ArticlePharmacogenomics2018
Predictive role of NUDT15 variants on thiopurine-induced myelotoxicity in Asian inflammatory bowel disease patients.
Article in Pharmacogenomics, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers, 2 of them syntheses that pooled it.
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Who cites it
22 citing papers in PubMed, 2 syntheses or guidelines pooled it, 39 citations in OpenAlex.
- KASL clinical practice guidelines for management of autoimmune hepatitis 2022.Clinical and molecular hepatology · 2023Guideline
- Association between the c.415C > T, c.52G > A, and 36_37insGGAGTC polymorphisms ofDrug design, development and therapy · 2019Pooled it
- Pharmacogenomics of Thiopurine Drugs: A Bench-To-Bedside Success Story in Thailand.Clinical and translational science · 2026Review
- The frequency ofFrontiers in oncology · 2024Article
- A Simple, Rapid, and Cost-Effective PCR Procedure for Detection ofJournal of laboratory physicians · 2023Article
- Precision medicine in inflammatory bowel disease.Precision clinical medicine · 2023Review
- [Treatment of Autoimmune Hepatitis].The Korean journal of gastroenterology = Taehan Sohwagi Hakhoe chi · 2023Review
- Clinical utility of thiopurine metabolite monitoring in inflammatory bowel disease and its impact on healthcare utilization in Singapore.JGH open : an open access journal of gastroenterology and hepatology · 2022Article
- Nudix Hydroxylase 15 Mutations Strongly Predict Thiopurine-Induced Leukopenia Across Different Asian Ethnicities: Implications for Screening in a Diverse Population.Frontiers in medicine · 2022Article
- Cost-effectiveness analysis of genotype screening and therapeutic drug monitoring in patients with inflammatory bowel disease treated with azathioprine therapy: a Chinese healthcare perspective using real-world data.Annals of translational medicine · 2021Article
- An international retrospective study for tolerability of 6-mercaptopurine on NUDT15 bi-allelic variants in children with acute lymphoblastic leukemia.Haematologica · 2021Article
- Association of genetic variants in TPMT, ITPA, and NUDT15 with azathioprine-induced myelosuppression in southwest china patients with autoimmune hepatitis.Scientific reports · 2021Article
- Genetic Polymorphisms of Drug-Metabolizing Enzymes Involved in 6-Mercaptopurine-Induced Myelosuppression in Thai Pediatric Acute Lymphoblastic Leukemia Patients.Journal of pediatric genetics · 2021Article
- Childhood acute lymphoblastic leukemia mercaptopurine intolerance is associated with NUDT15 variants.Pediatric research · 2021Article
- Meta-Analysis ofFrontiers in pharmacology · 2021Review
- NUDT15 gene variants and thiopurine-induced leukopenia in patients with inflammatory bowel disease.Intestinal research · 2020Review
- An intronic FTO variant rs16952570 confers protection against thiopurine-induced myelotoxicities in multiethnic Asian IBD patients.The pharmacogenomics journal · 2020Article
- Predictive Value of NUDT15 Variants on Neutropenia Among Han Chinese Patients with Dermatologic Diseases: A Single-Center Observational Study.Dermatology and therapy · 2020Article
- Identification of NUDT15 gene variants in Amazonian Amerindians and admixed individuals from northern Brazil.PloS one · 2020Article
- Inflammatory Bowel Disease: A Personalized Approach.Frontiers in pediatrics · 2020Article
Corrections and comments
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Authors and funding
15 authors at 7 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundGenetic variants of TPMT and NUDT15 have been reported to predict the inter-patient variability in response and toxicity profiles of patients receiving thiopurine therapy. However, the clinical utility of TPMT genotyping in guiding thiopurine doses has been questionable, in part due to underlying differences in the prevalence of TPMT variants in both Caucasian and Asian populations. Several NUDT15 variants have been associated with thiopurine-induced leukopenia, particularly in Asian cohorts. So far, none have been reported in a multiethnic Asian population.
aimTo investigate the associations between TPMT and NUDT15 variants with thiopurine-induced myelotoxicity in 129 Asian inflammatory bowel disease patients. MATERIALS &
methodsPyrosequencing was performed to screen for TPMT and NUDT15 variants. Intracellular steady-state metabolite concentrations were quantified using liquid chromatography-tandem mass spectrometry.
resultsSignificant declines in nadir white blood cell, absolute neutrophil count and platelet counts were observed with increasing copy numbers of the risk T allele at NUDT15 c.415C>T locus (overall p < 0.05) within 4, 8 and 12 weeks and 6 months after thiopurine initiation. Patients with low and intermediate NUDT15 activity, as inferred from haplotype pairs, had significantly higher risks of leukopenia (p = 0.000253) and neutropenia (p = 0.002) compared with patients with normal NUDT15 activity.
conclusionThese findings highlight the critical relevance of NUDT15 pharmacogenetics in predicting for thiopurine-induced myelotoxicity and confirm the lack of significance of TPMT variants in Asian inflammatory bowel disease patients.
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