Evidence mapPaperPMID 40133601Full record

ArticleScientific reports2025

Association of NAT2 promoter hypermethylation with susceptibility to hepatotoxicity due to antituberculosis drugs and biomarker potential.

Jiraphun Jittikoon, Wacharapol Saengsiwaritt, Noppadol Chanhom, Usa Chaikledkaew, Sukanya Wattanapokayakit, Surakameth Mahasirimongkol, Wanvisa Udomsinprasert

Abstract read
In one paragraph

Article in Scientific reports, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
field-weighted citation impact
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

1 citing paper in PubMed.

  1. Clinical Medicine Insights. Oncology · 2025
    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

7 authors.

Jiraphun JittikoonDepartment of Biochemistry, Faculty of Pharmacy, Mahidol University, 447 Sri-Ayudthaya Road, Rajathevi, Bangkok, 10400, Thailand.
Wacharapol SaengsiwarittDepartment of Biochemistry, Faculty of Pharmacy, Mahidol University, 447 Sri-Ayudthaya Road, Rajathevi, Bangkok, 10400, Thailand.
Noppadol ChanhomDepartment of Biochemistry, Faculty of Pharmacy, Mahidol University, 447 Sri-Ayudthaya Road, Rajathevi, Bangkok, 10400, Thailand.
Usa ChaikledkaewSocial and Administrative Pharmacy Division, Department of Pharmacy, Faculty of Pharmacy, Mahidol University, Bangkok, 10400, Thailand.
Sukanya WattanapokayakitDivision of Genomic Medicine and Innovation Support, Department of Medical Sciences, Genomic Medicine Centre, Ministry of Public Health, Nonthaburi, 11000, Thailand.
Surakameth MahasirimongkolDivision of Genomic Medicine and Innovation Support, Department of Medical Sciences, Genomic Medicine Centre, Ministry of Public Health, Nonthaburi, 11000, Thailand.
Wanvisa UdomsinprasertDepartment of Biochemistry, Faculty of Pharmacy, Mahidol University, 447 Sri-Ayudthaya Road, Rajathevi, Bangkok, 10400, Thailand. wanvisa.udo@mahidol.ac.th.ORCID http://orcid.org/0000-0002-1132-7442

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

This study aimed to determine whether promoter methylation of N-acetyltransferase 2 (NAT2), a metabolic enzyme responsible for drug metabolism and detoxification, was correlated with clinical parameters indicating anti-tuberculosis drug-induced liver injury (ATDILI) in tuberculosis patients and might emerge as an ATDILI biomarker. NAT2 promoter methylation in blood leukocyte of 102 tuberculosis patients (49 ATDILI cases and 53 non-ATDILI cases) and 100 healthy controls were quantified using quantitative real-time methylation-specific polymerase chain reaction. Compared to healthy volunteers, tuberculosis patients had significantly reduced NAT2 demethylation index. Compared with non-ATDILI patients, NAT2 demethylation index was significantly decreased in ATDILI patients. An independent association was found between lower NAT2 demethylation index and increased susceptibility to ATDILI. NAT2 demethylation index quantified after starting treatment within 1-7 days was negatively correlated with serum aminotransferases measured within 8-60 days of treatment. ROC curve analysis uncovered that NAT2 demethylation index was found to be a more sensitive and specific biomarker for ATDILI when compared to serum aminotransferases measured following treatment initiation within 1-7 days. Kaplan-Meier analysis unveiled a notable association between lower NAT2 demethylation index and a higher incidence of ATDILI in tuberculosis patients, as confirmed by Cox regression analysis while accounting for confounding variables. A reduction in NAT2 demethylation index could reflect ATDILI progression and potentially be used as a new, specific biomarker for ATDILI.

Indexed as

Antitubercular AgentsArylamine N-AcetyltransferaseChemical and Drug Induced Liver InjuryDNA MethylationPromoter Regions, GeneticTuberculosisAdultBiomarkersCase-Control StudiesFemaleHumansMaleMiddle AgedAntitubercular AgentsArylamine N-AcetyltransferaseBiomarkersNAT2 protein, humanAnti-tuberculosis drug-induced liver injuryBiomarkerN-Acetyltransferase 2 (NAT2)Promoter methylationTuberculosis

Identifiers

PMID40133601
PMCPMC11937569

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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 Socratic graph.