Heme oxygenase-1 and hemopexin gene polymorphisms and the risk of anti-tuberculosis drug-induced hepatotoxicity in China

Pharmacogenomics. 2022 May;23(7):431-441. doi: 10.2217/pgs-2022-0015. Epub 2022 Apr 26.

Abstract

Objective: To assess whether the risk of anti-tuberculosis drug-induced hepatotoxicity (ATDH) might be influenced by heme oxygenase-1 (HMOX1) and hemopexin (HPX) gene polymorphisms. Methods: A dynamic anti-tuberculosis treatment cohort was constructed, and the 1:4 matched nested case-control study was analysed. Eight single-nucleotide polymorphisms (SNPs) of the two genes were selected for genotyping and Bonferroni correction was performed to correct for multiple comparison. Results: Overall, 7.8% of patients developed ATDH. SNP rs1807714 in the HMOX1 gene had decreased effects on the risk of moderate and severe hepatotoxicity under the dominant and additive models, and hepatocellular injury under the additive model. SNP rs2682099 in the HPX gene had increased effects on the risk of moderate and severe hepatotoxicity under the recessive model. However, these associations disappeared after Bonferroni correction. Conclusion:HMOX1 and HPX gene polymorphisms might not be associated with susceptibility to ATDH in the Chinese population.

Keywords: anti-tuberculosis drug-induced hepatotoxicity; genetic polymorphism; heme oxygenase 1; hemopexin; nested case–control study.

MeSH terms

  • Antitubercular Agents* / adverse effects
  • Case-Control Studies
  • Chemical and Drug Induced Liver Injury* / genetics
  • Genetic Predisposition to Disease
  • Genotype
  • Heme Oxygenase-1 / genetics*
  • Hemopexin / genetics
  • Humans
  • Polymorphism, Single Nucleotide / genetics

Substances

  • Antitubercular Agents
  • Hemopexin
  • HMOX1 protein, human
  • Heme Oxygenase-1