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
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引用次数: 0
摘要
特异性药物性肝损伤是一种对药物、草药产品和膳食补充剂潜在的严重不良反应,其遗传易感性已被确认。然而,特定基因中存在的遗传变异并不能完全解释这种情况的发生,这表明还有其他因素参与其中。药物性肝损伤表观遗传特征有助于解释这种疾病背后的遗传调控机制,并可能提供疾病生物标志物。本系统综述旨在分析药物性肝损伤表观遗传风险关联研究的所有可用信息。主要纳入标准是关于特异性药物性肝损伤的人群研究,并对药物性肝损伤与表观遗传调控机制之间的显著风险关联进行分析。在纳入的 7 篇文章中,6 篇侧重于 DNA 甲基化,1 篇侧重于长非编码 RNA。所有研究都是关于抗结核药物引起的肝损伤,并且都来自亚洲。CYP2D6 中的 CpG 位点甲基化(几率比:9.19,95% 置信区间:3.26-25.89,P<0.05):3.26-25.89, P
Epigenetic modifications in drug-induced liver injury: A systematic review.
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.