GENETIC PREDICTORS OF ISONIASID HEPATOTOXICITY

DOI: https://doi.org/10.29296/24999490-2018-02-04

N.E. Snalina, D.A. Sychev Russian Medical Academy of Continuous Professional Education, Barrikadnaya str., 2/1, Moscow, 125993, Russian Federation Е-mail: [email protected]

Currently, tuberculosis is the second leading cause of death from an infectious agent in the world and an important social and medical-biological problem. The first-line drug isoniazid is one of the most effective antituberculosisdrug, however it has a wide spectrum of adverse effects, including induced liver damage, which can lead to the death of the patient. The wide range of adverse effects is due to the highly toxic metabolic intermediates, and it could be partially predicted by patient genotyping for polymorphisms of genes involved in the drug metabolism and its metabolic products excretion.For the present time several meta-analyzes have confirmed the relationship between the N-acetyltransferase-2 gene acetylation phenotype and the risk of serious adverse effects or early treatment failure. Also in the literature, a scheme for dose correction in accordance with the acetylation profile of the patient (fast or slow acetylator) has been proposed and tested, and results in the significant reduction of the risk for undesirable outcomes.There are data on the relationship of gene polymorphisms and the CpG-island hypermethylation of cytochromes P450 CYP2E1 and CYP2D6, as well as the null type of the glutathione-S-transferase gene GSTM1 with an increased risk of induced liver damage.There are also other genetic variations contributing to the toxicity of antituberculosis drugs, requiring more detailed studies.
Keywords: 
isoniazid, hepatotoxicity, NAT2, pharmacogenetics, tuberculosis, personalized medicine

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