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Thiopurine S-methyltransferase

TPMT, thiopurine methyltransferase, thiopurine S-methyltransferase
This gene encodes the enzyme that metabolizes thiopurine drugs via S-adenosyl-L-methionine as the S-methyl donor and S-adenosyl-L-homocysteine as a byproduct. Thiopurine drugs such as 6-mercaptopurine are used as chemotherapeutic agents. Genetic polymorphisms that affect this enzymatic activity are correlated with variations in sensitivity and toxicity to such drugs within individuals. A pseudogene for this locus is located on chromosome 18q. [provided by RefSeq, Jul 2008] (from NCBI)
Top mentioned proteins: HAD, CAN, IBD, POLYMERASE, AGE
Papers on TPMT
NUDT15 variant is the most common variant associated with thiopurine-induced early leukopenia and alopecia in Korean pediatric patients with Crohn's disease.
New
Kim et al., Ulsan, South Korea. In Eur J Gastroenterol Hepatol, Feb 2016
In addition to the mutations of TPMT gene, the NUDT15 c.415C>T variant was recently identified to have a strong association with thiopurine-induced early leukopenia.
Whole genome and normalized mRNA sequencing reveal genetic status of TK6, WTK1, and NH32 human B-lymphoblastoid cell lines.
New
Dobrovolsky et al., United States. In Mutat Res Genet Toxicol Environ Mutagen, Feb 2016
SNPs in the thiopurine S-methyltransferase (TPMT) gene (TPMT*3A SNP), and in the xenobiotic metabolizing enzyme, NADPH quinine oxidoreductase 1 (NQO1) gene (NQO1*2 SNP), are both associated with decreased enzyme activity.
TPMT and ITPA genetic variants in Lithuanian inflammatory bowel disease patients: Prevalence and azathioprine-related side effects.
New
Kupcinskas et al., Kaunas, Lithuania. In Adv Med Sci, Jan 2016
Genetic polymorphisms in thiopurine methyltransferase (TPMT) and inosine triphosphate pyrophosphatase (ITPA) were linked with toxicity of azathioprine (AZA).
Personalized medicine in sarcoidosis: predict responders and nonresponders.
Review
New
Petrek, Olomouc, Czech Republic. In Curr Opin Pulm Med, Sep 2015
RECENT FINDINGS: No firm evidence is available for introducing genotyping metabolizing enzymes and/or transporters (Cytochrome P450, TPMT, ABCB1 and so on) despite drugs they target (azathioprine and methotrexate) are used in sarcoidosis.
TPMT Polymorphism: When Shield Becomes Weakness.
Review
New
Kuntal et al., Allahābād, India. In Interdiscip Sci, Sep 2015
UNASSIGNED: Thiopurine methyltransferase (TPMT) is a cytoplasmic transmethylase present in both prokaryotes and eukaryotes.
Use of Thiopurines in Inflammatory Bowel Disease: A Consensus Statement by the Korean Association for the Study of Intestinal Diseases (KASID).
Review
New
IBD Study Group of the Korean Association for the Study of Intestinal Diseases et al., Suwŏn, South Korea. In Intestinal Res, Jul 2015
RESULTS: The consensus statements comprised four parts: (1) pre-treatment evaluation and management strategy, including value of thiopurine S-methyltransferase screening, dosing schedule, and novel biomarkers for predicting thiopurine-induced leukopenia; (2) treatment with thiopurines with regards to optimal duration of thiopurine treatment and long-term outcomes of combination therapy with anti-tumor necrosis factors; (3) safety of thiopurines, especially during pregnancy and lactation; and (4) monitoring side effects or efficacy of therapy using biomarkers.
Update on thiopurine pharmacogenetics in inflammatory bowel disease.
Review
New
Barclay et al., Dunedin, New Zealand. In Pharmacogenomics, Jul 2015
While thiopurine S-methyltransferase deficiency was the first pharmacogenetic phenomenon to be recognized to influence thiopurine toxicity and reliably predict leukopenia, it does not predict other adverse effects, nor does it explain most cases of thiopurine resistance.
[Optimized thiopurine treatment in chronic inflammatory bowel disease].
New
Nielsen et al., In Ugeskr Laeger, Jul 2015
An increasing body of evidence suggests that a large part of the observed non-pancreatic side effects and poor responses can be solved by tailoring thiopurine therapy using measurement of thiopurine methyltransferase and metabolites and by using a combination therapy with low-dose thiopurines and allopurinol.
