Superoxide Dismutase Gene (SOD1, SOD2, and SOD3) Polymorphisms and Antituberculosis Drug-induced Hepatitis

ciation between GSTT1 and GSTM1 null mutations and ATDinduced hepatitis in Koreans.7 SOD catalyzes the dismutation of superoxide (O2 -) into oxygen and hydrogen peroxide.Thus, SOD serves an important antioxidant defense against oxidative stress.8 Three forms of SOD; namely, cytoplasmic superoxide dismutase (SOD1), mitochondrial superoxide dismutase (SOD2), and extracellular superoxide dismutase (SOD3) are present in mammals.8 Two studies have reported that the SOD2 polymorphism at V16A (C47T) is significantly associated with DILI.6,9 In the present study, we hypothesized that SOD gene (SOD1, SOD2, and SOD3) polymorphisms are associated with ATD-induced hepatitis in a Korean population.Purpose: Drug-induced liver injury (DILI) is a serious issue often leading to discontinuation of the proper regimen of antituberculosis drugs (ATD).Previous studies have suggested that antioxidant enzymes play an important role in DILI.Methods: We explored whether polymorphisms in superoxide dismutase genes, including Cu/Zn superoxide dismutase (SOD1), manganese superoxide dismutase (SOD2) and extracellular superoxide dismutase (SOD3) are associated with ATD-induced hepatitis.Genotype distributions of four single nucleotide polymorphisms (SNPs) in three genes (rs2070424, SOD1; rs4880, SOD2; rs2536512, and rs1799895, SOD3) were compared between 84 patients with ATD-induced hepatitis and 237 patients tolerant to ATD.Results: Intron SNP rs2070424 of SOD1 showed a significant association with ATD-induced hepatitis.The frequency of genotypes carrying minor alleles (GA or GG) was significantly higher in the case group than that of controls (P=0.019,OR=2.26, 95% CI 1.14-4.49).For the other SNPs of SOD2 and SOD3, there were no differences in genotype frequencies between ATD-induced hepatitis and ATD-tolerant controls.Conclusions: These findings suggest that rs2070424 of SOD1 is significantly associated with ATD-induced hepatitis.This genetic variant may be a risk factor for ATD-induced hepatitis in individuals from Korea.