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Compared to healthy volunteers, tuberculosis patients had significantly reduced <jats:italic>NAT2<\/jats:italic> demethylation index. Compared with non-ATDILI patients, <jats:italic>NAT2<\/jats:italic> demethylation index was significantly decreased in ATDILI patients. An independent association was found between lower <jats:italic>NAT2<\/jats:italic> demethylation index and increased susceptibility to ATDILI. <jats:italic>NAT2<\/jats:italic> demethylation index quantified after starting treatment within 1\u20137\u00a0days was negatively correlated with serum aminotransferases measured within 8\u201360\u00a0days of treatment. ROC curve analysis uncovered that <jats:italic>NAT2<\/jats:italic> 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\u20137\u00a0days. Kaplan\u2013Meier analysis unveiled a notable association between lower <jats:italic>NAT2<\/jats:italic> 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 <jats:italic>NAT2<\/jats:italic> demethylation index could reflect ATDILI progression and potentially be used as a new, specific biomarker for ATDILI.<\/jats:p>","DOI":"10.1038\/s41598-025-95050-6","type":"journal-article","created":{"date-parts":[[2025,3,25]],"date-time":"2025-03-25T05:28:26Z","timestamp":1742880506000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Association of NAT2 promoter hypermethylation with susceptibility to hepatotoxicity due to antituberculosis drugs and biomarker potential"],"prefix":"10.1038","volume":"15","author":[{"given":"Jiraphun","family":"Jittikoon","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wacharapol","family":"Saengsiwaritt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Noppadol","family":"Chanhom","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Usa","family":"Chaikledkaew","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sukanya","family":"Wattanapokayakit","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Surakameth","family":"Mahasirimongkol","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1132-7442","authenticated-orcid":false,"given":"Wanvisa","family":"Udomsinprasert","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,3,25]]},"reference":[{"key":"95050_CR1","doi-asserted-by":"crossref","first-page":"398","DOI":"10.1016\/j.genhosppsych.2013.03.018","volume":"35","author":"AM Doherty","year":"2013","unstructured":"Doherty, A. 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