Association of GSTM1 and GSTT1 gene polymorphisms with COVID-19 susceptibility and its outcome

J Med Virol. 2021 Sep;93(9):5446-5451. doi: 10.1002/jmv.27076. Epub 2021 Jun 12.

Abstract

Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has become a global health issue and develops into a broad range of illnesses from asymptomatic to fatal respiratory diseases. SARS-CoV-2 infection is associated with oxidative stress that triggers cytokine production, inflammation, and other pathophysiological processes. Glutathione-S-transferase (GST) is an important enzyme that catalyzes the conjugation of glutathione (GSH) with electrophiles to protect the cell from oxidative damage and participates in the antioxidant defense mechanism in the lungs. Thus, in this study, we investigated the role of GSTM1 and GSTT1 gene polymorphism with COVID-19 susceptibility, as well as its outcome. The study included 269 RT-PCR confirmed COVID-19 patients with mild (n = 149) and severe (n = 120) conditions. All subjects were genotyped for GSTM1 and GSTT1 by multiplex polymerase chain reaction (mPCR) followed by statistical analysis. The frequency of GSTM1-/- , GSTT1-/- and GSTM1-/- /GSTT1-/- was higher in severe COVID-19 patients as compared to mild patients but we did not observe a significant association. In the Cox hazard model, death was significantly 2.28-fold higher in patients with the GSTT1-/- genotype (p = 0.047). In combination, patients having GSTM1+/+ and GSTT1-/- genotypes showed a poor survival rate (p = 0.02). Our results suggested that COVID-19 patients with the GSTT1-/- genotype showed higher mortality.

Keywords: COVID-19; GSTM1; GSTT1; Oxidative Stress; SARS-CoV-2; mPCR.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Alleles
  • COVID-19 / genetics*
  • COVID-19 / mortality
  • COVID-19 / pathology
  • COVID-19 / virology
  • COVID-19 Nucleic Acid Testing
  • Female
  • Follow-Up Studies
  • Gene Expression
  • Gene Frequency
  • Genetic Predisposition to Disease*
  • Glutathione / metabolism
  • Glutathione Transferase / genetics*
  • Humans
  • Male
  • Middle Aged
  • Oxidative Stress
  • Polymorphism, Genetic*
  • Proportional Hazards Models
  • SARS-CoV-2 / pathogenicity*
  • Severity of Illness Index

Substances

  • glutathione S-transferase T1
  • Glutathione Transferase
  • glutathione S-transferase M1
  • Glutathione