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

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

JOURNAL=Frontiers in Molecular Biosciences

VOLUME=8

YEAR=2021

URL=https://www.frontiersin.org/journals/molecular-biosciences/articles/10.3389/fmolb.2021.747493

DOI=10.3389/fmolb.2021.747493

ISSN=2296-889X

ABSTRACT=<p>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 <italic>GSTA1</italic>, <italic>GSTM1</italic>, <italic>GSTM3</italic>, <italic>GSTP1</italic> (<italic>rs1695</italic> and <italic>rs1138272</italic>), and <italic>GSTT1</italic> were assessed in 207 COVID-19 patients and 252 matched healthy individuals, emphasizing their individual and cumulative effect in disease development and severity. <italic>GST</italic> polymorphisms were determined by appropriate PCR methods. Among six <italic>GST</italic> polymorphisms analyzed in this study, <italic>GSTP1</italic> rs1695 and <italic>GSTM3</italic> were found to be associated with COVID-19. Indeed, the data obtained showed that individuals carrying variant <italic>GSTP1</italic>-<italic>Val</italic> allele exhibit lower odds of COVID-19 development (<italic>p</italic> = 0.002), contrary to carriers of variant <italic>GSTM3-CC</italic> genotype which have higher odds for COVID-19 (<italic>p</italic> = 0.024). Moreover, combined <italic>GSTP1</italic> (<italic>rs1138272</italic> and <italic>rs1695</italic>) and <italic>GSTM3</italic> genotype exhibited cumulative risk regarding both COVID-19 occurrence and COVID-19 severity (<italic>p</italic> = 0.001 and <italic>p</italic> = 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.</p>