GSTT1 and GSTM1 gene deletions are not associated with hepatotoxicity caused by antitubercular drugs.

ABSTRACT

BACKGROUND AND OBJECTIVE: Susceptibility to antitubercular drug (ATD)-induced hepatotoxicity may be genetically mediated, with variant alleles of genes such as N-acetyltransferase (NAT2) and CYP2E1 reported as risk factors. Two studies of Asian populations have reported that GSTM1*0 / *0 (null) genotype was a likely predictor of hepatotoxicity, whereas another of a Caucasian population implicated GSTT1*0 / *0. We undertook a prospective case-control study to investigate whether GSTM*0 / *0 and GSTT1*0 / *0 were risk factors for ATD-induced hepatotoxicity. METHODS: Pulmonary tuberculosis patients on isoniazid, rifampicin and pyrazinamide who developed hepatotoxicity using defined criteria were prospectively identified. These cases were then matched with at least one control subject on the same drugs but without hepatotoxicity. Genotyping for GSTM1 and GSTT1 was performed by multiplex PCR on genomic DNA. The odds ratios for the frequency of specific GSTM1 and GSTT1 homozygotes in the case and control subjects were calculated to test for association between the genotypes and hepatotoxicity. RESULTS AND DISCUSSION: Hundred and fifty-one subjects (51 cases, 100 controls) were enrolled. Odds ratio for GSTM1 null genotype was 1.00 (95% CI 0.51-1.97) and GSTT1 null was 2.02 (95% CI 0.39-10.39), respectively, showing that these genotypes are not associated with hepatotoxicity. CONCLUSION: GSTM1 *0 / *0 or GSTT1 *0 / *0 or both null genotypes, do not appear to be associated with ATD-induced hepatotoxicity in our Indian population.