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Blood, 1 April 2004, Vol. 103, No. 7, pp. 2630-2635. Prepublished online as a Blood First Edition Paper on December 4, 2003; DOI 10.1182/blood-2003-09-3043. This Article Full Text Full Text (PDF) All Versions of this Article: 2003-09-3043v1 103/7/2630    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map 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 Shikata, E. Articles by Otsubo, K. Search for Related Content PubMed PubMed Citation Articles by Shikata, E. Articles by Otsubo, K. Related Collections Hemostasis, Thrombosis, and Vascular Biology Related Article in Blood Online Related Letter in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY Association of pharmacokinetic (CYP2C9) and pharmacodynamic (factors II, VII, IX, and X; proteins S and C; and -glutamyl carboxylase) gene variants with warfarin sensitivity Eriko Shikata, Ichiro Ieiri, Shingo Ishiguro, Hironao Aono, Kazuko Inoue, Tomoko Koide, Shigetsugu Ohgi, and Kenji Otsubo From the Department of Hospital Pharmacy; and the Department of Second Surgery, Faculty of Medicine, Tottori University, Yonago, Japan. We analyzed mutations of 7 vitamin K—dependent protein and cytochrome P450 2C9 genes in 45 patients and investigated whether any contribute to the large interpatient variability in the warfarin dose-effect relationship. Total clearance and daily dose, INR and INR/Cp, were used as pharmacokinetic and pharmacodynamic indexes, respectively. Patients were grouped by genotype based on a single polymorphism and combinations of polymorphisms. Among the 30 sequence variants identified, CYP2C9*3, 165Thr Met of the factor II gene, -402G A, (37-bp repeat)n, and -746T C of the factor VII gene, and (CAA repeat)n of the -glutamyl carboxylase gene were selected as candidate polymorphisms. As the analysis of single polymorphisms implied, the highest INR/Cp mean values and the lowest warfarin maintenance doses were observed in patients homozygous for the 165Met, -402G, (37-bp repeat)6 and -746T alleles. Multiple regression analysis revealed that warfarin sensitivity was independently associated with -402G A, (CAA repeat)n, CYP2C9*3, and 165Thr Met, which accounted for 50% of variance. These results suggest that part of the considerable interpatient variation is attributable to genetic variation, and the combined genotyping of CYP2C9 and certain vitamin K—dependent protein genes is useful for predicting anticoagulant responses. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: Wobbling with warfarin Bruce Furie Blood 2004 103: 2437. [Full Text] [PDF] Related Letter in Blood Online: Gamma-glutamyl carboxylase (GGCX) microsatellite and warfarin dosing Leslie Y. Chen, Niclas Eriksson, Rhian Gwilliam, David Bentley, Panos Deloukas, and Mia Wadelius Blood 2005 106: 3673-3674. [Full Text] [PDF] This article has been cited by other articles: M.-J. Kim, S.-M. Huang, U. A. Meyer, A. Rahman, and L. J. Lesko A Regulatory Science Perspective on Warfarin Therapy: A Pharmacogenetic Opportunity J. Clin. Pharmacol., February 1, 2009; 49(2): 138 - 146. [Abstract] [Full Text] [PDF] M. Wadelius, L. Y. Chen, J. D. 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