Please use this identifier to cite or link to this item: https://www.arca.fiocruz.br/handle/icict/10902
Title: The role of cigarette smoking and liver enzymes polymorphisms in anti-tuberculosis drug-induced hepatotoxicity in brazilian patients
Authors: Valle, Camila Zaverucha do
Monteiro, Sérgio Pereira
El-Jaick, Kênia Balbi
Rosadas, Leonardo Azevedo da Silva
Costa, Marli Jane Martins
Quintana, Marcel de Souza Borges
Castro, Liane de
Affilliation: Fundação Oswaldo Cruz. Instituto Nacional de Infectologia Evandro Chagas. Laboratório de Pesquisa em Farmacogenética. Rio de Janeiro, RJ, Brasil
Fundação Oswaldo Cruz. Instituto Nacional de Infectologia Evandro Chagas. Laboratório de Genética Humana. Rio de Janeiro, RJ, Brasil
Fundação Oswaldo Cruz. Instituto Nacional de Infectologia Evandro Chagas. Laboratório de Pesquisa em Farmacogenética. Rio de Janeiro, RJ, Brasil / Universidade Federal do Estado do Rio de Janeiro. Departamento de Genética e Biologia Molecular. Rio de Janeiro, RJ, Brasil
Fundação Oswaldo Cruz. Instituto Nacional de Infectologia Evandro Chagas. Laboratório de Pesquisa em Farmacogenética. 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
Fundação Oswaldo Cruz. Instituto Nacional de Infectologia Evandro Chagas. Plataforma de Pesquisa Clínica. Vice-Presidência de Pesquisa. Laboratório de Referência. Rio de Janeiro, RJ, Brasil
Fundação Oswaldo Cruz. Instituto Nacional de Infectologia Evandro Chagas. Laboratório de Pesquisa em Farmacogenética. Rio de Janeiro, RJ, Brasil
Abstract: Tuberculosis (TB) is still a major health concern and side-effects related to the treatment, especially druginduced hepatotoxicity (DIH), should be better investigated. In the present study, a possible association between anti-TB DIH and cigarette smoking, N-acetyltransferase 2 (NAT2), Cytochrome P450 2E1 (CYP2E1) and Cytochrome P450 3A4 (CYP3A4) genotypes was studied in 131 TB Brazilian patients. The NAT2 and CYP3A4 genetic polymorphisms were determined using a polymerase chain reaction (PCR) direct sequencing approach and genetic polymorphisms of CYP2E1 gene were determined by restriction fragment length polymorphism (RFLP). The risk of anti-TB DIH was lower in rapid/intermediate acetylators when compared to slowacetylators (OR: 0.34, CI 95: 0.16e0.71; p < 0.01). A decreased risk of developing anti-TB DIH was also observed in active smokers when compared to non-smokers (OR: 0.28, 95 CI: 0.11e0.64; p < 0.01). Significant association between CYP3A4 genotypes and hepatotoxicity was not observed, as well as between CYP2E1 genotype and hepatotoxicity, whose frequency of patients with wild homozygous was more prevalent. The anti-TB drugs interactions with smoking on hepatotoxicity, as well as the NAT2 phenotype, may require to adjust therapeutic regimen dosages or alarm in case of adverse event developments.
Keywords: Anti-tuberculosis drug
Hepatotoxicity
Liver enzymes
Cigarette smoking
DeCS: Tuberculose
Reação em Cadeia da Polimerase
Polimorfismo de Fragmento de Restrição
Brasil
Issue Date: 2014
Publisher: Elsevier
Citation: VALLE, Camila Zaverucha do et al. The role of cigarette smoking and liver enzymes polymorphisms in anti-tuberculosis drug-induced hepatotoxicity in brazilian patients. Tuberculosis, v.94, n.3, p.299–305, 2014.
DOI: 10.1016/j.tube.2014.03.006
ISSN: 1472-9792
Copyright: restricted access
Appears in Collections:IOC - Artigos de Periódicos
INI - Artigos de Periódicos

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