Genetic polymorphisms of NAT2, CYP2E1 and GST enzymes and the occurrence of antituberculosis drug-induced hepatitis in Brazilian TB patients
Mem. Inst. Oswaldo Cruz
;
106(6): 716-724, Sept. 2011. ilus, tab
Artigo
em Inglês
| LILACS
| ID: lil-602055
ABSTRACT
Isoniazid (INH), one of the most important drugs used in antituberculosis (anti-TB) treatment, is also the major drug involved in hepatotoxicity. Differences in INH-induced toxicity have been attributed to genetic variability at several loci, such as NAT2, CYP2E1, GSTM1 and GSTT1, that code for drug-metabolising enzymes. Our goal was to examine the polymorphisms in these enzymes as susceptibility factors to anti-TB drug-induced hepatitis in Brazilian individuals. In a case-control design, 167 unrelated active tuberculosis patients from the University Hospital of the Federal University of Rio de Janeiro, Brazil, were enrolled in this study. Patients with a history of anti-TB drug-induced acute hepatitis (cases with an increase to 3 times the upper limit of normal serum transaminases and symptoms of hepatitis) and patients with no evidence of anti-TB hepatic side effects (controls) were genotyped for NAT2, CYP2E1, GSTM1 and GSTT1 polymorphisms. Slow acetylators had a higher incidence of hepatitis than intermediate/rapid acetylators [22 percent (18/82) vs. 9.8 percent (6/61), odds ratio (OR), 2.86, 95 percent confidence interval (CI), 1.06-7.68, p = 0.04). Logistic regression showed that slow acetylation status was the only independent risk factor (OR 3.59, 95 percent CI, 2.53-4.64, p = 0.02) for the occurrence of anti-TB drug-induced hepatitis during anti-TB treatment with INH-containing schemes in Brazilian individuals.
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Índice:
LILACS (Américas)
Assunto principal:
Polimorfismo Genético
/
Arilamina N-Acetiltransferase
/
Doença Hepática Induzida por Substâncias e Drogas
/
Glutationa Transferase
/
Isoniazida
/
Antituberculosos
Tipo de estudo:
Estudo de etiologia
/
Estudo observacional
/
Fatores de risco
Limite:
Adulto
/
Feminino
/
Humanos
/
Masculino
País/Região como assunto:
América do Sul
/
Brasil
Idioma:
Inglês
Revista:
Mem. Inst. Oswaldo Cruz
Assunto da revista:
Medicina Tropical
/
Parasitologia
Ano de publicação:
2011
Tipo de documento:
Artigo
/
Documento de projeto
País de afiliação:
Brasil
Instituição/País de afiliação:
Fiocruz/BR
/
Universidade Federal do Rio de Janeiro/BR
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