Author:
Moraes-Silva Victória,Alvim Dutra Cecilia,Quinhones P. Lopes Márcia,Noel Suffys Philip,Rezende Santos Adalberto,Magdinier Gomes Harrison,Lima de F. Teixeira Raquel
Abstract
Tuberculosis (TB), mainly caused by Mycobacterium tuberculosis, accounts for 10 million cases worldwide per year, remaining a major problem for public health. The anti-TB drug isoniazid (INH) is recommended by the WHO. Despite of effective drugs, some individuals do not respond to standard treatment that can result in varying degrees of adverse drug reactions. One of the factors related to the variability in individual response to treatment is the presence of polymorphisms in genes encoding drug-metabolizing proteins, which can alter the protein’s activity. The NAT2 gene encodes Arylamine N-acetyltransferase 2 (NAT2), the main enzyme responsible for INH metabolism. Genetic variants found in NAT2 coding region affect N-acetylation. The rate of substrate metabolism defines the phenotype of individuals as fast, intermediate, slow, or ultra-slow acetylators. The slow phenotype has been associated with high risk of hepatotoxicity during TB treatment, and this risk is shown to be greater when an ultra-slow acetylator is identified. Furthermore, fast phenotype could be associated with extensive TB treatment due to greater drug clearance and therefore lower bioavailability of INH. The identification and use of biomarkers for phenotype prediction could minimize unfavorable therapeutic outcomes and optimize the effectiveness of tuberculosis treatment.