SHORT COMMUNICATIONSCharacterization of a novel CYP2C9 gene mutation and structural bioinformatic protein analysis in a warfarin hypersensitive patientCiccacci, Cinzia; Falconi, Mattia; Paolillo, Nicoletta; Oteri, Francesco; Forte, Vittorio; Novelli, Giuseppe; Desideri, Alessandro; Borgiani, Paola Author Information aDepartment of Biopathology and Diagnostic Imaging, Section of Genetics, School of Medicine bDepartment of Biology and CIBB, Center of Biostatistics and Bioinformatics, University of Rome ‘Tor Vergata’ cCenter of Haemostasis and Thrombosis, Azienda Policlinico Tor Vergata dFondazione ‘Livio Patrizi’, Rome, Italy Correspondence to Paola Borgiani, PhD, Department of Biopathology and Diagnostic Imaging, Section of Medical Genetics, School of Medicine, Tor Vergata University, Via Montpellier1, Rome 00133, Italy Tel: +39 6 72596079; fax: +39 6 20900669; e-mail: [email protected] Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's Website (www.pharmacogeneticsandgenomics.com). Received November 25, 2010 Accepted January 18, 2011 Pharmacogenetics and Genomics 21(6):p 344-346, June 2011. | DOI: 10.1097/FPC.0b013e328344c340 Buy SDC Metrics AbstractIn Brief Warfarin (coumadin) is a worldwide-prescribed anticoagulant for the long-term treatment and prevention of thromboembolic events, presenting a great interindividual variability in the required dose. It is known that both environmental and genetic factors influence the dose necessary for the therapeutic effect. Herein we describe a pharmacogenetic study conducted on an Italian patient with warfarin hypersensitivity, who required a very low dosage to achieve therapeutic anticoagulation effect. We genotyped common polymorphisms in VKORC1, CYP2C9, and CYP4F2 genes, known to be involved in warfarin dosing. As the patient resulted in a mixture of low-dosing and high-dosing polymorphic variants, we searched for rare mutations by direct sequencing of the same genes. We identified in the CYP2C9 gene, a novel mutation in heterozygote status, c.374G>T, which produces the Arg125Leu substitution. We have observed, through an electrostatic analysis, that the new mutation produces an electrostatic alteration on the cytochrome surface. Supplemental Digital Content is available in the article. Copyright © 2011 Wolters Kluwer Health, Inc. All rights reserved.