GSTP1 and GSTM3 Variant Alleles Affect Susceptibility and Severity of COVID-19

Vesna Coric; Ivana Milosevic; Tatjana Djukic; Zoran Bukumiric; Ana Savic-Radojevic; Marija Matic; Djurdja Jerotic; Nevena Todorovic; Milika Asanin; Marko Ercegovac; Jovan Ranin; Goran Stevanovic; Marija Pljesa-Ercegovac; Tatjana Simic

doi:10.3389/fmolb.2021.747493

GSTP1 and GSTM3 Variant Alleles Affect Susceptibility and Severity of COVID-19

Front Mol Biosci. 2021 Dec 20:8:747493. doi: 10.3389/fmolb.2021.747493. eCollection 2021.

Authors

Vesna Coric^{1

2}, Ivana Milosevic^{1

3}, Tatjana Djukic^{1

2}, Zoran Bukumiric^{1

4}, Ana Savic-Radojevic^{1

2}, Marija Matic^{1

2}, Djurdja Jerotic^{1

2}, Nevena Todorovic³, Milika Asanin^{1

5}, Marko Ercegovac^{1

6}, Jovan Ranin^{1

3}, Goran Stevanovic^{1

3}, Marija Pljesa-Ercegovac^{1

2}, Tatjana Simic^{1

2

7}

Affiliations

¹ Faculty of Medicine, University of Belgrade, Belgrade, Serbia.
² Institute of Medical and Clinical Biochemistry, Belgrade, Serbia.
³ Clinic of Infectious and Tropical Diseases, Clinical Centre of Serbia, Belgrade, Serbia.
⁴ Institute of Medical Statistics and Informatics, Belgrade, Serbia.
⁵ Clinic of Neurology, Clinical Centre of Serbia, Belgrade, Serbia.
⁶ Clinic of Cardiology, Clinical Centre of Serbia, Belgrade, Serbia.
⁷ Serbian Academy of Sciences and Arts, Belgrade, Serbia.

Abstract

Based on the premise that oxidative stress plays an important role in severe acute respiratory syndrome coronavirus (SARS-CoV-2) infection, we speculated that variations in the antioxidant activities of different members of the glutathione S-transferase family of enzymes might modulate individual susceptibility towards development of clinical manifestations in COVID-19. The distribution of polymorphisms in cytosolic glutathione S-transferases GSTA1, GSTM1, GSTM3, GSTP1 (rs1695 and rs1138272), and GSTT1 were assessed in 207 COVID-19 patients and 252 matched healthy individuals, emphasizing their individual and cumulative effect in disease development and severity. GST polymorphisms were determined by appropriate PCR methods. Among six GST polymorphisms analyzed in this study, GSTP1 rs1695 and GSTM3 were found to be associated with COVID-19. Indeed, the data obtained showed that individuals carrying variant GSTP1-Val allele exhibit lower odds of COVID-19 development (p = 0.002), contrary to carriers of variant GSTM3-CC genotype which have higher odds for COVID-19 (p = 0.024). Moreover, combined GSTP1 (rs1138272 and rs1695) and GSTM3 genotype exhibited cumulative risk regarding both COVID-19 occurrence and COVID-19 severity (p = 0.001 and p = 0.025, respectively). Further studies are needed to clarify the exact roles of specific glutathione S-transferases once the SARS-CoV-2 infection is initiated in the host cell.

Keywords: COVID-19; GSTM3; GSTP1; glutathione transferases; oxidative stress; polymorphisms.