BIOMAT Database Logo BIOMAT Database Logo

Association between thiopurine S-methyltransferase polymorphisms and thiopurine-induced adverse drug reactions in patients with inflammatory bowel disease: a meta-analysis. 2015

Yue-Ping Liu, and Hai-Yan Wu, and Xiang Yang, and Han-Qing Xu, and Yong-Chuan Li, and Da-Chuan Shi, and Jun-Fu Huang, and Qing Huang, and Wei-Ling Fu
Department of Laboratory Medicine, Southwest Hospital, Third Military Medical University, Chongqing, 400038, China.

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.

UI MeSH Term Description Entries
D008780 Methyltransferases A subclass of enzymes of the transferase class that catalyze the transfer of a methyl group from one compound to another. (Dorland, 28th ed) EC 2.1.1. Methyltransferase
D011110 Polymorphism, Genetic The regular and simultaneous occurrence in a single interbreeding population of two or more discontinuous genotypes. The concept includes differences in genotypes ranging in size from a single nucleotide site (POLYMORPHISM, SINGLE NUCLEOTIDE) to large nucleotide sequences visible at a chromosomal level. Gene Polymorphism,Genetic Polymorphism,Polymorphism (Genetics),Genetic Polymorphisms,Gene Polymorphisms,Polymorphism, Gene,Polymorphisms (Genetics),Polymorphisms, Gene,Polymorphisms, Genetic
D011687 Purines A series of heterocyclic compounds that are variously substituted in nature and are known also as purine bases. They include ADENINE and GUANINE, constituents of nucleic acids, as well as many alkaloids such as CAFFEINE and THEOPHYLLINE. Uric acid is the metabolic end product of purine metabolism.
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D015212 Inflammatory Bowel Diseases Chronic, non-specific inflammation of the GASTROINTESTINAL TRACT. Etiology may be genetic or environmental. This term includes CROHN DISEASE and ULCERATIVE COLITIS. Bowel Diseases, Inflammatory,Inflammatory Bowel Disease
D064420 Drug-Related Side Effects and Adverse Reactions Disorders that result from the intended use of PHARMACEUTICAL PREPARATIONS. Included in this heading are a broad variety of chemically-induced adverse conditions due to toxicity, DRUG INTERACTIONS, and metabolic effects of pharmaceuticals. Drug-Related Side Effects and Adverse Reaction,Adverse Drug Event,Adverse Drug Reaction,Drug Side Effects,Drug Toxicity,Side Effects of Drugs,Toxicity, Drug,Adverse Drug Events,Adverse Drug Reactions,Drug Event, Adverse,Drug Events, Adverse,Drug Reaction, Adverse,Drug Reactions, Adverse,Drug Related Side Effects and Adverse Reaction,Drug Related Side Effects and Adverse Reactions,Drug Side Effect,Drug Toxicities,Effects, Drug Side,Reactions, Adverse Drug,Side Effect, Drug,Side Effects, Drug,Toxicities, Drug

Related Publications

Yue-Ping Liu, and Hai-Yan Wu, and Xiang Yang, and Han-Qing Xu, and Yong-Chuan Li, and Da-Chuan Shi, and Jun-Fu Huang, and Qing Huang, and Wei-Ling Fu
Association between Thiopurine S-Methyltransferase Polymorphisms and Azathioprine-Induced Adverse Drug Reactions in Patients with Autoimmune Diseases: A Meta-Analysis.
January 2015, PloS one,
Yue-Ping Liu, and Hai-Yan Wu, and Xiang Yang, and Han-Qing Xu, and Yong-Chuan Li, and Da-Chuan Shi, and Jun-Fu Huang, and Qing Huang, and Wei-Ling Fu
Thiopurine S-methyltransferase (TPMT) genotype does not predict adverse drug reactions to thiopurine drugs in patients with inflammatory bowel disease.
August 2003, Alimentary pharmacology & therapeutics,
Yue-Ping Liu, and Hai-Yan Wu, and Xiang Yang, and Han-Qing Xu, and Yong-Chuan Li, and Da-Chuan Shi, and Jun-Fu Huang, and Qing Huang, and Wei-Ling Fu
Azathioprine therapy and adverse drug reactions in patients with inflammatory bowel disease: impact of thiopurine S-methyltransferase polymorphism.
August 2002, Pharmacogenetics,
Yue-Ping Liu, and Hai-Yan Wu, and Xiang Yang, and Han-Qing Xu, and Yong-Chuan Li, and Da-Chuan Shi, and Jun-Fu Huang, and Qing Huang, and Wei-Ling Fu
Correlation between Thiopurine S-Methyltransferase Genotype and Adverse Events in Inflammatory Bowel Disease Patients.
August 2019, Medicina (Kaunas, Lithuania),
Yue-Ping Liu, and Hai-Yan Wu, and Xiang Yang, and Han-Qing Xu, and Yong-Chuan Li, and Da-Chuan Shi, and Jun-Fu Huang, and Qing Huang, and Wei-Ling Fu
Thiopurine S-methyltransferase polymorphisms and thiopurine toxicity in treatment of inflammatory bowel disease.
July 2010, World journal of gastroenterology,
Yue-Ping Liu, and Hai-Yan Wu, and Xiang Yang, and Han-Qing Xu, and Yong-Chuan Li, and Da-Chuan Shi, and Jun-Fu Huang, and Qing Huang, and Wei-Ling Fu
Thiopurine methyltransferase gene polymorphisms in Chinese patients with inflammatory bowel disease.
January 2009, Digestion,
Yue-Ping Liu, and Hai-Yan Wu, and Xiang Yang, and Han-Qing Xu, and Yong-Chuan Li, and Da-Chuan Shi, and Jun-Fu Huang, and Qing Huang, and Wei-Ling Fu
Analysis of thiopurine S-methyltransferase genotypes in Japanese patients with inflammatory bowel disease.
January 2008, Internal medicine (Tokyo, Japan),
Yue-Ping Liu, and Hai-Yan Wu, and Xiang Yang, and Han-Qing Xu, and Yong-Chuan Li, and Da-Chuan Shi, and Jun-Fu Huang, and Qing Huang, and Wei-Ling Fu
Adverse reactions to azathioprine cannot be predicted by thiopurine S-methyltransferase genotype in Japanese patients with inflammatory bowel disease.
July 2009, Journal of gastroenterology and hepatology,
Yue-Ping Liu, and Hai-Yan Wu, and Xiang Yang, and Han-Qing Xu, and Yong-Chuan Li, and Da-Chuan Shi, and Jun-Fu Huang, and Qing Huang, and Wei-Ling Fu
The impact of thiopurine-S-methyltransferase genotype on the adverse drug reactions to azathioprine in patients with inflammatory bowel diseases.
January 2013, Bratislavske lekarske listy,
Yue-Ping Liu, and Hai-Yan Wu, and Xiang Yang, and Han-Qing Xu, and Yong-Chuan Li, and Da-Chuan Shi, and Jun-Fu Huang, and Qing Huang, and Wei-Ling Fu
Thiopurine S-Methyltransferase gene polymorphisms in a healthy Slovak population and pediatric patients with inflammatory bowel disease.
January 2013, Nucleosides, nucleotides & nucleic acids,
Copied contents to your clipboard!