Thiopurine S-methyltransferase polymorphisms and thiopurine toxicity in treatment of inflammatory bowel disease

World J Gastroenterol. 2010 Jul 7;16(25):3187-95. doi: 10.3748/wjg.v16.i25.3187.

Abstract

Aim: To evaluate the relationship between thiopurine S-methyltransferase (TPMT) polymorphisms and thiopurine-induced adverse drug reactions (ADRs) in inflammatory bowel disease (IBD).

Methods: Eligible articles that compared the frequency of TPMT polymorphisms among thiopurine-tolerant and -intolerant adult IBD patients were included. Statistical analysis was performed with Review Manager 5.0. Sub-analysis/sensitivity analysis was also performed.

Results: Nine studies that investigated a total of 1309 participants met our inclusion criteria. The incidence of TPMT gene mutation was increased 2.93-fold (95% CI: 1.68-5.09, P = 0.0001) and 5.93-fold (95% CI: 2.96-11.88, P < 0.00001), respectively, in IBD patients with thiopurine-induced overall ADRs and bone marrow toxicity (BMT), compared with controls. The OR for TPMT gene mutation in IBD patients with thiopurine-induced hepatotoxicity and pancreatitis was 1.51 (95% CI: 0.54-4.19, P = 0.43) and 1.02 (95% CI: 0.26-3.99, P = 0.98) vs controls, respectively.

Conclusion: This meta-analysis suggests that the TPMT polymorphisms are associated with thiopurine-induced overall ADRs and BMT, but not with hepatotoxicity and pancreatitis.

Publication types

  • Meta-Analysis
  • Review

MeSH terms

  • Adult
  • Azathioprine* / adverse effects
  • Azathioprine* / therapeutic use
  • Databases, Factual
  • Drug-Related Side Effects and Adverse Reactions*
  • Humans
  • Immunosuppressive Agents* / adverse effects
  • Immunosuppressive Agents* / therapeutic use
  • Inflammatory Bowel Diseases* / drug therapy
  • Inflammatory Bowel Diseases* / genetics
  • Mercaptopurine* / adverse effects
  • Mercaptopurine* / therapeutic use
  • Methyltransferases / genetics*
  • Polymorphism, Genetic*

Substances

  • Immunosuppressive Agents
  • Mercaptopurine
  • Methyltransferases
  • thiopurine methyltransferase
  • Azathioprine