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Blood, 15 April 2004, Vol. 103, No. 8, pp. 3055-3057. Prepublished online as a Blood First Edition Paper on December 30, 2003; DOI 10.1182/blood-2003-07-2521. This Article Full Text (PDF) All Versions of this Article: 2003-07-2521v1 103/8/3055    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 Takahashi, H. Articles by Echizen, H. Search for Related Content PubMed PubMed Citation Articles by Takahashi, H. Articles by Echizen, H. Social Bookmarking                   What's this? Submitted July 30, 2003 Accepted November 17, 2003 5'-Flanking region polymorphisms of CYP2C9 and their relationship to S-warfarin metabolism in Caucasian and Japanese patients Harumi Takahashi, Ichiro Ieiri, Grant R Wilkinson, Gail Mayo, Toshitaka Kashima, Sosuke Kimura, Kenji Otsubo, and Hirotoshi Echizen* Department of Pharmacotherapy, Meiji Pharmaceutical University, Tokyo, Japan Department of Hospital Pharmacy, Tottori University, Tottori, Japan Department of Clinical Pharmacology, Vanderbilt University, Nashville, TN, USA Department of Cardiovascular Surgery, International Medical Center of Japan, Tokyo, Japan * Corresponding author; email: echizen{at}my-pharm.ac.jp. Caucasian and Japanese patients require different warfarin dosages to achieve therapeutic anticoagulation, but this can only be partly explained by genetic variability in the coding region of CYP2C9-a critical enzyme in the drug's metabolism. Accordingly, analysis of the -2.1kb 5'-flanking region of CYP2C9 was undertaken in 22 Caucasian and 38 Japanese patients whose unbound oral clearance of S-warfarin had been previously determined. Thirteen SNPs were identified, some of which were in linkage disequilibrium with functionally defective coding region variants. Those 5'-flanking patterns linked with at least one CYP2C9*3 allele or CYP2C9*2/*3 were associated with reduced CYP2C9 activity and warfarin dose. Japanese patients possessing the wild-type promoter and coding sequences had significantly (p<0.01) greater CYP2C9 activity than the Caucasians with the corresponding genotype. In conclusion, either unidentified polymorphisms further upstream in the promoter region or environmental factor(s) account for the differences in the warfarin doses between Caucasians and Japanese. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: S-Y Lee The type of the patient should be considered on discontinuation of anticoagulant and antiplatelet therapy Gut, January 1, 2009; 58(1): 153 - 154. [Full Text] [PDF] M. A. Kramer, A. E. Rettie, M. J. Rieder, E. T. Cabacungan, and R. N. Hines Novel CYP2C9 Promoter Variants and Assessment of Their Impact on Gene Expression Mol. Pharmacol., June 1, 2008; 73(6): 1751 - 1760. [Abstract] [Full Text] [PDF] T. C. DeLozier, S.-C. Lee, S. J. Coulter, B. C. Goh, and J. A. Goldstein Functional Characterization of Novel Allelic Variants of CYP2C9 Recently Discovered in Southeast Asians J. Pharmacol. Exp. Ther., December 1, 2005; 315(3): 1085 - 1090. [Abstract] [Full Text] [PDF] R. R Shah Pharmacogenetics in drug regulation: promise, potential and pitfalls Phil Trans R Soc B, August 29, 2005; 360(1460): 1617 - 1638. [Abstract] [Full Text] [PDF]

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