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

dc.creatorEl-Jaick, Kenia Balbi
dc.creatorRibeiro-Alves, Marcelo
dc.creatorSoares, Marcos Vinícius Guimarães
dc.creatorAraujo, Gabriela Eduardo França de
dc.creatorPereira, Gabriel Rodrigues Coutinho
dc.creatorRolla, Valeria Cavalcanti
dc.creatorMesquita, Joelma Freire de
dc.creatorCastro, Liane de
dc.date2022-05-25T20:14:56Z
dc.date2022-05-25T20:14:56Z
dc.date2022
dc.date.accessioned2023-09-26T20:50:24Z
dc.date.available2023-09-26T20:50:24Z
dc.identifierEL-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.identifier0074-0276
dc.identifierhttps://www.arca.fiocruz.br/handle/icict/52892
dc.identifier10.1590/0074-02760210328
dc.identifier.urihttps://repositorioslatinoamericanos.uchile.cl/handle/2250/8864800
dc.descriptionBackground: 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.
dc.formatapplication/pdf
dc.languageeng
dc.publisherFiocruz/IOC
dc.rightsopen access
dc.subjectArylamine N acetyltransferase 2
dc.subjectrs1801280
dc.subjectChemically induced liver toxicity
dc.subjectLiver injury
dc.subjectToxic hepatitis
dc.subjectPrecision medicine
dc.titleHomozygotes NAT2*5B slow acetylators are highly associated with hepatotoxicity induced by anti-tuberculosis drugs
dc.typeArticle


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