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 polymorphisms genes that code for enzymes metabolism drugs and their transmembrane transporters. Some mechanisms drug-associated strategies management have also been described in this review. Methods: The bibliographic searches were exclusively carried out PubMed, over a period ten years (2010-2020). search terms words “toxicity + drug one or two word(s) among following: polymorphism, genetics, mutation, SNP, HLA haplotype”. Publications English French, relating to various first-line anti-tuberculosis (Rifampicin, Isoniazid, Ethambutol Pyrazinamide) administered patients pulmonary tuberculosis, extrapulmonary tuberculosis co-infected TB/HIV included Duplicates, vitro, silico drug-induced toxicity studies other than mutations Mycobacteria strains not included. Results: selected case reports, cohort studies, original research, systematic reviews meta-analyses on human subjects different ethnic origins. Hepatotoxicity is most common NAT2, CYP2E1, GSTM1 GSTT1 Other forms toxicity, less frequent, occurring certain under concomitant treatment nonsteroidal anti-inflammatory (NSAIDs), antiretrovirals (ARVs), antibiotics antiepileptics identified. Conclusion: concern both metabolic pathways (NAT2, GST) transporters (SLCO1B1 ABCB1). (TXNRD1, SOD2, TYMP) suspected but yet well understood.