Genetic polymorphisms of NAT2, CYP2E1 and GST enzymes and the occurrence of antituberculosis drug-induced hepatitis in Brazilian TB patients

Memórias do Instituto Oswaldo Cruz

Raquel Lima De Figueiredo Teixeira²  Renata Gomes Morato²  Pedro Hernan Cabello²  Ligia Mayumi Kitada Muniz¹  Adriana Da Silva Rezende Moreira¹  Afrânio Lineu Kritski¹  Fernanda Carvalho Queiroz Mello¹  Philip Noel Suffys¹  Antonio Basilio De Miranda¹  Adalberto Rezende Santos¹ 

[1] ,Universidade Federal do Rio de Janeiro Faculdade de Medicina Laboratório de Genética HumanaRio de Janeiro RJ ,Brasil

关键词: hepatotoxicity;    tuberculosis;    isoniazid;    NAT2;    CYP2E1;    GSTM1;    GSTT1;   

DOI  :  10.1590/S0074-02762011000600011

来源: SciELO

【 摘 要 】

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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