ArticleJournal of gastroenterology2018
NUDT15 codon 139 is the best pharmacogenetic marker for predicting thiopurine-induced severe adverse events in Japanese patients with inflammatory bowel disease: a multicenter study.
Article 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 70 papers, 3 of them syntheses that pooled it.
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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.
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Who cites it
70 citing papers in PubMed, 3 syntheses or guidelines pooled it, 123 citations in OpenAlex.
- Blood-test monitoring strategies for patients established on immune-suppressing drugs: a mixed-methods study.Health technology assessment (Winchester, England) · 2026Pooled it
- Pooled it
- The clinical efficacy of azathioprine as maintenance treatment for autoimmune pancreatitis: a systematic review and meta-analysis.Journal of gastroenterology · 2021Pooled it
- Withdrawal of thiopurines in Crohn's disease treated with scheduled adalimumab maintenance: a prospective randomised clinical trial (DIAMOND2).Journal of gastroenterology · 2019Trial
- Comprehensive overview of the global pharmacogenetic and functional variability in NUDT15.Human genomics · 2026Review
- Tacrolimus therapy for ulcerative colitis: a retrospective study of factors associated with inducing and maintaining remission.BMC gastroenterology · 2026Article
- The role of pharmacogenetics in the therapy regimen of acute lymphoblastic leukemia in children: recent discoveries and future perspectives.Pharmacological reports : PR · 2026Review
- Real-world use of biologics during the first year of treatment for newly diagnosed Crohn's disease in Japan: a claims analysis from 2010 to 2021.Intestinal research · 2026Article
- RAB19, SERPINB9P1, and Pancreatitis in Patients Taking Azathioprine in Routine Clinical Practice: Genome and Transcriptome-Wide Association Studies.Clinical pharmacology and therapeutics · 2025Article
- 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
- Autoimmune Hepatitis and Drug-Induced Liver Injury in Japan.Journal of clinical medicine · 2025Review
- Optimization of Preemptive Therapy for Cytomegalovirus Infections With Valganciclovir Based on Therapeutic Drug Monitoring: Protocol for a Phase II, Single-Center, Single-Arm Trial.JMIR research protocols · 2025Article
- Bone Marrow Aplasia and Neutropenic Fever Following Azathioprine Dose Escalation in a TPMT-Deficient Patient with Crohn's Disease and Psoriatic Arthritis-A CARE-Compliant Case.Clinics and practice · 2025Article
- Induction Therapy With Oral Tacrolimus Provides Long-Term Benefit in Thiopurine-Naïve Refractory Ulcerative Colitis Patients Despite Low Serum Albumin Levels.JGH open : an open access journal of gastroenterology and hepatology · 2025Article
- Therapeutic Agents and Patient Characteristics Affecting Metabolism of Thiopurines in Patients with Inflammatory Bowel Disease.Fukushima journal of medical science · 2025Article
- Genetic association analysis and frequency of NUDT15*3 with thiopurine-induced myelosuppression in patients with inflammatory bowel disease in a large Dutch cohort.The pharmacogenomics journal · 2024Article
- Factors influencing the discontinuation of biologic therapies in patients with ulcerative colitis.Journal of pharmaceutical health care and sciences · 2024Article
- Nudt15-mediated inflammatory signaling contributes to divergent outcomes in leukemogenesis and hematopoiesis.Leukemia · 2024Article
- Real-world NUDT15 genotyping and thiopurine treatment optimization in inflammatory bowel disease: a multicenter study.Journal of gastroenterology · 2024Article
- Thiopurines exert harmful effects on spermatogenesis in Nudt15Journal of gastroenterology · 2024Article
10 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
40 authors at 14 institutions in 1 country.
Funding
Abstract
backgroundDespite NUDT15 variants showing significant association with thiopurine-induced adverse events (AEs) in Asians, it remains unclear which variants of NUDT15 or whether additional genetic variants should be tested to predict AEs. To clarify the best pharmacogenetic test to be used clinically, we performed association studies of NUDT15 variants and haplotypes with AEs, genome-wide association study (GWAS) to discover additional variants, and ROC analysis to select the model to predict severe AEs.
methodsOverall, 2630 patients with inflammatory bowel disease (IBD) were enrolled and genotyped for NUDT15 codon 139; 1291 patients were treated with thiopurines. diplotypes were analyzed in 970 patients, and GWASs of AEs were performed with 1221 patients using population-optimized genotyping array and imputation.
resultsWe confirmed the association of NUDT15 p.Arg139Cys with leukopenia and alopecia (p = 2.20E-63, 1.32E-69, OR = 6.59, 12.1, respectively), and found a novel association with digestive symptoms (p = 6.39E-04, OR = 1.89). Time to leukopenia was significantly shorter, and when leukopenia was diagnosed, thiopurine doses were significantly lower in Arg/Cys and Cys/Cys than in Arg/Arg. In GWASs, no additional variants were found to be associated with thiopurine-induced AEs. Despite strong correlation of leukopenia frequency with estimated enzyme activities based on the diplotypes (r
conclusionsGenotyping of NUDT15 codon 139 was sufficient to predict acute severe leukopenia and alopecia in Japanese patients with IBD.
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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.