Are genetic variations in glutathione S-transferases involved in anti-tuberculosis drug-induced liver injury? A meta-analysis.

Abstract

As a crucial protective role in the detoxifying mechanisms of drugs, glutathione S-transferases (GSTs) may affect an individual patient's susceptibility to anti-tuberculosis drug-induced liver injury (ATLI). However, the results of studies investigate the association between GSTM1, GSTT1 and GSTP1 polymorphisms and risk of ATLI are inconclusive. A meta-analysis on this topic was performed. PubMed, EMBASE, ISI web of science and the Chinese National Knowledge Infrastructure (CNKI) were systematically searched to identify relevant studies. Odds ratios (ORs) with corresponding 95% confidence intervals (CIs) were calculated. Heterogeneity among articles and publication bias were also tested. After excluding one study as an outlier, the null GSTM1 genotype was associated with an increased risk of ATLI (OR=1.270, 95% CI (1.014-1.590, P=.038), especially in East Asians (OR=1.501, 95% CI (1.303-1.730). With similar exclusion, the null GSTT1 genotype increased the risk of ATLI in the total population (OR=1.169, 95% CI: 1.028-1.330) and in Indians (OR=1.732, 95% CI: 1.229-2.416). No statistically significant association was observed between the mutant GSTP1 genotype with risk of ATLI, which may need more rigorous and uniform case-control or cohort studies for more robust inferences. This up-to-date meta-analysis strongly suggests associations of GSTM1 and GSTT1 polymorphisms with ATLI. The results show the increased risk of ATL1 with the null GSTM1 and GSTT1 genotype on ATLI development. No such association is shown with the mutant GSTP1 genotype.