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


CONCLUSIONS
This meta-analysis suggests that the TPMT polymorphisms are associated with thiopurine-induced overall ADRs and BMT, but not with hepatotoxicity and pancreatitis.
Dong
Xian-Wen
XW
Department of Gastroenterology, Renji Hospital, Shanghai Institute of Digestive Disease, Shanghai Jiao Tong University, School of Medicine, Shanghai 200001, China.
Zheng
Qing
Q
Zhu
Ming-Ming
MM
Tong
Jing-Lu
JL
Ran
Zhi-Hua
ZH
D000328:Adult; D001379:Azathioprine / Q000009:adverse effects / Q000627:therapeutic use; D016208:Databases, Factual; D064420:Drug-Related Side Effects and Adverse Reactions; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000627:therapeutic use; D015212:Inflammatory Bowel Diseases / Q000188:drug therapy / Q000235:genetics; D015122:Mercaptopurine / Q000009:adverse effects / Q000627:therapeutic use; D008780:Methyltransferases / Q000235:genetics*; D011110:Polymorphism, Genetic
D007166:Immunosuppressive Agents; D015122:Mercaptopurine; D008780:Methyltransferases; C022745:thiopurine methyltransferase; D001379:Azathioprine