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

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.