Genetic Variations Associated with Anti-Tuberculosis Drug-Induced Liver Injury.
Genetic Variations Associated with Anti-Tuberculosis Drug-Induced Liver Injury.
复制标题
DOI：
10.1007/s40495-018-0131-8
复制
发表时间：
2018-06
影响因子：
--
通讯作者：
Zhong XB
中科院分区：
文献类型：
--
作者：
Bao Y;Ma X;Rasmussen TP;Zhong XB
为了对抗耐药性的发展，结核病的临床治疗需要联合使用多种抗结核（抗TB）药物，包括异烟肼和利福平。联合治疗方法是世界卫生组织（WHO）提出的，在全世界得到广泛接受。不幸的是，治疗的主要副作用是抗结核药物诱导的肝损伤（AT-DILI）的发展。许多因素导致异烟肼和利福平介导的AT-DILI，遗传变异是最常见的因素。本综述的目的是提供与异烟肼和利福平介导的AT-DILI相关的遗传变异信息。已在以下途径中编码蛋白质的基因内或附近的基因组区域中确定了与AT-DILI相关的遗传变异：药物代谢酶（NAT 2、CYP 2 E1和GST）、胆汁酸、脂质和血红素代谢产物（CYP 7A 1、BSEP、UGT和PXR）蓄积、免疫适应（HLA和TNF-α）和氧化剂激发（TXNRD 1、SOD 1、BACH 1和MAFK）。本综述中总结的信息考虑了导致AT-DILI的危险因素的遗传基础，并为未来的研究提供了可能有助于的信息。一些涉及的遗传变异可用于设计基因检测，并作为生物标志物，用于预测个体化用药中异烟肼和利福平介导的AT-DILI风险。
In order to combat the development of drug resistance, the clinical treatment of tuberculosis requires the combined use of several anti-tuberculosis (anti-TB) drugs, including isoniazid and rifampicin. Combinational treatment approaches are suggested by the World Health Organization (WHO) and are widely accepted throughout the world. Unfortunately, a major side effect of the treatment is the development of anti-tuberculosis drug-induced liver injury (AT-DILI). Many factors contribute to isoniazid- and rifampicin-mediated AT-DILI and genetic variations are among the most common factors. The purpose of this review is to provide information on genetic variations associated with isoniazid- and rifampicin-mediated AT-DILI. The genetic variations associated with AT-DILI have been identified in the genomic regions within or near genes encoding proteins in the following pathways: drug metabolizing enzymes (NAT2, CYP2E1, and GSTs), accumulation of bile acids, lipids, and heme metabolites (CYP7A1, BSEP, UGTs, and PXR), immune adaptation (HLAs and TNF-α), and oxidant challenge (TXNRD1, SOD1, BACH1, and MAFK). The information summarized in this review considers the genetic bases of risk factors contributing to AT-DILI and provides information that may help for future studies. Some of the implicated genetic variations can be used in the design of genetic tests and serve as biomarkers for the prediction of isoniazid- and rifampicin-mediated AT-DILI risk in personalized medicine.