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
Artículo
en Inglés
| 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)
Asunto principal:
Polimorfismo Genético
/
Arilamina N-Acetiltransferasa
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Enfermedad Hepática Inducida por Sustancias y Drogas
/
Glutatión Transferasa
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Isoniazida
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Antituberculosos
Tipo de estudio:
Estudio de etiología
/
Estudio observacional
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Factores de riesgo
Límite:
Adulto
/
Femenino
/
Humanos
/
Masculino
País/Región como asunto:
America del Sur
/
Brasil
Idioma:
Inglés
Revista:
Mem. Inst. Oswaldo Cruz
Asunto de la revista:
Medicina Tropical
/
Parasitología
Año:
2011
Tipo del documento:
Artículo
/
Documento de proyecto
País de afiliación:
Brasil
Institución/País de afiliación:
Fiocruz/BR
/
Universidade Federal do Rio de Janeiro/BR
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