Evidence map›Paper›PMID 37454061›Full record

ArticleBMC gastroenterology2023

Analysis of the NUDT15 gene and metabolites of azathioprine in Japanese patients with inflammatory bowel disease.

Shizuka Suzuki, Kan Uchiyama, Yutaro Motoi, Yuuki Yoshii, Yukari Inoue, Takahiro Kubota, Shunichi Odahara, Yuichiro Ohtaki, Shinichiro Takami, Zensho Ito and 4 more

Open access · goldAbstract read
In one paragraph

Article in BMC gastroenterology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
0.9field-weighted citation impact, top 25% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

3 citing papers in PubMed, 3 citations in OpenAlex.

  1. Article
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  3. Higher prevalence ofFrontiers in pharmacology · 2025
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

14 authors at 4 institutions in 1 country.

Shizuka Suzuki *Division of Gastroenterology and Hepatology, Department of Internal Medicine, The Jikei University Kashiwa Hospital, 163-1 Kashiwa, Kashiwa-Shi, Chiba, 277-8567, Japan.
Kan Uchiyama *Division of Gastroenterology and Hepatology, Department of Internal Medicine, The Jikei University Kashiwa Hospital, 163-1 Kashiwa, Kashiwa-Shi, Chiba, 277-8567, Japan. uchikan@jikei.ac.jp.
Yutaro MotoiDepartment of Biopharmaceutics, Faculty of Pharmaceutical Sciences, Niigata University of Pharmacy and Applied Life Sciences, F103a, 265-1 Higashijima, Akiha-Ku, Niigata City, 956-8603, Japan.
Yuuki YoshiiDepartment of Biopharmaceutics, Faculty of Pharmaceutical Sciences, Niigata University of Pharmacy and Applied Life Sciences, F103a, 265-1 Higashijima, Akiha-Ku, Niigata City, 956-8603, Japan.
Yukari InoueDepartment of Biopharmaceutics, Faculty of Pharmaceutical Sciences, Niigata University of Pharmacy and Applied Life Sciences, F103a, 265-1 Higashijima, Akiha-Ku, Niigata City, 956-8603, Japan.
Takahiro KubotaDepartment of Biopharmaceutics, Faculty of Pharmaceutical Sciences, Niigata University of Pharmacy and Applied Life Sciences, F103a, 265-1 Higashijima, Akiha-Ku, Niigata City, 956-8603, Japan.
Shunichi OdaharaDivision of Gastroenterology and Hepatology, Department of Internal Medicine, The Jikei University Kashiwa Hospital, 163-1 Kashiwa, Kashiwa-Shi, Chiba, 277-8567, Japan.
Yuichiro OhtakiDivision of Gastroenterology and Hepatology, Department of Internal Medicine, The Jikei University Kashiwa Hospital, 163-1 Kashiwa, Kashiwa-Shi, Chiba, 277-8567, Japan.
Shinichiro TakamiDivision of Gastroenterology and Hepatology, Department of Internal Medicine, The Jikei University Kashiwa Hospital, 163-1 Kashiwa, Kashiwa-Shi, Chiba, 277-8567, Japan.
Zensho ItoDivision of Gastroenterology and Hepatology, Department of Internal Medicine, The Jikei University Kashiwa Hospital, 163-1 Kashiwa, Kashiwa-Shi, Chiba, 277-8567, Japan.
Nobuhiro SatoDepartment of Microbiota Research, Juntendo University Graduate School of Medicine, 3-3-1 Hongo, Ochanomizu KS Building 4F 405 Bunkyo-Ku, Tokyo, 113-0033, Japan.
Toshifumi OhkusaDepartment of Microbiota Research, Juntendo University Graduate School of Medicine, 3-3-1 Hongo, Ochanomizu KS Building 4F 405 Bunkyo-Ku, Tokyo, 113-0033, Japan.
Shigeo KoidoDivision of Gastroenterology and Hepatology, Department of Internal Medicine, The Jikei University Kashiwa Hospital, 163-1 Kashiwa, Kashiwa-Shi, Chiba, 277-8567, Japan.
Masayuki SarutaDivision of Gastroenterology and Hepatology, Department of Internal Medicine, The Jikei University School of Medicine, 3-19-18 Nishishinbashi, Minato-Ku, Tokyo, 105-0003, Japan.
Jikei University Kashiwa hospital · JPNiigata University of Pharmacy and Medical and Life Sciences · JPJuntendo University · JPJikei University School of Medicine · JP

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundThiopurines continue to play an important role in the treatment of inflammatory bowel disease (IBD). It is well known that thiopurines can cause several adverse reactions. Especially, hematopoietic toxicity may lead to severe agranulocytosis. In a previous prospective study, we investigated the relationship between inosine triphosphate pyrophosphatase (ITPA) c.94c > a polymorphism, 6-thioguanine nucleotide (6-TGN) concentration and toxicity.

methodsTo clarify the cause of thiopurine toxicity, we analysed nucleoside disphosphate-linked moiety X-type motif 15 (NUDT15) gene polymorphisms, i.e., R139C, V18I, and V19_V19insGV, and measured 6-mercaptopurines and 6-methylmercaptopurines (6-MMP) using the archived blood samples collected from 49 IBD patients for our previous study.

resultsThe ITPA c.94c > a polymorphism was detected in 19 patients (38.7%, all heterozygous). The R139C polymorphism was found in 10 patients (20.4%, 1 homozygous, 9 heterozygous), V18_V19insGV in 7 patients (14.3%, all heterozygous), and V18I in 2 patients (4.08%, all heterozygous). Although R139C was more strongly associated with leukopenia than c.94c > a, there were no significant correlations with 6-TGN and 6-MMP levels, as for c.94c > a. The leukopenia incidence rates for each gene polymorphism were 0% in those with all wild-type genes, 21.4% for c.94c > a only, 42.9% for NUDT15 polymorphism (s) only, and 80.0% for both polymorphisms.

conclusionsAll cases of leukopenia were associated with ITPA c.94c > a and/or polymorphism of NUDT15 and the risk of developing leukopenia was synergistically increased by ITPA and NUDT15 gene polymorphism. However, there was no association between the level of azathioprine metabolites and these polymorphisms.

Indexed as

AzathioprineInflammatory Bowel DiseasesLeukopeniaPyrophosphatasesEast Asian PeopleHumansMercaptopurineNudix HydrolasesAzathioprineMercaptopurineNudix HydrolasesNUDT15 protein, humanPyrophosphatasesAzathioprineIBDITPANUDT15

Identifiers

PMID37454061
PMCPMC10350251
OpenAlexW4384408153

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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.