Precision medicine in tuberculosis treatment – a role for pharmacogenetics?

Isoniazid (INH), a key drug in tuberculosis treatment is a well Known cause of drug induced acute liver failure. Variants in genes encoding proteins involved in INH metabolism, cell detoxification processes, bile salt transport and immunoinflammatory response, have been implicated. Identifying risk genotypes may allow personalization of treatment. Objetive of this study was to identify risk factors for susceptibility to INH induced hepatotoxicity by studying clinical parameters and functional genetic variants in six genes, NAT2, CYP2E1, GSTM1, GSTT1, ABCB11 and IL-6, in TB patients. The studied population included 185 tuberculosis patients, 58 females and 127 males, of which 82 were cases, and 103 were controls. All genetic variants were in Hardy-Weinberg equilibrium. Comparing cases and controls, in univariate analysis, NAT2 (slow acethylator genotypes), ABCB11 (rs2287622 CC genotype), IL-6 (rs1800797 AA and AG genotypes), female gender and age > 60 years were considered statistically significant risk factors (p Conclusion: INH-induced hepatotoxicity is a complex phenotype difficult to predict. Though NAT2 genotype is a major factor determining INH plasma concentrations. Prospective studies should help to verify if personalization of INH dosage, might contribute to a more safe INH treatment.