Evidence map›Paper›PMID 34467830›Full record

ArticleEmerging microbes & infections2021

Global DNA hypomethylation of Alu and LINE-1 transposable elements as an epigenetic biomarker of anti-tuberculosis drug-induced liver injury.

Wanvisa Udomsinprasert, Wanchaloem Sakuntasri, Jiraphun Jittikoon, Usa Chaikledkaew, Sittisak Honsawek, Wasun Chantratita, Sukanya Wattanapokayakit, Surakameth Mahasirimongkol

Open access · goldAbstract readMulticenter Study
In one paragraph

Article in Emerging microbes & infections, 2021. 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
0.8field-weighted citation impact, top 28% 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, 9 citations in OpenAlex.

  1. Article
  2. Review
  3. Article
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

8 authors at 3 institutions in 2 countries.

Wanvisa UdomsinprasertDepartment of Biochemistry, Faculty of Pharmacy, Mahidol University, Bangkok, Thailand.ORCID 0000-0002-1132-7442
Wanchaloem SakuntasriMaster of Science Program in Biopharmaceutical Sciences, Department of Biochemistry, Faculty of Pharmacy, Mahidol University, Bangkok, Thailand.
Jiraphun JittikoonDepartment of Biochemistry, Faculty of Pharmacy, Mahidol University, Bangkok, Thailand.
Usa ChaikledkaewSocial and Administrative Pharmacy Division, Department of Pharmacy, Faculty of Pharmacy, Mahidol University, Bangkok, Thailand.
Sittisak HonsawekDepartment of Biochemistry, Osteoarthritis and Musculoskeleton Research Unit, Faculty of Medicine, Chulalongkorn University, King Chulalongkorn Memorial Hospital, Thai Red Cross Society, Bangkok, Thailand.
Wasun ChantratitaCenter for Medical Genomics, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand.
Sukanya WattanapokayakitDivision of Genomic Medicine and Innovation Support, Department of Medical Sciences, Ministry of Public Health, Genomic Medicine Centre, Nonthaburi, Thailand.
Surakameth MahasirimongkolDivision of Genomic Medicine and Innovation Support, Department of Medical Sciences, Ministry of Public Health, Genomic Medicine Centre, Nonthaburi, Thailand.
Mahidol University · THMinistry of Public Health · THThai Red Cross Society · TH

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Despite being highly effective, anti-tuberculosis (TB) drugs often induce adverse liver injury, anti-TB drug-induced liver injury (ATDILI), leading to treatment failure given no sensitive and selective ATDILI markers. Herein, we conducted a case-control association study to determine whether global DNA methylation of Alu and LINE-1 transposable elements responsible for genomic stability and transcriptional regulation was correlated with clinical parameters indicating ATDILI in TB patients and might serve as an ATDILI biomarker. Alu and LINE-1 methylation levels in blood leukocyte of 130 TB patients (80 ATDILI cases and 50 non-ATDILI cases) and 100 healthy controls were quantified using quantitative combined bisulfite restriction analysis. Both TB patients with and without ATDILI had significantly lower methylation levels of Alu and LINE-1 elements than healthy controls. Compared with non-ATDILI patients, Alu methylation levels were significantly decreased in ATDILI patients, commensurate with LINE-1 methylation analysis. Hypomethylation of Alu and LINE-1 measured within 1-7 days of TB treatment was independently associated with raised levels of serum aminotransferases assessed within 8-60 days of TB treatment. Receiver operating characteristic curve analysis uncovered that Alu and LINE-1 methylation levels were both more sensitive and specific for differentiating ATDILI cases from non-ATDILI cases than serum aminotransferases after starting TB treatment within 1-7 days. Kaplan-Meier analysis displayed a significant association between hypomethylation of Alu and LINE-1 elements and an increased rate of ATDILI occurrence in TB patients. Collectively, global DNA hypomethylation of Alu and LINE-1 elements would reflect ATDILI progression and might serve as novel sensitive and specific ATDILI biomarkers.

Indexed as

AdultAgedAlu ElementsAntitubercular AgentsCase-Control StudiesChemical and Drug Induced Liver InjuryDNA MethylationDNA Transposable ElementsFemaleGenetic MarkersHumansLeukocytesLiverLong Interspersed Nucleotide ElementsMaleMiddle AgedAntitubercular AgentsDNA Transposable ElementsGenetic MarkersTransaminasesAluanti-tuberculosis drug-induced liver injurybiomarkerglobal DNA methylationLINE-1tuberculosis

Identifiers

PMID34467830
PMCPMC8451674
OpenAlexW3196313408

What OpenQuestion holds

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LicenceCC BY-NC
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Registered trials

None linked

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.