Increased Risk of Antituberculosis Drugs-Induced Maculopapular Eruption in Patients with Superoxide Dismutase 1 Gene Mutation

Abstract

Rationale Of various adverse reactions to antituberculosis drugs (ATD), maculopapular eruption (MPE) is the most common cause leading to discontinuation of the medication. The pathogenesis of ATD-induced MPE is poorly understood, but oxidative stress induced by the ATD metabolites might play a role in the development of MPE. This study aimed to examine the associations between genetic polymorphisms in superoxide dismutase genes (SOD1, SOD2 and SOD3) and ATD-induced MPE.

Methods From the patients receiving the first line ATD including isoniazid, rifampicin, ethambutol and pyrazinamide, 75 patients with ATD-induced MPE and 237 ATD-tolerant control were included in this study. Four single nucleotide polymorphisms (SNP) in SOD1 (rs2070424), SOD2 (rs4880) and SOD3 (rs2536512 and rs1799895) were selected based on the previously reported roles in the literature and genotypes in the study subjects. Genotype-phenotype association was examined by logistic regression analysis adjusting for gender and age.

Results In rs2070424 (Ivs3-251A/G) of SOD1, the frequency of genotype carrying the minor allele (GA + GG) was higher in patients with ATD-induced MPE compared with ATD-tolerant controls (P = 0.018, OR = 2.42, 95% CI 1.16-5.05). The other polymorphisms in SOD2 and SOD3 did not show significant difference of genotypes between case and control group.

Conclusions Intron SNP rs2070424 of SOD1 (Ivs3-251A/G) showed significant association with ATD-induced MPE. These findings suggest that this SOD1 genetic variant may increase the risk of ATD-induced MPE.