao Paulo Medical School, Av. Dr. Eneas de Carvalho Aguiar, 44 Cerqueira Cesar, Sao Paulo, SP CEP 05403-000, Brazil Isolmar Tadeu Schettert, Laboratory of Genetics and Molecular Cardiology, Heart Institute (InCor), University of Sao Paulo Medical School, Av. Dr. Eneas de Carvalho Aguiar, 44 Cerqueira Cesar, Sao Paulo, SP CEP 05403-000, Brazil Renata Alonso Gadi Soares, Laboratory of Genetics and Molecular Cardiology, Heart Institute (InCor), University of Sao Paulo Medical School, Av. Dr. Eneas de Carvalho Aguiar, 44 Cerqueira Cesar, Sao Paulo, SP CEP 05403-000, Brazil Liz Kawabata-Yoshihara, University Hospital of the University of Sao Paulo, Internal Medicine Division, Sao Paulo, Brazil Isabela Martins Bensenor, University Hospital of the University of Sao Paulo, Internal Medicine Division, Sao Paulo, Brazil José Eduardo Krieger, Laboratory of Genetics and Molecular Cardiology, Heart Institute (InCor), University of Sao Paulo Medical School, Av. Dr. Eneas de Carvalho Aguiar, 44 Cerqueira Cesar, Sao Paulo, SP CEP 05403-000, Brazil Paulo Andrade Lotufo, University Hospital of the University of Sao Paulo, Internal Medicine Division, Sao Paulo, Brazil Alexandre Costa Pereira, Laboratory of Genetics and Molecular Cardiology, Heart Institute (InCor), University of Sao Paulo Medical School, Av. Dr. Eneas de Carvalho Aguiar, 44 Cerqueira Cesar, Sao Paulo, SP CEP 05403-000, Brazil Journal European Journal of Clinical Pharmacology Online ISSN 1432-1041 Print ISSN 0031-6970
Print ISSN:
0031-6970
Electronic ISSN:
1432-1041
Topics:
Chemistry and Pharmacology
,
Medicine
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