Homozygotes NAT2*5B slow acetylators are highly associated with hepatotoxicity induced by anti-tuberculosis drugs

Detalhes bibliográficos
Autor(a) principal: El-Jaick, Kenia Balbi
Data de Publicação: 2022
Outros Autores: Ribeiro-Alves, Marcelo, Soares, Marcos Vinícius Guimarães, Araujo, Gabriela Eduardo França de, Pereira, Gabriel Rodrigues Coutinho, Rolla, Valeria Cavalcanti, Mesquita, Joelma Freire de, Castro, Liane de
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Institucional da FIOCRUZ (ARCA)
Texto Completo: https://www.arca.fiocruz.br/handle/icict/52892
Resumo: Universidade Federal do Estado do Rio de Janeiro. Departamento de Genética e Biologia Molecular. Rio de Janeiro, RJ, Brasil / Universidade Federal do Estado do Rio de Janeiro. Instituto Biomédico. Programa de Pós-Graduação em Biologia Molecular e Celular. Rio de Janeiro, RJ, Brasil.
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spelling El-Jaick, Kenia BalbiRibeiro-Alves, MarceloSoares, Marcos Vinícius GuimarãesAraujo, Gabriela Eduardo França dePereira, Gabriel Rodrigues CoutinhoRolla, Valeria CavalcantiMesquita, Joelma Freire deCastro, Liane de2022-05-25T20:14:56Z2022-05-25T20:14:56Z2022EL-JAICK, Kenia Balbi et al. Homozygotes NAT2*5B slow acetylators are highly associated with hepatotoxicity induced by anti-tuberculosis drugs. Memorias do Instituto Oswaldo Cruz, Rio de Janeiro, v. 117, p. 1-13, 2022.0074-0276https://www.arca.fiocruz.br/handle/icict/5289210.1590/0074-02760210328engFiocruz/IOCHomozygotes NAT2*5B slow acetylators are highly associated with hepatotoxicity induced by anti-tuberculosis drugsinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleUniversidade Federal do Estado do Rio de Janeiro. Departamento de Genética e Biologia Molecular. Rio de Janeiro, RJ, Brasil / Universidade Federal do Estado do Rio de Janeiro. Instituto Biomédico. Programa de Pós-Graduação em Biologia Molecular e Celular. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Nacional de Infectologia Evandro Chagas. Laboratório de Pesquisa Clínica em DST/AIDS. Rio de Janeiro, RJ, Brasil.Universidade Federal do Estado do Rio de Janeiro. Instituto Biomédico. Programa de Pós-Graduação em Biologia Molecular e Celular. Rio de Janeiro, RJ, Brasil.Universidade Federal do Estado do Rio de Janeiro. Instituto Biomédico. Programa de Pós-Graduação em Biologia Molecular e Celular. Rio de Janeiro, RJ, Brasil.Universidade Federal do Estado do Rio de Janeiro. Instituto Biomédico. Programa de Pós-Graduação em Biologia Molecular e Celular. Rio de Janeiro, RJ, Brasil / Universidade Federal do Estado do Rio de Janeiro. Departamento de Genética e Biologia Molecular. Grupo de Bioinformática e Biologia Computacional. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Nacional de Infectologia Evandro Chagas. Laboratório de Pesquisa Clínica em Micobacterioses. Rio de Janeiro, RJ, Brasil.Universidade Federal do Estado do Rio de Janeiro. Departamento de Genética e Biologia Molecular. Rio de Janeiro, RJ, Brasil / Universidade Federal do Estado do Rio de Janeiro. Instituto Biomédico. Programa de Pós-Graduação em Biologia Molecular e Celular. Rio de Janeiro, RJ, Brasil / Universidade Federal do Estado do Rio de Janeiro. Departamento de Genética e Biologia Molecular. Grupo de Bioinformática e Biologia Computacional. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Nacional de Infectologia Evandro Chagas. Laboratório de Pesquisa em Farmacogenética. Rio de Janeiro, RJ, Brasil.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.Arylamine N acetyltransferase 2rs1801280Chemically induced liver toxicityLiver injuryToxic hepatitisPrecision medicineinfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da FIOCRUZ (ARCA)instname:Fundação Oswaldo Cruz (FIOCRUZ)instacron:FIOCRUZLICENSElicense.txtlicense.txttext/plain; charset=utf-83099https://www.arca.fiocruz.br/bitstream/icict/52892/1/license.txt586c046dcfeef936e32f0323bb9a47c0MD51ORIGINALHomozygotes_Marcelo_Alves_etal_INI_2022.pdfHomozygotes_Marcelo_Alves_etal_INI_2022.pdfapplication/pdf1355496https://www.arca.fiocruz.br/bitstream/icict/52892/2/Homozygotes_Marcelo_Alves_etal_INI_2022.pdf777288b76a75ac502e3af6156d1e56e6MD52icict/528922023-04-30 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dc.title.pt_BR.fl_str_mv 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
