Contribution of glutathione-s-transferases to the pharmacogenetics of azathioprine

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

Research output: Chapter in Book/Report/Conference proceedingChapter

Abstract

Azathioprine is a purine antimetabolite drug commonly used as immunomodulator in the treatment of various chronic inflammatory diseases, such as inflammatory bowel disease (IBD). Azathioprine is activated in vivo after reaction with reduced glutathione (GSH) and conversion to mercaptopurine. Although this reaction may occur spontaneously, the presence of the enzyme glutathione-S-transferase (GST), in particular of isoforms GST-A1/GST-A2 and GST-M1, can increase its speed, leading to a faster activation of azathioprine to active thioguanine nucleotides. Moreover, GSTs may contribute to azathioprine effects by modulating GSH consumption, oxidative stress and apoptosis. Indeed, in young patients with IBD, deletion of GST-M1, which determines reduced enzymatic activity, was recently associated with reduced sensitivity to azathioprine and reduced production of its active metabolites. 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
Title of host publicationGlutathione: Dietary Sources, Role in Cellular Functions and Therapeutic Effects
PublisherNova Science Publishers, Inc.
Pages69-84
Number of pages16
ISBN (Print)9781634634076, 9781634633727
Publication statusPublished - Jan 1 2015

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Keywords

  • Azathioprine
  • Glutathione-S-transferase
  • Inflammatory bowel disease
  • Oxidative stress
  • pharmacogenetics

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)

Cite this

Stocco, G., Pelin, M., Franca, R., Iudicibus, S. D., Cuzzoni, E., Favretto, D., Candussio, L., Martelossi, S., Ventura, A., & Decorti, G. (2015). Contribution of glutathione-s-transferases to the pharmacogenetics of azathioprine. In Glutathione: Dietary Sources, Role in Cellular Functions and Therapeutic Effects (pp. 69-84). Nova Science Publishers, Inc..