title: Association between thiopurine S-methyltransferase polymorphisms and thiopurine-induced adverse drug reactions in patients with inflammatory bowel disease: a meta-analysis.
abstract: OBJECTIVE
  Thiopurine drugs are well established treatments in the management of inflammatory bowel disease (IBD), but their use is limited by significant adverse drug reactions (ADRs). Thiopurine S-methyltransferase (TPMT) is an important enzyme involved in thiopurine metabolism. Several clinical guidelines recommend determining TPMT genotype or phenotype before initiating thiopurine therapy. Although several studies have investigated the association between TPMT polymorphisms and thiopurine-induced ADRs, the results are inconsistent. The purpose of this study is to evaluate whether there is an association between TPMT polymorphisms and thiopurine-induced ADRs using meta-analysis.
  
  
  METHODS
  We explored PubMed, Web of Science and Embase for articles on TPMT polymorphisms and thiopurine-induced ADRs. Studies that compared TPMT polymorphisms with-ADRs and without-ADRs in IBD patients were included. Relevant outcome data from all the included articles were extracted and the pooled odds ratio (OR) with corresponding 95% confidence intervals were calculated using Revman 5.3 software.
  
  
  RESULTS
  Fourteen published studies, with a total of 2,206 IBD patients, which investigated associations between TPMT polymorphisms and thiopurine-induced ADRs were included this meta-analysis. Our meta-analysis demonstrated that TPMT polymorphisms were significantly associated with thiopurine-induced overall ADRs and bone marrow toxicity; pooled ORs were 3.36 (95%CI: 1.82-6.19) and 6.67 (95%CI: 3.88-11.47), respectively. TPMT polymorphisms were not associated with the development of other ADRs including hepatotoxicity, pancreatitis, gastric intolerance, flu-like symptoms and skin reactions; the corresponding pooled ORs were 1.27 (95%CI: 0.60-2.71), 0.97 (95%CI: 0.38-2.48), 1.82 (95%CI: 0.93-3.53), 1.28 (95%CI: 0.47-3.46) and 2.32 (95%CI: 0.86-6.25), respectively.
  
  
  CONCLUSIONS
  Our meta-analysis demonstrated an association of TPMT polymorphisms with overall thiopurine-induced ADRs and bone marrow toxicity, but not with hepatotoxicity, pancreatitis, flu-like symptoms, gastric intolerance and skin reactions. These findings suggest that pretesting the TPMT genotype could be helpful in clinical practice before initiating thiopurine therapy. However, white blood cell count analysis should be the mainstay for follow-up.
authors: Department of Laboratory Medicine, Southwest Hospital, Third Military Medical University, Chongqing, 400038, China.
authors: Yue-Ping
authors: YP
authors: Liu
authors: Department of Laboratory Medicine, Southwest Hospital, Third Military Medical University, Chongqing, 400038, China.
authors: Hai-Yan
authors: HY
authors: Wu
authors: Department of Laboratory Medicine, Southwest Hospital, Third Military Medical University, Chongqing, 400038, China.
authors: Xiang
authors: X
authors: Yang
authors: Department of Laboratory Medicine, Southwest Hospital, Third Military Medical University, Chongqing, 400038, China.
authors: Han-Qing
authors: HQ
authors: Xu
authors: Department of Laboratory Medicine, Southwest Hospital, Third Military Medical University, Chongqing, 400038, China.
authors: Yong-Chuan
authors: YC
authors: Li
authors: Department of Laboratory Medicine, Southwest Hospital, Third Military Medical University, Chongqing, 400038, China.
authors: Da-Chuan
authors: DC
authors: Shi
authors: Department of Laboratory Medicine, Southwest Hospital, Third Military Medical University, Chongqing, 400038, China.
authors: Jun-Fu
authors: JF
authors: Huang
authors: Department of Laboratory Medicine, Southwest Hospital, Third Military Medical University, Chongqing, 400038, China.
authors: Qing
authors: Q
authors: Huang
authors: Department of Laboratory Medicine, Southwest Hospital, Third Military Medical University, Chongqing, 400038, China.
authors: Wei-Ling
authors: WL
authors: Fu
mesh_terms: D064420:Drug-Related Side Effects and Adverse Reactions / Q000201:enzymology* / Q000235:genetics*; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000188:drug therapy*; D008780:Methyltransferases / Q000235:genetics*; D011110:Polymorphism, Genetic; D011687:Purines / Q000009:adverse effects* / Q000627:therapeutic use
chemical_list: D011687:Purines; D008780:Methyltransferases; C022745:thiopurine methyltransferase