Zazuli Z, Barliana M I, Mulyani U A, Perwitasari D A, Ng H, Abdulah R
Department of Pharmacology and Clinical Pharmacy, Faculty of Pharmacy, Universitas Padjadjaran, Jatinangor, Indonesia.
Department of Biological Pharmacy, Faculty of Pharmacy, Universitas Padjadjaran, Jatinangor, Indonesia.
J Clin Pharm Ther. 2015 Dec;40(6):680-4. doi: 10.1111/jcpt.12325. Epub 2015 Sep 29.
Tuberculosis is still a major infectious disease in Indonesia. Patients are treated mostly using fixed-dose combination treatment in primary public health facilities. The incidence of antituberculosis drug-induced liver injury (AT-DILI) is approximately 10% among Indonesian tuberculosis patients who used standard fixed combination regimens during the intensive phase of treatment. However, information regarding genetic polymorphism associated with the increase risk of drug-induced liver injury is still limited. The aim of this study was to investigate pregnane X receptor (PXR) gene polymorphisms as one of the risk factors of AT-DILI.
In this prospective cohort study, we recruited 106 adult patients diagnosed with pulmonary tuberculosis and treated with category I FDC (fixed-dose combination). The identification of SNP -25385C>T (rs3814055) was conducted by ARMS (amplification refractory mutation system). Hepatotoxicity was defined as ALT and/or AST levels above the normal threshold on the second, fourth and sixth months of monitoring during tuberculosis treatment.
The logistic regression analysis showed that patients with the TT genotype of PXR gene (rs3814055) significantly had a greater risk of AT-DILI (OR 8·89; 95% CI 1·36-57·93, P < 0·05), compared with those of wild-type CC genotype.
The result suggests that in Indonesian patients with tuberculosis, the risk of having AT-DILI was associated with TT genotype of the PXR gene.
在印度尼西亚，结核病仍是一种主要的传染病。在初级公共卫生机构中，患者大多采用固定剂量联合治疗。在印度尼西亚接受强化期标准固定联合治疗方案的结核病患者中，抗结核药物性肝损伤（AT-DILI）的发生率约为10%。然而，关于与药物性肝损伤风险增加相关的基因多态性的信息仍然有限。本研究的目的是调查孕烷X受体（PXR）基因多态性作为AT-DILI的危险因素之一。
在这项前瞻性队列研究中，我们招募了106名被诊断为肺结核并接受I类固定剂量联合（FDC）治疗的成年患者。通过扩增阻滞突变系统（ARMS）对单核苷酸多态性-25385C>T（rs3814055）进行鉴定。肝毒性定义为在结核病治疗期间监测的第二个、第四个和第六个月时，谷丙转氨酶（ALT）和/或谷草转氨酶（AST）水平高于正常阈值。
逻辑回归分析显示，与野生型CC基因型患者相比，PXR基因（rs3814055）TT基因型患者发生AT-DILI的风险显著更高（比值比8.89；95%置信区间1.36 - 57.93，P < 0.05）。
结果表明，在印度尼西亚结核病患者中，发生AT-DILI的风险与PXR基因的TT基因型有关。
