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Association of slow N-acetyltransferase 2 profile and anti-TB drug-induced hepatotoxicity in patients from Southern Brazil |
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| Authors: | L. G. Possuelo J. A. Castelan T. C. de Brito A. W. Ribeiro P. I. Cafrune P. D. Picon A. R. Santos R. L. F. Teixeira T. S. Gregianini M. H. Hutz M. L. R. Rossetti A. Zaha |
| Affiliation: | 1. Centro de Desenvolvimento Científico e Tecnológico da Funda??o Estadual de Produ??o e Pesquisa em Saúde, 5400, Avenida Ipiranga, Porto Alegre, RS, 90610-000, Brazil 2. Programa de Pós-Gradua??o em Ciências Biológicas: Bioquímica, ICBS, Universidade Federal do Rio Grande do Sul, 2600, Ramiro Barcelos, Porto Alegre, RS, 90035-003, Brazil 3. Programa de Pós-Gradua??o em Genética e Toxicologia Aplicada, Universidade Luterana do Brasil, 8001, Avenida Farroupilha, S?o José (Canoas), RS, 92425-900, Brasil 4. Laboratório Exame, 1040, Joaquim Nabuco, Novo Hamburgo, RS, 93310-002, Brazil 5. Hospital Sanatório Partenon, 3722, Bento Gon?alves, Porto Alegre, RS, 90650-001, Brazil 6. Laboratório de Biologia Molecular Aplicada a Micobactérias, Instituto Oswaldo Cruz, Funda??o Oswaldo Cruz, IOC/Fiocruz, 4365, Avenida Brazil, Manguinhos, Rio de Janeiro, 21040-900, Brazil 7. Laboratório de Genética Humana, Instituto Oswaldo Cruz, Funda??o Oswaldo Cruz, IOC/Fiocruz, 4365, Avenida Brazil, Manguinhos, Rio de Janeiro, 21040-900, Brazil 8. Departamento de Genética, IB, Universidade Federal do Rio Grande do Sul, 9500, Avenida Bento Gon?alves, Prédio 43323, Porto Alegre, RS, 91501-970, Brazil 9. Departamento de Biologia Molecular e Biotecnologia, IB, and Centro de Biotecnologia, Universidade Federal do Rio Grande do Sul, 9500, Avenida Bento Gon?alves, Prédio 43421, Porto Alegre, RS, 91501-70, Brazil |
| Abstract: | Purpose To determine the frequency of N-acetyltransferase 2 (NAT2) polymorphisms, the NAT2 acetylation profile and its relation to the incidence of gastrointestinal adverse drug reactions (ADRs), anti-tuberculosis (TB) drug-induced hepatotoxicity, and the clinical risk factors for hepatotoxicity in a population from Brazil. Methods Two hundred and fifty-four Brazilian TB patients using isoniazid (INH), rifampicin (RMP), and pirazinamide (PZA) were tested in a prospective cohort study. NAT2 genotyping was performed by direct PCR sequencing. The association between gastrointestinal ADRs/hepatotoxicity and the NAT2 profile genotype was evaluated by univariate analysis and multiple logistic regression. Results Of the 254 patients analyzed, 69 (27.2%) were slow acetylators and 185 (72.8%) were fast acetylators. Sixty-five (25.6%) patients were human immunodeficiency virus (HIV)-positive. Thirty-three (13%) and 14 (5.5%) patients developed gastrointestinal ADR and hepatotoxicity, respectively. Of the 14 hepatotoxicity patients, nine (64.3%) were slow acetylators and five (35.7%) were fast acetylators. Sex, age, presence of hepatitis C virus, alcohol abuse, and baseline aminotransferases were not found to be risk factors for hepatotoxicity. However, logistic regression analysis revealed that slow acetylator status and the presence of HIV (p < 0.05) were independent risk factors for hepatotoxicity. Conclusions Our findings show that HIV-positive patients that have the slow acetylation profile are significantly associated with a higher risk of developing hepatotoxicity due to anti-TB drugs. Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users. |
| Keywords: | Genotyping Hepatotoxicity Isoniazid N-acetyltransferase 2 Tuberculosis |
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