Department of Epidemiology and Biostatistics, School of Public Health, Nanjing Medical University, Nanjing, China.
Department of Criminal Science and Technology, Nanjing Forest Police College, Nanjing, China.
Pharmacol Res Perspect. 2020 Dec;8(6):e00696. doi: 10.1002/prp2.696.
Anti-tuberculosis drug-induced hepatotoxicity (ATDH) is a serious adverse drug reaction. Conflicting results have been obtained regarding the associations of nuclear receptor subfamily 1 group I member 2 (NR1I2) gene polymorphisms on susceptibility to ATDH. Therefore, we aimed to evaluate the associations using a systematic review/meta-analysis approach. PubMed, Medline, Cochrane Library, Web of Science and SinoMed databases were searched for all eligible studies from inception to June 10, 2020. Pooled adjusted odds ratios (ORs) with 95% confidence intervals (CIs) were employed to evaluate the strength of the association between the NR1I2 polymorphisms and the risk of ATDH. Subgroup analysis was performed by region of origin, and meta-regression were performed to detect potential sources of heterogeneity. A total of five case-control studies involving 572 cases and 1867 controls were identified. Fourteen SNPs in the NR1I2 gene have been reported, and the most heavily studied SNPs were rs3814055 and rs7643645. The pooled estimates did not exhibit any significant associations between SNPs rs3814055 and rs7643645 and the risk of ATDH (rs3814055: dominant model, OR = 1.00, 95% CI: 0.82-1.22, P = 1.00; recessive model, OR = 1.17, 95% CI: 0.76-1.78, P = .48; rs7643645: dominant model, OR = 1.04, 95% CI: 0.64-1.68, P = .89; recessive model, OR = 0.98, 95% CI: 0.65-1.49, P = .93). Subgroup analysis obtained similar negative results in Chinese patients, and the diagnostic criteria of ATDH may be the source of heterogeneity. Based on the meta-analysis described in this report, we did not observe any association between NR1I2 gene polymorphisms and ATDH susceptibility. However, this conclusion should be interpreted with caution due to the low number of studies and the relatively small sample size.
抗结核药物性肝损伤（ATDH）是一种严重的药物不良反应。关于核受体亚家族 1 组 I 成员 2（NR1I2）基因多态性与 ATDH 易感性的相关性，已有相互矛盾的结果。因此，我们旨在通过系统评价/荟萃分析方法来评估这些关联。从建库到 2020 年 6 月 10 日，我们检索了 PubMed、Medline、Cochrane 图书馆、Web of Science 和 SinoMed 数据库，以获取所有符合条件的研究。采用合并调整后的比值比（OR）及其 95%置信区间（CI）来评估 NR1I2 多态性与 ATDH 风险之间的关联强度。根据来源地区进行亚组分析，并进行荟萃回归以检测潜在的异质性来源。共纳入了 5 项病例对照研究，涉及 572 例病例和 1867 例对照。NR1I2 基因中已有 14 个 SNP 被报道，其中研究最多的 SNP 是 rs3814055 和 rs7643645。汇总估计显示，rs3814055 和 rs7643645 与 ATDH 风险之间没有显著关联（rs3814055：显性模型，OR=1.00，95%CI：0.82-1.22，P=1.00；隐性模型，OR=1.17，95%CI：0.76-1.78，P=0.48；rs7643645：显性模型，OR=1.04，95%CI：0.64-1.68，P=0.89；隐性模型，OR=0.98，95%CI：0.65-1.49，P=0.93）。在中国患者中进行的亚组分析得到了类似的阴性结果，ATDH 的诊断标准可能是异质性的来源。基于本报告中描述的荟萃分析，我们没有观察到 NR1I2 基因多态性与 ATDH 易感性之间存在任何关联。然而，由于研究数量较少且样本量相对较小，该结论应谨慎解释。
