| Journal: | Memorias do Instituto Oswaldo Cruz |
| Database: | PERIÓDICA |
| System number: | 000452410 |
| ISSN: | 0074-0276 |
| Authors: | El-Jaick, Kenia Balbi1 Ribeiro Alves, Marcelo3 Soares, Marcos Vinícius Guimarães2 Araujo, Gabriela Eduardo França de2 Pereira, Gabriel Rodrigues Coutinho2 Rolla, Valeria Cavalcanti3 Mesquita, Joelma Freire De1 De Castro, Liane3 |
| Institutions: | 1Universidade Federal do Estado do Rio de Janeiro, Departamento de Genetica e Biologia Molecular, Rio de Janeiro. Brasil 2Universidade Federal do Estado do Rio de Janeiro, Instituto Biomedico, Rio de Janeiro. Brasil 3Fundacao Oswaldo Cruz, Instituto Nacional de Infectologia Evandro Chagas, Rio de Janeiro. Brasil |
| Year: | 2022 |
| Volumen: | 117 |
| Country: | Brasil |
| Language: | Inglés |
| Document type: | Artículo |
| Approach: | Experimental, aplicado |
| English abstract | BACKGROUND Distinct N-acetyltransferase 2 (NAT2) slow acetylators genotypes have been associated with a higher risk to develop anti-tuberculosis drug-induced hepatotoxicity (DIH). However, studies have not pointed the relevance of different acetylation phenotypes presented by homozygotes and compound heterozygotes slow acetylators on a clinical basis. OBJECTIVES This study aimed to investigate the association between NAT2 genotypes and the risk of developing DIH in Brazilian patients undergoing tuberculosis treatment, focusing on the discrimination of homozygotes and compound heterozygotes slow acetylators. METHODS/FINDINGS The frequency of NAT2 genotypes was analysed by DNA sequencing in 162 patients undergoing tuberculosis therapy. The mutation analyses revealed 15 variants, plus two new NAT2 mutations, that computational simulations predicted to cause structural perturbations in the protein. The multivariate statistical analysis revealed that carriers of NAT2*5/*5 slow acetylator genotype presented a higher risk of developing anti-tuberculosis DIH, on a clinical basis, when compared to the compound heterozygotes presenting NAT2*5 and any other slow acetylator haplotype [aOR 4.97, 95% confidence interval (CI) 1.47-16.82, p = 0.01]. CONCLUSION These findings suggest that patients with TB diagnosis who present the NAT2*5B/*5B genotype should be properly identified and more carefully monitored until treatment outcome in order to prevent the occurrence of anti-tuberculosis DIH |
| Disciplines: | Medicina |
| Keyword: | Farmacología, Hepatotoxicidad, Fármacos antituberculosos, Arilamina N acetiltransferasa 2 |
| Keyword: | Pharmacology, Hepatotoxicity, Antituberculosis agents, Arylamine N acetyltransferase 2 |
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