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Related Collections Hemostasis, Thrombosis, and Vascular Biology Clinical Trials and Observations Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Blood, 1 September 2000, Vol. 96, No. 5, pp. 1816-1819 HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY Influence of cytochrome P-450 CYP2C9 polymorphisms on warfarin sensitivity and risk of over-anticoagulation in patients on long-term treatment Janis Taube, David Halsall, and Trevor Baglin From the Department of Haematology, Addenbrooke's NHS Trust, Cambridge, United Kingdom Cytochrome P-450 2C9 is the principle enzyme that terminates the anticoagulant effect of warfarin. Genetic polymorphisms in CYP2C9 producing variants with altered catalytic properties have been identified. Patients (n = 561) with a target international normalized ratio (INR) of 2.5 who had been treated with warfarin for more than 2 months were anonymously genotyped for the wild-type CYP2C9*1 allele and the 2C9*2 and 2C9*3 variants. The mean maintenance dose of warfarin in patients who were wild-type for both alleles was 5.01 mg. The maintenance dose of warfarin was significantly related to genotype (Kruskall-Wallis, 2 = 17.985, P = .001) with mean maintenance doses in patients with variant alleles between 61% and 86% of that in wild-type patients. The odds ratio for the 2C9*2 allele in patients with a maintenance dose of 1.5 mg or less was 5.42 (95% CI 1.68-17.4). The odds ratio for one or more variant alleles in patients developing an INR of 8.0 or greater was 1.52 (95% CI 0.64-3.58). The SD of the mean INR, percentage of high INRs, and person-time spent in range were determined as parameters of stability. There was no difference between patients grouped according to genotype for any parameter of stability. This study confirmed an association between CYP2C9 genotype and warfarin sensitivity. However, the possession of a variant allele does not increase the likelihood of severe over-anticoagulation or stability of anticoagulation during long-term therapy. © 2000 by The American Society of Hematology.   CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: F. Marin, R. Gonzalez-Conejero, P. Capranzano, T. A. Bass, V. Roldan, and D. J. Angiolillo Pharmacogenetics in cardiovascular antithrombotic therapy. J. Am. Coll. Cardiol., September 15, 2009; 54(12): 1041 - 1057. [Abstract] [Full Text] [PDF] M. H. Rosove and W. W. Grody Should We Be Applying Warfarin Pharmacogenetics to Clinical Practice? No, Not Now Ann Intern Med, August 18, 2009; 151(4): 270 - 273. 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