Romina Lorena de Los Santos-Fernández, Antonio Segovia-Zafra, Guillermo Paz-López, Gonzalo Matilla-Cabello, Hao Niu, Ismael Álvarez-Álvarez, Camilla Stephens, Andrés González-Jiménez, M Isabel Lucena, Raúl J Andrade, Inmaculada Medina-Cáliz
{"title":"Epigenetic modifications in drug-induced liver injury: A systematic review.","authors":"Romina Lorena de Los Santos-Fernández, Antonio Segovia-Zafra, Guillermo Paz-López, Gonzalo Matilla-Cabello, Hao Niu, Ismael Álvarez-Álvarez, Camilla Stephens, Andrés González-Jiménez, M Isabel Lucena, Raúl J Andrade, Inmaculada Medina-Cáliz","doi":"10.1002/bcp.70053","DOIUrl":null,"url":null,"abstract":"<p><p>Genetic susceptibility has been identified in idiosyncratic drug-induced liver injury, a potentially severe adverse reaction towards drugs, herbal products and dietary supplements. However, its occurrence cannot be fully explained by the presence of genetic variants in specific genes, suggesting that other factors are involved. Drug-induced liver injury epigenetic signatures could help explain genetic regulatory mechanisms behind this disease and might provide disease biomarkers. This systematic review aims to analyse all available information on epigenetic risk association studies in drug-induced liver injury. The main inclusion criterion was population studies on idiosyncratic drug-induced liver injury with significant risk association analysis between drug-induced liver injury and an epigenetic regulation mechanism. Out of the 7 included articles, 6 focused on DNA methylation and 1 on long noncoding RNA. All of the studies were on antituberculosis drug-induced liver injury and came from Asia. CpG site methylation in the CYP2D6 (odds ratio: 9.19, 95% confidence interval: 3.26-25.89, P < .001) and NAT2 (odds ratio: 8.37, 95% confidence interval: 2.39-29.32, P = .001) promoters conferred the highest risk. Hypomethylation of LINE-1 and Alu transposable elements has potential as antituberculosis drug-induced liver injury biomarkers, showing an area under the curve value of 0.94. To conclude, the studies mainly focused on DNA methylation modifications associated with antituberculosis drug-induced liver injury, with all of them coming from Asia, where tuberculosis is a public health burden. Despite the lack of knowledge in this area, the evidence has shown that DNA methylation alterations in antituberculosis drug-induced liver injury could have potential as a new diagnostic and therapeutic target.</p>","PeriodicalId":9251,"journal":{"name":"British journal of clinical pharmacology","volume":" ","pages":""},"PeriodicalIF":3.1000,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"British journal of clinical pharmacology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1002/bcp.70053","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"PHARMACOLOGY & PHARMACY","Score":null,"Total":0}
引用次数: 0
Abstract
Genetic susceptibility has been identified in idiosyncratic drug-induced liver injury, a potentially severe adverse reaction towards drugs, herbal products and dietary supplements. However, its occurrence cannot be fully explained by the presence of genetic variants in specific genes, suggesting that other factors are involved. Drug-induced liver injury epigenetic signatures could help explain genetic regulatory mechanisms behind this disease and might provide disease biomarkers. This systematic review aims to analyse all available information on epigenetic risk association studies in drug-induced liver injury. The main inclusion criterion was population studies on idiosyncratic drug-induced liver injury with significant risk association analysis between drug-induced liver injury and an epigenetic regulation mechanism. Out of the 7 included articles, 6 focused on DNA methylation and 1 on long noncoding RNA. All of the studies were on antituberculosis drug-induced liver injury and came from Asia. CpG site methylation in the CYP2D6 (odds ratio: 9.19, 95% confidence interval: 3.26-25.89, P < .001) and NAT2 (odds ratio: 8.37, 95% confidence interval: 2.39-29.32, P = .001) promoters conferred the highest risk. Hypomethylation of LINE-1 and Alu transposable elements has potential as antituberculosis drug-induced liver injury biomarkers, showing an area under the curve value of 0.94. To conclude, the studies mainly focused on DNA methylation modifications associated with antituberculosis drug-induced liver injury, with all of them coming from Asia, where tuberculosis is a public health burden. Despite the lack of knowledge in this area, the evidence has shown that DNA methylation alterations in antituberculosis drug-induced liver injury could have potential as a new diagnostic and therapeutic target.
期刊介绍:
Published on behalf of the British Pharmacological Society, the British Journal of Clinical Pharmacology features papers and reports on all aspects of drug action in humans: review articles, mini review articles, original papers, commentaries, editorials and letters. The Journal enjoys a wide readership, bridging the gap between the medical profession, clinical research and the pharmaceutical industry. It also publishes research on new methods, new drugs and new approaches to treatment. The Journal is recognised as one of the leading publications in its field. It is online only, publishes open access research through its OnlineOpen programme and is published monthly.