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
Article
Dans Anglais
| 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.
Texte intégral:
Disponible
Indice:
LILAS (Amériques)
Sujet Principal:
Polymorphisme génétique
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Arylamine N-acetyltransferase
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Lésions hépatiques dues aux substances
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Glutathione transferase
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Isoniazide
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Antituberculeux
Type d'étude:
Etude d'étiologie
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Étude observationnelle
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Facteurs de risque
Limites du sujet:
Adulte
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Femelle
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Humains
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Mâle
Pays comme sujet:
Amérique du Sud
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Brésil
langue:
Anglais
Texte intégral:
Mem. Inst. Oswaldo Cruz
Thème du journal:
Médecine tropicale
/
Parasitologie
Année:
2011
Type:
Article
/
descriptif de projet
Pays d'affiliation:
Brésil
Institution/Pays d'affiliation:
Fiocruz/BR
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Universidade Federal do Rio de Janeiro/BR
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