Superoxide Dismutase Gene (SOD 1, SOD2, and SOD3) Polymorphisms and Antituberculosis Drug-induced Hepatitis

Abstract

Purpose: Drug-induced liver injury (DILI) is a serious issue often leading to discontinuation of the proper regimen of antituberculosis drugs (AID). 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 AID-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 AID-induced hepatitis. The frequency of genotypes carrying minor Results (GA or GO) 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 AID-induced hepatitis and ATD-tolerant controls. Conclusions: These findings suggest that rs2070424 of SOD1 is significantly associated with AID-induced hepatitis. This genetic variant may be a risk factor for AID-induced hepatitis in individuals from Korea.