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Blood, 1 October 2005, Vol. 106, No. 7, pp. 2329-2333. Prepublished online as a Blood First Edition Paper on June 9, 2005; DOI 10.1182/blood-2005-03-1108. This Article Full Text (PDF) All Versions of this Article: 2005-03-1108v1 106/7/2329    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Sconce, E. A Articles by Kamali, F. Search for Related Content PubMed PubMed Citation Articles by Sconce, E. A Articles by Kamali, F. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted March 18, 2005 Accepted May 25, 2005 The impact of CYP2C9 and VKORC1 genetic polymorphism and patient characteristics upon warfarin dose requirements: proposal for a new dosing regimen Elizabeth A Sconce, Tayyaba I Khan, Hilary A Wynne, Peter Avery, Louise Monkhouse, Barry P King, Peter Wood, Patrick Kesteven, Ann K Daly, and Farhad Kamali* Schools of Clinical and Laboratory Sciences and Mathematics and Statistics, University of Newcastle, Newcastle upon Tyne, United Kingdom Care of the Elderly, Royal Victoria Infirmary, Newcastle upon Tyne, United Kingdom * Corresponding author; email: farhad.kamali{at}ncl.ac.uk. Current dosing algorithms do not account for genetic and environmental factors for warfarin dose determinations. This study investigated the contribution of age, CYP2C9 and VKORC1 genotype and body-size to warfarin dose requirements. 297 patients with stable anticoagulation with target International Normalised Ratio (INR) of 2.0-3.0, were studied. Genetic analyses for CYP2C9 (*2 and *3 alleles) and VKORC1 (-1639 and intron 1 polymorphisms) were performed and venous INR and plasma R- and S-warfarin concentrations determined. The mean warfarin daily dose requirement was highest in CYP2C9 homozygous wild-type patients, compared to those with the variant *2 and *3 alleles (p< 0.0001) and highest in patients with the VKORC1 (position-1639) GG genotype compared to those with the GA genotype and the AA genotype (p< 0.0001). Mean warfarin daily dose requirements fell by 0.5-0.7mg per decade between the ages of 20-90 years. Age, height and CYP2C9 genotype significantly contributed to S-warfarin and total warfarin clearance, whereas only age and body size significantly contributed to R-warfarin clearance. The multivariate regression model including the variables of age, CYP2C9 and VKORC1 genotype and height produced the best model for estimating warfarin dose (R2 = 55%). Based upon the data a new warfarin dosing regimen has been developed.The validity of the dosing regimen was confirmed in a second cohort of patients on warfarin therapy. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: T. P. Moyer, D. J. O'Kane, L. M. Baudhuin, C. L. Wiley, A. Fortini, P. K. Fisher, D. M. Dupras, R. Chaudhry, P. Thapa, A. R. Zinsmeister, et al. Warfarin Sensitivity Genotyping: A Review of the Literature and Summary of Patient Experience Mayo Clin. Proc., December 1, 2009; 84(12): 1079 - 1094. [Abstract] [Full Text] [PDF] M. Teichert, M. Eijgelsheim, F. Rivadeneira, A. G. Uitterlinden, R. H.N. van Schaik, A. Hofman, P. A.G.M. De Smet, T. van Gelder, L. E. Visser, and B. H.Ch. 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