NAT2 variants are associated with drug-induced liver injury caused by anti-tuberculosis drugs in Indonesian patients with tuberculosis

Drug-induced liver injury (dili) is the most common adverse drug reaction in the treatment of tuberculosis (tb). several studies showed that patients with tb and the slow-acetylator phenotype caused by nat2 variants are highly susceptible to dili caused by anti-tb drugs, hereafter designated at-dili. however, the role of nat2 variants in at-dili has never been assessed for an indonesian population. we recruited 50 patients with tb and at-dili and 191 patients with tb but without at-dili; we then used direct dna sequencing to assess single-nucleotide polymorphisms in the coding region of nat2. nat2*6a was significantly associated with susceptibility to at-dili (p=7.7 × 10−4, odds ratio (or)=4.75 (1.8–12.55)). moreover, patients with tb and the nat2-associated slow-acetylator phenotype showed higher risk of at-dili than patients with the rapid- or intermediate-acetylator phenotypes (p=1.7 × 10−4, or=3.45 (1.79–6.67)). in conclusion, this study confirms the significance of the association between slow-acetylator nat2 variants and susceptibility to at-dili in an indonesian population.