Pharmacogenetics of azathioprine in inflammatory bowel disease: a role for glutathione-S-transferase?
Article Details
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Stocco G, Pelin M, Franca R, De Iudicibus S, Cuzzoni E, Favretto D, Martelossi S, Ventura A, Decorti G
Pharmacogenetics of azathioprine in inflammatory bowel disease: a role for glutathione-S-transferase?
World J Gastroenterol. 2014 Apr 7;20(13):3534-41. doi: 10.3748/wjg.v20.i13.3534.
- PubMed ID
- 24707136 [ View in PubMed]
- 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.
DrugBank Data that Cites this Article
- Drug Enzymes
Drug Enzyme Kind Organism Pharmacological Action Actions Azathioprine Glutathione S-transferase A1 Protein Humans UnknownSubstrateDetails Azathioprine Glutathione S-transferase A2 Protein Humans UnknownSubstrateDetails Azathioprine Glutathione S-transferase Mu 1 Protein Humans UnknownSubstrateDetails Azathioprine GMP synthase [glutamine-hydrolyzing] Protein Humans UnknownSubstrateDetails Azathioprine Inosine triphosphate pyrophosphatase Protein Humans UnknownSubstrateDetails Azathioprine Inosine-5'-monophosphate dehydrogenase 1 Protein Humans UnknownSubstrateDetails Azathioprine Inosine-5'-monophosphate dehydrogenase 2 Protein Humans UnknownSubstrateDetails Azathioprine Nucleotide triphosphate diphosphatase NUDT15 Protein Humans UnknownSubstrateDetails - Drug Reactions
Reaction Details
