Genetic polymorphisms and anti-tuberculosis drug-induced liver injury: an umbrella review of the evidence.

IF 2.6 4区医学 Q2 PHARMACOLOGY & PHARMACY International Journal of Clinical Pharmacy Pub Date : 2025-02-15 DOI:10.1007/s11096-025-01880-9

Jingru Cheng, Jia Zhu, Ruina Chen, Meiling Zhang, Bing Han, Min Zhu, Yiwen He, Honggang Yi, Shaowen Tang

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Abstract

Background: Anti-tuberculosis drug-induced liver injury (ATLI) is a significant adverse drug reaction with genetic susceptibility implications.

Aim: This study aimed to integrate findings from systematic reviews and meta-analyses on genetic polymorphisms associated with ATLI risk, enhance evidence synthesis, and identify susceptibility gene polymorphisms linked to ATLI occurrence.

Method: The protocol was registered in PROSPERO (CRD42024517311). Systematic searches of PubMed, EMBASE, Web of Science, and Cochrane Library databases were conducted to identify eligible studies from inception to February 21, 2024. Two authors independently reviewed eligibility, extracted data, and assessed quality. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to evaluate associations between genetic polymorphisms and ATLI susceptibility.

Results: A total of 25 meta-analyses were included, including 57 single nucleotide polymorphisms (SNPs) in 15 candidate genes. Significant associations were found for the glutathione S-transferase M1 (GSTM1) null genotype (OR = 1.43, 95% CI: 1.18-1.73, P < 0.001) and N-acetyltransferase 2 (NAT2) polymorphisms, including rs1799929 (dominant model, OR = 1.35, 95% CI: 1.12-1.63, P < 0.001), rs1799930 (dominant model, OR = 1.43, 95% CI: 1.23-1.66, P < 0.001), rs1799931 (dominant model, OR = 1.22, 95% CI: 1.02-1.46, P = 0.03), and the slow acetylator (SA) phenotype (OR = 2.91, 95% CI: 2.43-3.49, P < 0.001). No significant association was found between the CYP2E1 RsaI/PstI polymorphism (C1/C1 genotype) and ATLI risk (dominant model, OR = 0.79, 95% CI: 0.61-1.02, P = 0.08).

Conclusion: This umbrella review confirms that the GSTM1 null genotype, NAT2 polymorphisms (rs1799929, rs1799930, rs1799931), and the slow acetylator phenotype are associated with increased ATLI risk. These findings provide a foundation for further research on genotype-guided approaches to mitigating ATLI.

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背景：目的：本研究旨在整合与 ATLI 风险相关的基因多态性的系统综述和荟萃分析结果，加强证据综合，并确定与 ATLI 发生相关的易感基因多态性：该研究方案已在 PROSPERO（CRD42024517311）上注册。对 PubMed、EMBASE、Web of Science 和 Cochrane Library 数据库进行了系统检索，以确定从开始到 2024 年 2 月 21 日期间符合条件的研究。两位作者独立审查了研究资格、提取了数据并评估了质量。使用带有 95% 置信区间 (CI) 的比值比 (OR) 评估基因多态性与 ATLI 易感性之间的关联：共纳入 25 项元分析，包括 15 个候选基因中的 57 个单核苷酸多态性 (SNP)。发现谷胱甘肽 S-转移酶 M1（GSTM1）空基因型有显著关联（OR = 1.43，95% CI：1.18-1.73，P 结论：本综述证实，GSTM1 空基因型、NAT2 多态性（rs1799929、rs1799930、rs1799931）和缓慢乙酰化表型与 ATLI 风险增加有关。这些发现为进一步研究以基因型为指导的减轻 ATLI 的方法奠定了基础。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

International Journal of Clinical Pharmacy PHARMACOLOGY & PHARMACY-

CiteScore

4.10

自引率

8.30%

发文量

131

审稿时长

4-8 weeks

期刊介绍： The International Journal of Clinical Pharmacy (IJCP) offers a platform for articles on research in Clinical Pharmacy, Pharmaceutical Care and related practice-oriented subjects in the pharmaceutical sciences. IJCP is a bi-monthly, international, peer-reviewed journal that publishes original research data, new ideas and discussions on pharmacotherapy and outcome research, clinical pharmacy, pharmacoepidemiology, pharmacoeconomics, the clinical use of medicines, medical devices and laboratory tests, information on medicines and medical devices information, pharmacy services research, medication management, other clinical aspects of pharmacy. IJCP publishes original Research articles, Review articles , Short research reports, Commentaries, book reviews, and Letters to the Editor. International Journal of Clinical Pharmacy is affiliated with the European Society of Clinical Pharmacy (ESCP). ESCP promotes practice and research in Clinical Pharmacy, especially in Europe. The general aim of the society is to advance education, practice and research in Clinical Pharmacy . Until 2010 the journal was called Pharmacy World & Science.