TPMT

Last update 08 May 2025

Basic Info

Synonyms

Thiopurine methyltransferase, thiopurine S-methyltransferase, TPMT

Introduction

Catalyzes the S-methylation of thiopurine drugs such as 6-mercaptopurine (also called mercaptopurine, 6-MP or its brand name Purinethol) and 6-thioguanine (also called tioguanine or 6-TG) using S-adenosyl-L-methionine as the methyl donor (PubMed:18484748, PubMed:657528). TPMT activity modulates the cytotoxic effects of thiopurine prodrugs. A natural substrate for this enzyme has yet to be identified.

100 Clinical Results associated with TPMT

100 Translational Medicine associated with TPMT

0 Patents (Medical) associated with TPMT

1,541

Literatures (Medical) associated with TPMT

01 Jul 2025·Critical Reviews in Oncology/Hematology

Pharmacogenomics in pediatric oncology patients with solid tumors related to chemotherapy-induced toxicity: A systematic review

Review

Author: Uvdal, Hanna ; Hansson, Paula ; Blacker, Christopher ; Wadelius, Mia ; Green, Henrik ; Ljungman, Gustaf

Chemotherapy-induced toxicities remain challenging in pediatric oncology, affecting patient outcomes, hospital stays, and quality of life. Genetic variation can partly explain these toxicities, and pharmacogenomics could potentially optimize treatment. This review provides an overview of pharmacogenomic studies in relation to chemotherapy-induced toxicity in children with solid tumors. A systematic literature search was performed in PubMed, Embase, and Web of Science following PRISMA guidelines. Two independent reviewers assessed eligibility, risk of bias using ROBINS-I, and extracted data. Out of 9000 articles screened, 279 were deemed relevant, and 59 met the inclusion criteria by focusing on children with solid tumors and pharmacogenomics in relation to chemotherapy-induced toxicity. Following risk of bias assessment, 24 articles with low to moderate risk of bias were summarized. Identifying specific SNPs associated with toxicities proved challenging due to variability across studies. For methotrexate, the genes ABCC2, MTHFR, and SXR were associated with myelosuppression and hepatotoxicity. The genes ABCC3, COMT, ERCC2, GSTP1, GSTT1, LRP2, SLC22A2, and TPMT showed associations with ototoxicity due to platinum-based drugs. Anthracycline-induced cardiotoxicity was associated with CBR2, CELF4, GSTM1, HAS3, RARG, and SLC28A3, and further with HNMT and SLC22A2 in younger children, with ABCB4 in females, and with SULT2B1 in males. A dose-dependent effect of CELF4 on cardiotoxicity was noted with anthracycline doses over 300 mg/m². This review highlights the complexity and variability of pharmacogenomic associations with chemotherapy-induced toxicities in pediatric oncology. While certain genetic variants show associations with specific toxicities, larger multinational/center studies are needed to strengthen the associations and improve clinical guidelines.

01 Jun 2025·Gene

Pharmacogenomic variants in the Pumi population from Yunnan, China

Article

Author: Zhang, Xinyu ; Wang, Ying ; Zhang, Chan ; Cheng, Yujing ; Yang, Xin ; Li, Qi ; Chen, Wanlu

BACKGROUNDPharmacogenomics is used to identify genetic factors that influence drug responses, thereby optimizing therapeutic outcomes and reducing adverse effects. The objective of this study is to identify pharmacogenomic variations and their clinical relevance to drug metabolism and toxicity within the Pumi population.METHODSEighty-two genetic variants in 43 genes were genotyped in 200 unrelated Pumi individuals using the Agena MassARRAY Assay. Chi-square tests, adjusted for multiple comparisons with Bonferroni correction, were used to compare genotype frequency divergences between the Pumi population and 26 other populations. Population genetic structure diversity and pairwise F-statistics (Fst) were assessed across 27 populations using Structure v2.3.1 and Arlequin v3.5 software.RESULTSAfter Bonferroni correction, a number of single nucleotide variations (SNVs) exhibited significant differences in frequency between the Pumi population and other populations. The allele frequencies of ADH1A rs975833, ADH1B rs1229984, TPMT rs1142345, and CYP2A6 rs8192726 in the Pumi population were notably different from the East Asian population or the other 26 populations. PharmGKB data indicate that rs1229984, rs1142345, and rs8192726 are associated with the metabolic efficiency of acetaldehyde, mercaptopurine, and efavirenz, respectively. Additionally, the genetic structure analysis (K = 5) and pairwise Fst calculations revealed that the Pumi population shared a similar genetic background with CHB (Fst = 0.031), JPT (Fst = 0.033), KHV (Fst = 0.035), CHS (Fst = 0.036), and CDX (Fst = 0.037) populations.CONCLUSIONOur findings reveal unique genetic variations and biomarkers within the Pumi population, which contributes pharmacogenomic insights and theoretical foundations for personalized medicine tailored to the Pumi population.

01 Apr 2025·Journal of Advanced Research

Association of intestinal anti-inflammatory drug target genes with psychiatric Disorders: A Mendelian randomization study

Article

Author: Zhao, Guorui ; Kang, Zhewei ; Liao, Yundan ; Sun, Junyuan ; Sun, Yaoyao ; Feng, Xiaoyang ; Yue, Weihua ; Zhang, Yuyanan ; Lu, Zhe

INTRODUCTIONPsychiatric disorders present a substantial global public health burden with limited drug options. The gut-brain axis connects inflammatory bowel diseases and psychiatric disorders, which often have comorbidities. While some evidence hints at anti-inflammatory drugs aiding in treating psychiatric conditions, the specific effects of intestinal anti-inflammatory drugs remain unclear.OBJECTIVESThis study investigates the causal effect of intestinal anti-inflammatory drug targets on psychiatric disorders. We hypothesize that these drug targets may offer new insights into the treatment and prevention of such disorders. Additionally, we explore gut microbiota's mediating role between drug target genes and psychiatric disorders.METHODSWe performed two-sample Mendelian randomization (MR) using summary data from existing expression quantitative trait loci (eQTL) and protein QTL in the brain, along with public genome-wide association studies of disease. We also explored gut microbiota's mediating effect. The statistics encompassed six psychiatric disorders involving 9,725-500,199 individuals. Colocalization analysis enhanced the MR evidence.RESULTSWe uncovered a causal link between TPMT (a target of olsalazine) expression in the amygdala and bipolar disorder (BD) risk (odds ratio [OR] = 1.08; P = 4.29 × 10^-4). This association was observed even when the sigmoid colon and whole blood eQTL were considered as exposures. Colocalization analysis revealed a shared genetic variant (rs11751561) between TPMT expression and BD, with a posterior probability of 61.6 %. Interestingly, this causal effect was influenced by a decrease in the gut microbiota abundance of the genus Roseburia (effect proportion = 10.05 %). Moreover, elevated ACAT1 expression was associated with higher obsessive-compulsive disorder risk (OR = 1.62; P = 3.64 × 10^-4; posterior probability = 3.1 %).CONCLUSIONThese findings provide novel targets for the treatment of psychiatric disorders, underscore the potential of repurposing olsalazine, and emphasize the importance of TPMT and ACAT1 in future drug development.

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