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GENETIC POLYMORPHISMS OF NAT2, CYP2E1 AND GST ENZYMES AND THE OCCURRENCE OF ANTITUBERCULOSIS DRUG-INDUCED HEPATITIS IN BRAZILIAN TB PATIENTS
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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% (18/82) vs. 9.8% (6/61), odds ratio (OR), 2.86, 95% 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% 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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