Scholarlink

Background <p>Anti-tuberculosis drug-induced liver injury (ATLI) is a significant adverse drug reaction with genetic susceptibility implications.</p> Aim <p>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.</p> Method <p>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.</p> Results <p>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) <i>null</i> genotype (OR = 1.43, 95% CI: 1.18–1.73, <i>P</i> &lt; 0.001) and N-acetyltransferase 2 (NAT2) polymorphisms, including <i>rs1799929</i> (dominant model, OR = 1.35, 95% CI: 1.12–1.63, <i>P</i> &lt; 0.001), <i>rs1799930</i> (dominant model, OR = 1.43, 95% CI: 1.23–1.66, <i>P</i> &lt; 0.001), <i>rs1799931</i> (dominant model, OR = 1.22, 95% CI: 1.02–1.46, <i>P</i> = 0.03), and the slow acetylator (SA) phenotype (OR = 2.91, 95% CI: 2.43–3.49, <i>P</i> &lt; 0.001). No significant association was found between the CYP2E1 RsaI/PstI polymorphism (<i>C1/C1</i> genotype) and ATLI risk (dominant model, OR = 0.79, 95% CI: 0.61–1.02, <i>P</i> = 0.08).</p> Conclusion <p>This umbrella review confirms that the GSTM1 <i>null</i> genotype, NAT2 polymorphisms (<i>rs1799929</i>, <i>rs1799930</i>, <i>rs1799931</i>), 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.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

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

  • 期刊论文

  • 发表日期：

    2025年2月15日

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

摘要

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.