Evidence map›Paper›PMID 24762746›Full record

ArticlePloS one2014

New genetic biomarkers predicting azathioprine blood concentrations in combination therapy with 5-aminosalicylic acid.

Kazuhiko Uchiyama, Tomohisa Takagi, Yasunori Iwamoto, Norihiko Kondo, Tetsuya Okayama, Naohisa Yoshida, Kazuhiro Kamada, Kazuhiro Katada, Osamu Handa, Takeshi Ishikawa and 6 more

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
1.0field-weighted citation impact, top 20% 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

2 citing papers in PubMed, 10 citations in OpenAlex.

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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

16 authors at 1 institution in 1 country.

Kazuhiko UchiyamaDepartment of Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, Kyoto, Japan.
Tomohisa TakagiDepartment of Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, Kyoto, Japan.
Yasunori IwamotoDepartment of Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, Kyoto, Japan.
Norihiko KondoDepartment of Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, Kyoto, Japan.
Tetsuya OkayamaDepartment of Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, Kyoto, Japan.
Naohisa YoshidaDepartment of Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, Kyoto, Japan.
Kazuhiro KamadaDepartment of Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, Kyoto, Japan.
Kazuhiro KatadaDepartment of Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, Kyoto, Japan.
Osamu HandaDepartment of Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, Kyoto, Japan.
Takeshi IshikawaDepartment of Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, Kyoto, Japan.
Hiroaki YasudaDepartment of Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, Kyoto, Japan.
Junichi SakagamiDepartment of Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, Kyoto, Japan.
Hideyuki KonishiDepartment of Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, Kyoto, Japan.
Nobuaki YagiDepartment of Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, Kyoto, Japan.
Yuji NaitoDepartment of Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, Kyoto, Japan.
Yoshito ItohDepartment of Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, Kyoto, Japan.
Kyoto Prefectural University of Medicine · JP

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

BACKGROUND AND

aimsAzathioprine (AZA) is widely used for the treatment of inflammatory bowel disease (IBD) patients. AZA is catabolized by thiopurine S-methyltransferase (TPMT), which exhibits genetic polymorphisms. It has also been reported that 5-aminosalicylic acid (5-ASA) inhibits TPMT activity, and that increased 6-thioguanine nucleotide (6-TGN, a metabolite of AZA) blood concentrations result in an increased number of ADRs. In this study, single nucleotide polymorphisms (SNPs) related to differential gene expression affecting AZA drug metabolism in combination therapy with 5-ASA were examined.

methodsTo identify genetic biomarkers for the prediction of 6-TGN blood concentration, ExpressGenotyping analysis was used. ExpressGenotyping analysis is able to detect critical pharmacogenetic SNPs by analyzing drug-induced expression allelic imbalance (EAI) of premature RNA in HapMap lymphocytes. We collected blood samples on 38 patients with inflammatory bowel disease treated with AZA and corroboration of the obtained SNPs was attempted in clinical samples.

resultsA large number of SNPs with AZA/5-ASA-induced EAI within the investigated HapMap lymphocytes was identified by ExpressGenotyping analysis. The respective SNPs were analyzed in IBD patients' blood samples. Among these SNPs, several that have not yet been described to be induced by AZA/5-ASA were found. SNPs within SLC38A9 showed a particular correlation with patients' 6-TGN blood concentrations.

conclusionsBased on these results, ExpressGenotyping analysis and genotyping of patients appears to be a useful way to identify inter-individual differences in drug responses and ADRs to AZA/5-ASA. This study provides helpful information on genetic biomarkers for optimized AZA/5-ASA treatment of IBD patients.

Indexed as

AdultAmino Acid Transport SystemsAnti-Inflammatory Agents, Non-SteroidalAzathioprineCells, CulturedDrug Therapy, CombinationFemaleGenetic Association StudiesGenetic MarkersHumansImmunosuppressive AgentsInflammatory Bowel DiseasesLymphocytesMaleMesalamineMiddle AgedAmino Acid Transport SystemsAnti-Inflammatory Agents, Non-SteroidalAzathioprineGenetic MarkersImmunosuppressive AgentsMesalamineSLC38A9 protein, human

Identifiers

PMID24762746
PMCPMC3999094
OpenAlexW2124017386

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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.