spellingShingle Homozygotes NAT2*5B slow acetylators are highly associated with hepatotoxicity induced by anti-tuberculosis drugs
El-Jaick, Kenia Balbi
Arylamine N acetyltransferase 2
rs1801280
Chemically induced liver toxicity
Liver injury
Toxic hepatitis
Precision medicine
title_short 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_sort Homozygotes NAT2*5B slow acetylators are highly associated with hepatotoxicity induced by anti-tuberculosis drugs
author El-Jaick, Kenia Balbi
author_facet El-Jaick, Kenia Balbi
Ribeiro-Alves, Marcelo
Soares, Marcos Vinícius Guimarães
Araujo, Gabriela Eduardo França de
Pereira, Gabriel Rodrigues Coutinho
Rolla, Valeria Cavalcanti
Mesquita, Joelma Freire de
Castro, Liane de
author_role author
author2 Ribeiro-Alves, Marcelo
Soares, Marcos Vinícius Guimarães
Araujo, Gabriela Eduardo França de
Pereira, Gabriel Rodrigues Coutinho
Rolla, Valeria Cavalcanti
Mesquita, Joelma Freire de
Castro, Liane de
author2_role author
author
author
author
author
author
author
dc.contributor.author.fl_str_mv El-Jaick, Kenia Balbi
Ribeiro-Alves, Marcelo
Soares, Marcos Vinícius Guimarães
Araujo, Gabriela Eduardo França de
Pereira, Gabriel Rodrigues Coutinho
Rolla, Valeria Cavalcanti
Mesquita, Joelma Freire de
Castro, Liane de
dc.subject.en.pt_BR.fl_str_mv Arylamine N acetyltransferase 2
rs1801280
Chemically induced liver toxicity
Liver injury
Toxic hepatitis
Precision medicine
topic Arylamine N acetyltransferase 2
rs1801280
Chemically induced liver toxicity
Liver injury
Toxic hepatitis
Precision medicine
description Universidade Federal do Estado do Rio de Janeiro. Departamento de Genética e Biologia Molecular. Rio de Janeiro, RJ, Brasil / Universidade Federal do Estado do Rio de Janeiro. Instituto Biomédico. Programa de Pós-Graduação em Biologia Molecular e Celular. Rio de Janeiro, RJ, Brasil.
publishDate 2022
dc.date.accessioned.fl_str_mv 2022-05-25T20:14:56Z
dc.date.available.fl_str_mv 2022-05-25T20:14:56Z
dc.date.issued.fl_str_mv 2022
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
format article
status_str publishedVersion
dc.identifier.citation.fl_str_mv EL-JAICK, Kenia Balbi et al. Homozygotes NAT2*5B slow acetylators are highly associated with hepatotoxicity induced by anti-tuberculosis drugs. Memorias do Instituto Oswaldo Cruz, Rio de Janeiro, v. 117, p. 1-13, 2022.
dc.identifier.uri.fl_str_mv https://www.arca.fiocruz.br/handle/icict/52892
dc.identifier.issn.pt_BR.fl_str_mv 0074-0276
dc.identifier.doi.none.fl_str_mv 10.1590/0074-02760210328
identifier_str_mv EL-JAICK, Kenia Balbi et al. Homozygotes NAT2*5B slow acetylators are highly associated with hepatotoxicity induced by anti-tuberculosis drugs. Memorias do Instituto Oswaldo Cruz, Rio de Janeiro, v. 117, p. 1-13, 2022.
0074-0276
10.1590/0074-02760210328
url https://www.arca.fiocruz.br/handle/icict/52892
dc.language.iso.fl_str_mv eng
language eng
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv Fiocruz/IOC
publisher.none.fl_str_mv Fiocruz/IOC
dc.source.none.fl_str_mv reponame:Repositório Institucional da FIOCRUZ (ARCA)
instname:Fundação Oswaldo Cruz (FIOCRUZ)
instacron:FIOCRUZ
instname_str Fundação Oswaldo Cruz (FIOCRUZ)
instacron_str FIOCRUZ
institution FIOCRUZ
reponame_str Repositório Institucional da FIOCRUZ (ARCA)
collection Repositório Institucional da FIOCRUZ (ARCA)
bitstream.url.fl_str_mv https://www.arca.fiocruz.br/bitstream/icict/52892/1/license.txt
https://www.arca.fiocruz.br/bitstream/icict/52892/2/Homozygotes_Marcelo_Alves_etal_INI_2022.pdf
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