ArticleJournal of gastroenterology2010
The multidrug-resistance protein 4 polymorphism is a new factor accounting for thiopurine sensitivity in Japanese patients with inflammatory bowel disease.
Article in Journal of gastroenterology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers, 1 of them a synthesis that pooled it.
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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.
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Who cites it
42 citing papers in PubMed, 1 synthesis or guideline pooled it, 108 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
- Genes implicated in thiopurine-induced toxicity: Comparing TPMT enzyme activity with clinical phenotype and exome data in a paediatric IBD cohort.Scientific reports · 2016Trial
- Personalized Therapy with Mercaptopurine in Acute Lymphoblastic Leukemia: Current Advances and Challenges.Current treatment options in oncology · 2026Review
- Drug Interaction-Informed Approaches to Inflammatory Bowel Disease Management.Pharmaceutics · 2024Review
- Personalized medicine to implementation science: Thiopurines set for the leap.JGH open : an open access journal of gastroenterology and hepatology · 2022Article
- Predicted expression of genes involved in the thiopurine metabolic pathway and azathioprine discontinuation due to myelotoxicity.Clinical and translational science · 2022Article
- Optimizing thiopurine therapy in children with acute lymphoblastic leukemia: A promising "MINT" sequencing strategy and therapeutic "DNA-TG" monitoring.Frontiers in pharmacology · 2022Review
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- Pharmacogenomics with red cells: a model to study protein variants of drug transporter genes.Vox sanguinis · 2021Review
- Homozygous ofFrontiers in genetics · 2021Article
- Precision medicine for rheumatologists: lessons from the pharmacogenomics of azathioprine.Clinical rheumatology · 2021Review
- Combining clinical and candidate gene data into a risk score for azathioprine-associated leukopenia in routine clinical practice.The pharmacogenomics journal · 2020Article
- Thiopurines' Metabolites and Drug Toxicity: A Meta-Analysis.Journal of clinical medicine · 2020Review
- Role of Multidrug Resistance Proteins in Nonresponders to Immunomodulatory Therapy for Noninfectious Uveitis.Translational vision science & technology · 2020Article
- Clioquinol: To harm or heal.Pharmacology & therapeutics · 2019Review
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- Article
- Article
- 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.Journal of gastroenterology · 2018Article
- APEX1 Polymorphism and Mercaptopurine-Related Early Onset Neutropenia in Pediatric Acute Lymphoblastic Leukemia.Cancer research and treatment · 2018Article
Corrections and comments
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundMultidrug resistance protein 4 (MRP4) functions as an efflux pump of nucleoside monophosphate analogs, such as 6-mercaptopurine (6-MP) and 6-thioguanine nucleotide (6-TGN). A single-nucleotide polymorphism in human MRP4 (rs3765534) dramatically reduces MRP4 function and results in the intracellular accumulation of 6-TGN. In this study, we investigated the association between MRP4 G2269A polymorphism and thiopurine sensitivity in Japanese IBD patients.
methodsDirect sequencing of the MRP4 exon 18 was performed. The TPMT A719G and ITPase C94A polymorphisms were determined by polymerase-chain reaction-restriction fragment length polymorphism analyses.
resultsOf the 279 samples analyzed (44 healthy volunteers and 235 IBD patients), 68 samples showed a heterozygote of MRP4 G2269A and 7 carried a homozygote. The allelic frequency of MRP4 G2269A was 14.7%. In 130 IBD patients treated with azathioprine/6-MP, the white blood cell count was significantly lower in patients with theMRP4 variant alone (n = 26) than in patients with a wild allelotype (n = 74) (P = 0.014) or in patients with the ITPase variant alone (n = 22) (P = 0.0095). The 6-TGN levels were significantly higher in patients with the MRP4 variant alone than in patients with the wild allelotype(P = 0.049). Of the 15 patients who experienced leucopenia (<3 x 10⁹/l), 7 patients carried the MRP4 variant.The odds ratio of carrying the MRP4 variant alone and having leukopenia was 3.30 (95% confidence interval 1.03–10.57, P = 0.036).
conclusionsThese results suggest that MRP4 G2269A might be a new factor accounting for thiopurine sensitivity in Japanese patients with IBD.
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