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Blood, 15 January 2005, Vol. 105, No. 2, pp. 645-649. Prepublished online as a Blood First Edition Paper on September 9, 2004; DOI 10.1182/blood-2004-06-2111. This Article Full Text Full Text (PDF) All Versions of this Article: 2004-06-2111v1 105/2/645    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 D'Andrea, G. Articles by Margaglione, M. Search for Related Content PubMed PubMed Citation Articles by D'Andrea, G. Articles by Margaglione, M. Related Collections Hemostasis, Thrombosis, and Vascular Biology Clinical Trials and Observations Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY A polymorphism in the VKORC1 gene is associated with an interindividual variability in the dose-anticoagulant effect of warfarin Giovanna D'Andrea, Rosa Lucia D'Ambrosio, Pasquale Di Perna, Massimiliano Chetta, Rosa Santacroce, Vincenzo Brancaccio, Elvira Grandone, and Maurizio Margaglione From the Unita' di Aterosclerosi e Trombosi, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), "Casa Sollievo della Sofferenza," S. Giovanni Rotondo, Foggia; the Divisione di Ematologia, Unità di Coagulazione, Ospedale "A. Cardarelli," Napoli; and the Istituto di Genetica Medica, Dipartimento di Scienze Biomediche, Università di Foggia, Foggia, Italy. Patients require different warfarin dosages to achieve the target therapeutic anticoagulation. The variability is largely genetically determined, and it can be only partly explained by genetic variability in the cytochrome CYP2C9 locus. In 147 patients followed from the start of anticoagulation with warfarin, we have investigated whether VKORC1 gene mutations have affected doses of drug prescribed to acquire the target anticoagulation intensity. Two synonymous mutations, 129C>T at Cys43 and 3462C>T at Leu120, and 2 missense mutations, Asp38Tyr and Arg151Gln, were identified. None of these mutations was found to affect the interindividual variability of warfarin prescribed. Finally, 2 common polymorphisms were found, 1173C>T in the intron 1 and 3730G>A transition in the 3' untranslated region (UTR). Regardless of the presence of confounding variables, the mean adjusted dose required of warfarin was higher (6.2 mg) among patients with the VKORC1 1173CC genotype than those of patients carrying the CT (4.8 mg; P = .002) or the TT genotype (3.5 mg; P < .001). In the present setting, VKORC1 and CYP2C9 genetic variants investigated accounted for about a third (r2, 0.353) of the interindividual variability. Genetic variants of the VKORC1 gene locus modulate the mean daily dose of drug prescribed to acquire the target anticoagulation intensity. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: 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. Stricker A genome-wide association study of acenocoumarol maintenance dosage Hum. Mol. Genet., October 1, 2009; 18(19): 3758 - 3768. 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