Mutation in the ITPA gene predicts intolerance to azathioprine

Nucleosides Nucleotides Nucleic Acids. 2004 Oct;23(8-9):1393-7. doi: 10.1081/NCN-200027639.

Abstract

Inosine triphosphate pyrophosphatase (ITPase) deficiency occurs with polymorphic frequencies in Caucasians and results in the benign accumulation of the inosine nucleotide ITP. In 62 patients treated with azathioprine for inflammatory bowel disease, the ITPA 94C>A deficiency-associated allele was significantly associated with adverse drug reactions (OR 4.2, 95% CI 1.6-11.5, p = 0.0034). Significant associations were found for flu-like symptoms (OR 4.7, 95% CI 1.2-18.1, p = 0.0308), rash (OR 10.3, 95% CI 4.7-62.9, p = 0.0213) and pancreatitis (OR 6.2, CI 1.1-32.6, p = 0.0485). Polymorphism in the ITPA gene thus predicts AZA intolerance. Alternative immunosuppressive drugs, particularly 6-thioguanine, should be considered for AZA-intolerant patients with ITPase deficiency.

MeSH terms

  • Alleles
  • Antimetabolites, Antineoplastic / pharmacology
  • Azathioprine / pharmacology*
  • Cohort Studies
  • Drug Resistance, Neoplasm*
  • Genotype
  • Heterozygote
  • Humans
  • Immunosuppressive Agents / pharmacology
  • Inflammatory Bowel Diseases / drug therapy*
  • Inosine Triphosphatase
  • Mutation*
  • Odds Ratio
  • Phenotype
  • Polymorphism, Genetic
  • Pyrophosphatases / genetics*
  • Retrospective Studies
  • Thioguanine / pharmacology

Substances

  • Antimetabolites, Antineoplastic
  • Immunosuppressive Agents
  • Pyrophosphatases
  • Thioguanine
  • Azathioprine