Pharmacogenetics of azathioprine in inflammatory bowel disease: A role for glutathione-S-transferase?

Gabriele Stocco, Marco Pelin, Raffaella Franca, Sara De Iudicibus, Eva Cuzzoni, Diego Favretto, Stefano Martelossi, Alessandro Ventura, Giuliana Decorti

Research output: Contribution to journalArticlepeer-review

Abstract

Azathioprine is a purine antimetabolite drug commonly used to treat inflammatory bowel disease (IBD). In vivo it is active after reaction with reduced glutathione (GSH) and conversion to mercaptopurine. Although this reaction may occur spontaneously, the presence of isoforms M and A of the enzyme glutathione-S-transferase (GST) may increase its speed. Indeed, in pediatric patients with IBD, deletion of GST-M1, which determines reduced enzymatic activity, was recently associated with reduced sensitivity to azathioprine and reduced production of azathioprine active metabolites. In addition to increase the activation of azathioprine to mercaptopurine, GSTs may contribute to azathioprine effects even by modulating GSH consumption, oxidative stress and apoptosis. Therefore, genetic polymorphisms in genes for GSTs may be useful to predict response to azathioprine even if more in vitro and clinical validation studies are needed.

Original languageEnglish
Pages (from-to)3534-3541
Number of pages8
JournalWorld Journal of Gastroenterology
Volume20
Issue number13
DOIs
Publication statusPublished - Apr 7 2014

Keywords

  • Azathioprine
  • Glutathione-S-transferase
  • Inflammatory bowel disease
  • Pediatric patients
  • Pharmacogenetics

ASJC Scopus subject areas

  • Gastroenterology
  • Medicine(all)

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