Genetic Polymorphisms and Toxicities of First-Line Antituberculosis Drugs: Systematic Review of the Literature

Introduction: Polymorphisms are the main genetic factors associated with toxicities of antituberculosis drugs. This literature review summarizes the polymorphisms of the genes that code for the enzymes of the metabolism of antituberculosis drugs and their transmembrane transporters. Some mechanisms of drug-associated toxicities and strategies for their management have also been described in this review. Methods: The bibliographic searches were exclusively carried out in PubMed, over a period of ten years (2010-2020). The search terms were the words “toxicity + antituberculosis drug + one or two word(s) among the following: polymorphism, genetics, mutation, SNP, HLA or haplotype”. Publications in English or French, relating to the various toxicities associated with first-line anti-tuberculosis drugs (Rifampicin, Isoniazid, Ethambutol and Pyrazinamide) administered to patients with pulmonary tuberculosis, extrapulmonary tuberculosis or co-infected with TB/HIV were included in this review. Duplicates, in vitro, in silico or drug-induced toxicity studies other than antituberculosis drugs and genetic mutations of Mycobacteria strains were not included. Results: The studies selected and included were case reports, cohort studies, original research, systematic reviews and meta-analyses on human subjects of polymorphisms (TXNRD1, SOD2, TYMP) have been suspected but their mechanisms are not yet well understood.