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Blood, 1 July 2005, Vol. 106, No. 1, pp. 135-140. Prepublished online as a Blood First Edition Paper on March 24, 2005; DOI 10.1182/blood-2005-01-0341. This Article Full Text Full Text (PDF) All Versions of this Article: 2005-01-0341v1 106/1/135    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 Bodin, L. Articles by Loriot, M.-A. Search for Related Content PubMed PubMed Citation Articles by Bodin, L. Articles by Loriot, M.-A. 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 Cytochrome P450 2C9 (CYP2C9) and vitamin K epoxide reductase (VKORC1) genotypes as determinants of acenocoumarol sensitivity Laurent Bodin, Céline Verstuyft, David-Alexandre Tregouet, Annie Robert, Liliane Dubert, Christian Funck-Brentano, Patrice Jaillon, Philippe Beaune, Pierre Laurent-Puig, Laurent Becquemont, and Marie-Anne Loriot From the Institut National de la Santé et de la Recherche Médicale (INSERM), Unité Mixte de Recherche Scientifique (UMRS) 490, University René Descartes, Paris, France; Assistance Publique Hôpitaux de Paris, Pharmacology Department, Bicêtre University Hospital, University Paris-Sud, Le Kremlin Bicêtre, France; Assistance Publique Hôpitaux de Paris, Pharmacology Department, Saint Antoine University Hospital–University Pierre et Marie Curie Paris 6, Paris, France; INSERM, U525, FacultédeMédecine, Hôpital Pitié-Salpétrière, Paris, France; the Department of Immunology and Hematology, Saint-Antoine Hospital, Paris, France; Clinical Investigation Center, Saint-Antoine Hospital, Paris, France; andAssistance Publique Hôpitaux de Paris, Biochemistry Department, European Georges Pompidou Hospital, Paris, France. The aim of the study is to explore the contribution of genetic factors related either to drug metabolism (cytochrome P450 2C9) or to drug target (vitamin K epoxide reductase) to variability in the response to acenocoumarol among 222 healthy volunteers after a single oral dose. Associations between a pharmacodynamic index (reduction in factor VII activity and international normalized ratio [INR] change) and several genetic polymorphisms (VKORC1: –4931T>C, –4451C>A, –2659G>C, –1877A>G, –1639G>A, 497C>G, 1173C>T, and CYP2C9*3) were investigated using haplotype and univariate analyses. VKORC1 haplotypes were associated with the pharmacologic response, and this association can be explained only by the effect of the –1639G>A polymorphism (or alternatively by 1173C>T, which is in complete association with it). Indeed, it explains about one third of the variability of the pharmacologic response (37% of factor VII decrease and 30% of INR change). Moreover, the previously observed effect of the CYP2C9*3 allele is independent of the VKORC1 gene effect. These 2 polymorphisms account for up to 50% of the interindividual variability. The simple genotyping of 2 single-nucleotide polymorphisms (SNPs), VKORC1 –1639G>A or 1173C>T and the CYP2C9*3 polymorphisms, could thus predict a high risk of overdose before initiation of anticoagulation with acenocoumarol, and provide a safer and more individualized anticoagulant therapy. 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. [Abstract] [Full Text] [PDF] F. Marin, R. Gonzalez-Conejero, P. Capranzano, T. A. Bass, V. 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