Genetic Variations Associated with Anti-Tuberculosis Drug-Induced Liver Injury
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Purpose of this Review
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.
KeywordsAnti-tuberculosis drugs Drug-induced liver injury Genetic variations Isoniazid Rifampicin
This work was supported in part by grants from the National Institute of General Medical Sciences [Grant R01GM-118367] (to X.B.Z. and X.M.), the National Institute for Environmental Health Science [Grant R01ES-019487] (to X.B.Z.), the National Institute of Diabetes and Digestive and Kidney Diseases [Grant R01DK-090305] (to X.M.), and the National Institute of Allergy And Infectious Diseases (Grant R01AI-131983) (to X.M.).
Compliance with Ethical Standards
Conflict of Interest
None of the authors has a conflict of interest to declare in relation to this work.
Human and Animal Rights and Informed Consent
This article does not contain any studies with human and animal subjects performed by any of the authors.
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