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Homozygotes NAT2*5B slow acetylators are highly associated with hepatotoxicity induced by anti-tuberculosis drugs
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 compou...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Instituto Oswaldo Cruz, Ministério da Saúde
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9049236/ https://www.ncbi.nlm.nih.gov/pubmed/35588539 http://dx.doi.org/10.1590/0074-02760210328 |
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author | El-Jaick, Kenia Balbi Ribeiro-Alves, Marcelo Soares, Marcos Vinícius Guimarães de Araujo, Gabriela Eduardo França Pereira, Gabriel Rodrigues Coutinho Rolla, Valeria Cavalcanti Mesquita, Joelma Freire De De Castro, Liane |
author_facet | El-Jaick, Kenia Balbi Ribeiro-Alves, Marcelo Soares, Marcos Vinícius Guimarães de Araujo, Gabriela Eduardo França Pereira, Gabriel Rodrigues Coutinho Rolla, Valeria Cavalcanti Mesquita, Joelma Freire De De Castro, Liane |
author_sort | El-Jaick, Kenia Balbi |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-9049236 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Instituto Oswaldo Cruz, Ministério da Saúde |
record_format | MEDLINE/PubMed |
spelling | pubmed-90492362022-05-04 Homozygotes NAT2*5B slow acetylators are highly associated with hepatotoxicity induced by anti-tuberculosis drugs El-Jaick, Kenia Balbi Ribeiro-Alves, Marcelo Soares, Marcos Vinícius Guimarães de Araujo, Gabriela Eduardo França Pereira, Gabriel Rodrigues Coutinho Rolla, Valeria Cavalcanti Mesquita, Joelma Freire De De Castro, Liane Mem Inst Oswaldo Cruz Research Article 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. Instituto Oswaldo Cruz, Ministério da Saúde 2022-04-27 /pmc/articles/PMC9049236/ /pubmed/35588539 http://dx.doi.org/10.1590/0074-02760210328 Text en https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License |
spellingShingle | Research Article El-Jaick, Kenia Balbi Ribeiro-Alves, Marcelo Soares, Marcos Vinícius Guimarães de Araujo, Gabriela Eduardo França Pereira, Gabriel Rodrigues Coutinho Rolla, Valeria Cavalcanti Mesquita, Joelma Freire De De Castro, Liane Homozygotes NAT2*5B slow acetylators are highly associated with hepatotoxicity induced by anti-tuberculosis drugs |
title | Homozygotes NAT2*5B slow acetylators are highly associated with hepatotoxicity induced by anti-tuberculosis drugs |
title_full | Homozygotes NAT2*5B slow acetylators are highly associated with hepatotoxicity induced by anti-tuberculosis drugs |
title_fullStr | Homozygotes NAT2*5B slow acetylators are highly associated with hepatotoxicity induced by anti-tuberculosis drugs |
title_full_unstemmed | Homozygotes NAT2*5B slow acetylators are highly associated with hepatotoxicity induced by anti-tuberculosis drugs |
title_short | Homozygotes NAT2*5B slow acetylators are highly associated with hepatotoxicity induced by anti-tuberculosis drugs |
title_sort | homozygotes nat2*5b slow acetylators are highly associated with hepatotoxicity induced by anti-tuberculosis drugs |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9049236/ https://www.ncbi.nlm.nih.gov/pubmed/35588539 http://dx.doi.org/10.1590/0074-02760210328 |
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