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
in English
| LILACS
| ID: lil-602055
Responsible library:
BR1.1
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.
Full text:
Available
Collection:
International databases
Health context:
SDG3 - Health and Well-Being
/
Neglected Diseases
Health problem:
Target 3.3: End transmission of communicable diseases
/
Neglected Diseases
/
Tuberculosis
Database:
LILACS
Main subject:
Polymorphism, Genetic
/
Arylamine N-Acetyltransferase
/
Chemical and Drug Induced Liver Injury
/
Glutathione Transferase
/
Isoniazid
/
Antitubercular Agents
Type of study:
Etiology study
/
Observational study
/
Risk factors
Limits:
Adult
/
Female
/
Humans
/
Male
Country/Region as subject:
South America
/
Brazil
Language:
English
Journal:
Mem. Inst. Oswaldo Cruz
Journal subject:
Tropical Medicine
/
Parasitology
Year:
2011
Document type:
Article
/
Project document
Affiliation country:
Brazil
Institution/Affiliation country:
Fiocruz/BR
/
Universidade Federal do Rio de Janeiro/BR