Characterization of a novel CYP2C9 gene mutation and structural bioinformatic protein analysis in a warfarin hypersensitive patient

Cinzia Ciccacci, Mattia Falconi, Nicoletta Paolillo, Francesco Oteri, Vittorio Forte, Giuseppe Novelli, Alessandro Desideri, Paola Borgiani

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish
Pages (from-to)344-346
Number of pages3
JournalPharmacogenetics and Genomics
Volume21
Issue number6
DOIs
Publication statusPublished - Jun 2011

Keywords

  • CYP2C9
  • mutation
  • pharmacogenetics
  • single nucleotide polymorphisms
  • warfarin

ASJC Scopus subject areas

  • Genetics
  • Molecular Biology
  • Molecular Medicine
  • Genetics(clinical)

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