Association between thiopurine S-methyltransferase polymorphisms and thiopurine-induced adverse drug reactions in patients with inflammatory bowel disease: a meta-analysis.
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 r...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2015-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC4370632?pdf=render |
| _version_ | 1818943725078839296 |
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| author | Yue-Ping Liu Hai-Yan Wu Xiang Yang Han-Qing Xu Yong-Chuan Li Da-Chuan Shi Jun-Fu Huang Qing Huang Wei-Ling Fu |
| author_facet | Yue-Ping Liu Hai-Yan Wu Xiang Yang Han-Qing Xu Yong-Chuan Li Da-Chuan Shi Jun-Fu Huang Qing Huang Wei-Ling Fu |
| author_sort | Yue-Ping Liu |
| collection | DOAJ |
| description | 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.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.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.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. |
| first_indexed | 2024-12-20T07:31:53Z |
| format | Article |
| id | doaj.art-1912f0afa5294176ad1523b3189781f3 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-20T07:31:53Z |
| publishDate | 2015-01-01 |
| publisher | Public Library of Science (PLoS) |
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| series | PLoS ONE |
| spelling | doaj.art-1912f0afa5294176ad1523b3189781f32022-12-21T19:48:24ZengPublic Library of Science (PLoS)PLoS ONE1932-62032015-01-01103e012174510.1371/journal.pone.0121745Association between thiopurine S-methyltransferase polymorphisms and thiopurine-induced adverse drug reactions in patients with inflammatory bowel disease: a meta-analysis.Yue-Ping LiuHai-Yan WuXiang YangHan-Qing XuYong-Chuan LiDa-Chuan ShiJun-Fu HuangQing HuangWei-Ling FuThiopurine 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.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.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.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.http://europepmc.org/articles/PMC4370632?pdf=render |
| spellingShingle | Yue-Ping Liu Hai-Yan Wu Xiang Yang Han-Qing Xu Yong-Chuan Li Da-Chuan Shi Jun-Fu Huang Qing Huang Wei-Ling Fu Association between thiopurine S-methyltransferase polymorphisms and thiopurine-induced adverse drug reactions in patients with inflammatory bowel disease: a meta-analysis. PLoS ONE |
| title | Association between thiopurine S-methyltransferase polymorphisms and thiopurine-induced adverse drug reactions in patients with inflammatory bowel disease: a meta-analysis. |
| title_full | Association between thiopurine S-methyltransferase polymorphisms and thiopurine-induced adverse drug reactions in patients with inflammatory bowel disease: a meta-analysis. |
| title_fullStr | Association between thiopurine S-methyltransferase polymorphisms and thiopurine-induced adverse drug reactions in patients with inflammatory bowel disease: a meta-analysis. |
| title_full_unstemmed | Association between thiopurine S-methyltransferase polymorphisms and thiopurine-induced adverse drug reactions in patients with inflammatory bowel disease: a meta-analysis. |
| title_short | Association between thiopurine S-methyltransferase polymorphisms and thiopurine-induced adverse drug reactions in patients with inflammatory bowel disease: a meta-analysis. |
| title_sort | association between thiopurine s methyltransferase polymorphisms and thiopurine induced adverse drug reactions in patients with inflammatory bowel disease a meta analysis |
| url | http://europepmc.org/articles/PMC4370632?pdf=render |
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