Brief Article
Copyright ©2010 Baishideng. All rights reserved.
World J Gastroenterol. Jul 7, 2010; 16(25): 3187-3195
Published online Jul 7, 2010. doi: 10.3748/wjg.v16.i25.3187
Thiopurine S-methyltransferase polymorphisms and thiopurine toxicity in treatment of inflammatory bowel disease
Xian-Wen Dong, Qing Zheng, Ming-Ming Zhu, Jing-Lu Tong, Zhi-Hua Ran
Xian-Wen Dong, Qing Zheng, Ming-Ming Zhu, Jing-Lu Tong, Zhi-Hua Ran, Department of Gastroenterology, Renji Hospital, Shanghai Institute of Digestive Disease, Shanghai Jiao Tong University, School of Medicine, Shanghai 200001, China
Author contributions: Dong XW and Zheng Q completed searches, collected data and drafted the manuscript; Zhu MM and Tong JL conducted the meta-analysis, reviewed the data and the manuscript; Ran ZH supervised the whole study and edited the manuscript.
Correspondence to: Qing Zheng, Associate Professor, Department of Gastroenterology, Renji Hospital, Shanghai Institute of Digestive Disease, Shanghai Jiao Tong University, School of Medicine, Shanghai 200001, China. qingzheng101@yahoo.com
Telephone: +86-21-53882212 Fax: +86-21-63266027
Received: February 2, 2010
Revised: March 30, 2010
Accepted: April 6, 2010
Published online: July 7, 2010
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.

Keywords: Methyltransferases; Inflammatory bowel diseases; Meta-analysis; Adverse drug reactions; Bone marrow toxicity