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Abstract：
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.
摘要：
抗结核药物引起的肝毒性(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易感性的关联，已经获得了矛盾的结果。因此,我们的目标是使用系统综述/荟萃分析方法评估相关性.PubMed,Medline,科克伦图书馆,从开始到2020年6月10日，搜索了WebofScience和SinoMed数据库中所有符合条件的研究。使用具有95％置信区间（CI）的集合调整后比值比（OR）来评估NR1I2多态性与ATDH风险之间的关联强度。按原产地进行亚组分析，并进行meta回归以检测异质性的潜在来源。总共确定了五项病例对照研究，涉及572例病例和1867例对照。已经报道了NR1I2基因中的14个SNPs,研究最多的SNP是rs3814055和rs7643645。合并的估计没有表现出SNPsrs3814055和rs7643645与ATDH风险之间的任何显著关联(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）。亚组分析在中国患者中获得了相似的阴性结果，ATDH的诊断标准可能是异质性的来源。根据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易感性之间的任何关联.然而,由于研究数量较少,样本量相对较小,因此应谨慎解释这一结论.