Association between Thiopurine S-Methyltransferase Polymorphisms and Azathioprine-Induced Adverse Drug Reactions in Patients with Autoimmune Diseases: A Meta-Analysis.
Huang et al., Chongqing, China. In Plos One, 2014
Thiopurine S-methyltransferase (TPMT) is an important enzyme involved in AZA metabolism.
Getting the best out of thiopurine therapy: thiopurine S-methyltransferase and beyond.
Review
Sanderson et al., London, United Kingdom. In Biomark Med, 2014
Thiopurine S-methyltransferase and thiopurine metabolite levels have emerged as companion diagnostics with crucial roles in facilitating safe and effective treatment.
A common missense variant in NUDT15 confers susceptibility to thiopurine-induced leukopenia.
Impact
Song et al., Seoul, South Korea. In Nat Genet, 2014
This leukopenia is associated with genetic variation in TPMT (encoding thiopurine S-methyltransferase). Despite a lower frequency of TPMT mutations in Asians, the incidence of thiopurine-induced leukopenia is higher in Asians than in individuals of European descent.
Inter and intra-ethnic differences in the distribution of the molecular variants of TPMT, UGT1A1 and MDR1 genes in the South Indian population.
GeneRIF
Adithan et al., Pondicherry, India. In Mol Biol Rep, 2012
The distribution of TPMT, UGT1A1 and MDR1 gene polymorphisms of the South Indian population was significantly different from other populations.
High TPMT enzyme activity does not explain drug resistance due to preferential 6-methylmercaptopurine production in patients on thiopurine treatment.
GeneRIF
Barclay et al., Christchurch, New Zealand. In Aliment Pharmacol Ther, 2012
High TPMT enzyme activity does not explain drug resistance Many of these patients preferentially produce the toxic 6-methylmercaptopurine metabolites (6-MMP) rather than the active 6-thioguanine nucleotides (6-TGN)
Thiopurine S-methyltransferase phenotype-genotype correlation in children with acute lymphoblastic leukemia.
GeneRIF
Droździk et al., Poznań, Poland. In Acta Pol Pharm, 2012
TPMT activity was measured in RBC by HPLC method.
High prevalence of polymorphism and low activity of thiopurine methyltransferase in patients with inflammatory bowel disease.
GeneRIF
Luzza et al., Catanzaro, Italy. In Eur J Intern Med, 2012
Inflammatory bowel disease patients may have significantly higher prevalence of TPMT polymorphism and, even more, low activity.
Prevalence of mutations in thiopurine S-methyltransferase gene among Slovak IBD patients.
GeneRIF
Batovsky et al., Bratislava, Slovakia. In Bratisl Lek Listy, 2011
aim of this study was to determine the frequency of the four most common allelic variants of TPMT gene in the population of Slovak IBD patients.TPMT genetic polymorphisms lead to dose-related hematopoetic toxicity
Genetic variants in TPMT and COMT are associated with hearing loss in children receiving cisplatin chemotherapy.
Impact
GeneRIF
CPNDS Consortium et al., Vancouver, Canada. In Nat Genet, 2009
the strong associations of cisplatin-induced hearing loss with specific genetic variants in TPMT were identified
Pharmacogenetics, drug-metabolizing enzymes, and clinical practice.
Review
Impact
Begg et al., Christchurch, New Zealand. In Pharmacol Rev, 2006
Drugs (and enzymes) for which there is a reasonable evidence base supporting genotyping or phenotyping include suxamethonium/mivacurium (butyrylcholinesterase), and azathioprine/6-mercaptopurine (thiopurine methyltransferase).
Azathioprine dosed by thiopurine methyltransferase activity for moderate-to-severe atopic eczema: a double-blind, randomised controlled trial.
Impact
Reynolds et al., Newcastle upon Tyne, United Kingdom. In Lancet, 2006
We aimed to assess the safety and efficacy of azathioprine as systemic monotherapy for moderate-to-severe atopic eczema, and the therapeutic importance of the thiopurine methyltransferase (TPMT) polymorphism (a key determinant of azathioprine-induced myelotoxicity) by using TPMT enzyme activity to establish azathioprine dose.
Pharmacogenomic discovery approaches: will the real genes please stand up?
Review
Impact
McLeod et al., Saint Louis, United States. In J Clin Oncol, 2005
Candidate gene approaches have led to clinical tests for toxicity avoidance (eg, TPMT, UGT1A1) and efficacy prediction (eg, epidermal growth factor receptor-activating mutations).
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