ReviewJournal of gastroenterology2018
Pharmacogenetics of thiopurines for inflammatory bowel disease in East Asia: prospects for clinical application of NUDT15 genotyping.
Review in Journal of gastroenterology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers, 5 of them syntheses that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
44 citing papers in PubMed, 5 syntheses or guidelines pooled it, 80 citations in OpenAlex.
- Innovating Thiopurine Therapeutic Drug Monitoring: A Systematic Review and Meta-Analysis on DNA-Thioguanine Nucleotides (DNA-TG) as an Inclusive Biomarker in Thiopurine Therapy.Clinical pharmacokinetics · 2024Pooled it
- Association ofHaematologica · 2024Pooled it
- Factors predicting clinical and endoscopic remission with placebo therapy in East Asian patients with ulcerative colitis: a systematic review and meta-analysis.European journal of clinical pharmacology · 2022Pooled it
- The clinical efficacy of azathioprine as maintenance treatment for autoimmune pancreatitis: a systematic review and meta-analysis.Journal of gastroenterology · 2021Pooled it
- Association between the c.415C > T, c.52G > A, and 36_37insGGAGTC polymorphisms ofDrug design, development and therapy · 2019Pooled it
- Early proactive monitoring of DNA-thioguanine in patients with Crohn's disease predicts thiopurine-induced late leucopenia in NUDT15/TPMT normal metabolizers.World journal of gastroenterology · 2024Trial
- Withdrawal of thiopurines in Crohn's disease treated with scheduled adalimumab maintenance: a prospective randomised clinical trial (DIAMOND2).Journal of gastroenterology · 2019Trial
- Association of Variants in Candidate Pharmacogenes with Response to Mercaptopurine and Methotrexate in Pediatric Acute Lymphoblastic Leukemia: A Single-Center Experience from Croatia.Oncology and therapy · 2026Article
- HLA-DQB1*03:01 and HLA-DQA1*05:05 as key genetic determinants of infliximab response and immunogenicity in Japanese patients with inflammatory bowel disease.Journal of gastroenterology · 2026Article
- Increasing age at diagnosis raises malignancy risk and aminosalicylate intolerance influences therapeutic strategies in ulcerative colitis: a multicenter I‑BRITE cohort study.Journal of gastroenterology · 2025Article
- Asian-Pacific perspectives on the management of very early-onset inflammatory bowel disease.Intestinal research · 2025Review
- Assessing the Occurrence and Influence of Cancer Chemotherapy-Related Pharmacogenetic Alleles in the Chilean Population.Pharmaceutics · 2024Article
- Identification of hub programmed cell death-related genes and immune infiltration in Crohn's disease using bioinformatics.Frontiers in genetics · 2024Article
- Comparative assessment of anti-cancer drugs against NUDT15 variants to prevent leucopenia side effect in leukemia patients.Journal, genetic engineering & biotechnology · 2023Article
- Pharmacogenomics of Old and New Immunosuppressive Drugs for Precision Medicine in Kidney Transplantation.Journal of clinical medicine · 2023Review
- Treatment escalation and de-escalation decisions in Crohn's disease: Delphi consensus recommendations from Japan, 2021.Journal of gastroenterology · 2023Review
- Population-Specific Distribution ofTherapeutics and clinical risk management · 2023Article
- IBD barriers across the continents - East Asia.Therapeutic advances in gastroenterology · 2023Review
- Personalized medicine to implementation science: Thiopurines set for the leap.JGH open : an open access journal of gastroenterology and hepatology · 2022Article
- Validity of Diagnostic Algorithms for Inflammatory Bowel Disease in Japanese Hospital Claims Data.International journal of environmental research and public health · 2022Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The thiopurine drugs 6-mercaptopurine (6-MP) and azathiopurine (AZA) are widely used to treat inflammatory bowel disease. However, the incidence of adverse reactions is high, particularly in Asia, and the mechanisms of toxicity in Asian populations remain unclear. Thiopurine S-methyltransferase (TPMT) is a well-known enzyme that inactivates AZA or 6-MP through methylation and is one of the few pharmacogenetic predictors used in clinical settings in Western countries. Individuals carrying TPMT-deficient genetic variants require reduced drug doses, but this treatment modification is are not applicable to East Asian populations. Several genes code thiopurine-metabolizing enzymes, including TPMT, multidrug-resistance protein 4, and inosine triphosphatase. These genes have been studied as candidate pharmacogenetic markers; however, it remains unclear why Asian populations seem to be more intolerant than other ethnic groups to a full dose of thiopurines. A genome-wide association approach to identify Asian-specific pharmacogenetic markers in Korean patients with Crohn's disease revealed that a non-synonymous single nucelotide polymorphism in nucleoside diphosphate-linked moiety X-type motif 15 (NUDT15) which causes p.Arg139Cys was strongly associated with thiopurine-induced early leukopenia. Six common haplotypes of NUDT15 were reported, and five variants showed medium-to-low enzyme activities, compared with the wild haplotype. NUDT15 hydrolyzes the thiopurine active metabolites 6-thio-GTP and 6-thio-dGTP; variants of NUDT15 had lower enzyme activities, causing higher levels of thiopurine active metabolites, resulting in thiopurine-induced leukopenia. In clinical application, NUDT15 genotyping is a good candidate for predicting thiopurine toxicity in East Asian populations. However, the association of NUDT15 diplotypes with thiopurine toxicity remains unclear. Further analyses with large cohorts to confirm the clinical effects of each haplotype are planned.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.