<i>GPX3</i> Variant Genotype Affects the Risk of Developing Severe Forms of COVID-19

In SARS-CoV-2 infection, excessive activation of the immune system intensively increases reactive oxygen species levels, causing harmful hyperinflammatory and oxidative state cumulative effects which may contribute to COVID-19 severity. Therefore, we assumed that antioxidant genetic profile, indepen...

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Main Authors: Marko Markovic, Jovan Ranin, Zoran Bukumiric, Djurdja Jerotic, Ana Savic-Radojevic, Marija Pljesa-Ercegovac, Tatjana Djukic, Marko Ercegovac, Milika Asanin, Ivana Milosevic, Goran Stevanovic, Tatjana Simic, Vesna Coric, Marija Matic
Format: Article
Language:English
Published: MDPI AG 2023-11-01
Series:International Journal of Molecular Sciences
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Online Access:https://www.mdpi.com/1422-0067/24/22/16151
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author Marko Markovic
Jovan Ranin
Zoran Bukumiric
Djurdja Jerotic
Ana Savic-Radojevic
Marija Pljesa-Ercegovac
Tatjana Djukic
Marko Ercegovac
Milika Asanin
Ivana Milosevic
Goran Stevanovic
Tatjana Simic
Vesna Coric
Marija Matic
author_facet Marko Markovic
Jovan Ranin
Zoran Bukumiric
Djurdja Jerotic
Ana Savic-Radojevic
Marija Pljesa-Ercegovac
Tatjana Djukic
Marko Ercegovac
Milika Asanin
Ivana Milosevic
Goran Stevanovic
Tatjana Simic
Vesna Coric
Marija Matic
author_sort Marko Markovic
collection DOAJ
description In SARS-CoV-2 infection, excessive activation of the immune system intensively increases reactive oxygen species levels, causing harmful hyperinflammatory and oxidative state cumulative effects which may contribute to COVID-19 severity. Therefore, we assumed that antioxidant genetic profile, independently and complemented with laboratory markers, modulates COVID-19 severity. The study included 265 COVID-19 patients. Polymorphism of G<i>STM1</i>, <i>GSTT1</i>, <i>Nrf2 rs6721961</i>, <i>GSTM3 rs1332018</i>, <i>GPX3 rs8177412, GSTP1 rs1695</i>, <i>GSTO1 rs4925</i>, <i>GSTO2 rs156697</i>, <i>SOD2 rs4880</i> and <i>GPX1 rs1050450</i> genes was determined with appropriate PCR-based methods. Inflammation (interleukin-6, CRP, fibrinogen, ferritin) and organ damage (urea, creatinine, transaminases and LDH) markers, complete blood count and coagulation status (d-dimer, fibrinogen) were measured. We found significant association for COVID-19 progression for patients with lymphocytes below 1.0 × 10<sup>9</sup>/L (OR = 2.97, <i>p</i> = 0.002). Increased IL-6 and CRP were also associated with disease progression (OR = 8.52, <i>p</i> = 0.001, and OR = 10.97, <i>p</i> < 0.001, respectively), as well as elevated plasma AST and LDH (OR = 2.25, <i>p</i> = 0.021, and OR = 4.76, <i>p</i> < 0.001, respectively). Of all the examined polymorphisms, we found significant association with the risk of developing severe forms of COVID-19 for <i>GPX3 rs8177412</i> variant genotype (OR = 2.42, <i>p</i> = 0.032). This finding could be of particular importance in the future, complementing other diagnostic tools for prediction of COVID-19 disease course.
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spelling doaj.art-ea86bcace08b4d0dbc81d4ad5a15ac9a2023-11-24T14:46:12ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-11-0124221615110.3390/ijms242216151<i>GPX3</i> Variant Genotype Affects the Risk of Developing Severe Forms of COVID-19Marko Markovic0Jovan Ranin1Zoran Bukumiric2Djurdja Jerotic3Ana Savic-Radojevic4Marija Pljesa-Ercegovac5Tatjana Djukic6Marko Ercegovac7Milika Asanin8Ivana Milosevic9Goran Stevanovic10Tatjana Simic11Vesna Coric12Marija Matic13Clinic of Infectious and Tropical Diseases, University Clinical Centre of Serbia, 11000 Belgrade, SerbiaClinic of Infectious and Tropical Diseases, University Clinical Centre of Serbia, 11000 Belgrade, SerbiaFaculty of Medicine, University of Belgrade, 11000 Belgrade, SerbiaFaculty of Medicine, University of Belgrade, 11000 Belgrade, SerbiaFaculty of Medicine, University of Belgrade, 11000 Belgrade, SerbiaFaculty of Medicine, University of Belgrade, 11000 Belgrade, SerbiaFaculty of Medicine, University of Belgrade, 11000 Belgrade, SerbiaFaculty of Medicine, University of Belgrade, 11000 Belgrade, SerbiaFaculty of Medicine, University of Belgrade, 11000 Belgrade, SerbiaClinic of Infectious and Tropical Diseases, University Clinical Centre of Serbia, 11000 Belgrade, SerbiaClinic of Infectious and Tropical Diseases, University Clinical Centre of Serbia, 11000 Belgrade, SerbiaFaculty of Medicine, University of Belgrade, 11000 Belgrade, SerbiaFaculty of Medicine, University of Belgrade, 11000 Belgrade, SerbiaFaculty of Medicine, University of Belgrade, 11000 Belgrade, SerbiaIn SARS-CoV-2 infection, excessive activation of the immune system intensively increases reactive oxygen species levels, causing harmful hyperinflammatory and oxidative state cumulative effects which may contribute to COVID-19 severity. Therefore, we assumed that antioxidant genetic profile, independently and complemented with laboratory markers, modulates COVID-19 severity. The study included 265 COVID-19 patients. Polymorphism of G<i>STM1</i>, <i>GSTT1</i>, <i>Nrf2 rs6721961</i>, <i>GSTM3 rs1332018</i>, <i>GPX3 rs8177412, GSTP1 rs1695</i>, <i>GSTO1 rs4925</i>, <i>GSTO2 rs156697</i>, <i>SOD2 rs4880</i> and <i>GPX1 rs1050450</i> genes was determined with appropriate PCR-based methods. Inflammation (interleukin-6, CRP, fibrinogen, ferritin) and organ damage (urea, creatinine, transaminases and LDH) markers, complete blood count and coagulation status (d-dimer, fibrinogen) were measured. We found significant association for COVID-19 progression for patients with lymphocytes below 1.0 × 10<sup>9</sup>/L (OR = 2.97, <i>p</i> = 0.002). Increased IL-6 and CRP were also associated with disease progression (OR = 8.52, <i>p</i> = 0.001, and OR = 10.97, <i>p</i> < 0.001, respectively), as well as elevated plasma AST and LDH (OR = 2.25, <i>p</i> = 0.021, and OR = 4.76, <i>p</i> < 0.001, respectively). Of all the examined polymorphisms, we found significant association with the risk of developing severe forms of COVID-19 for <i>GPX3 rs8177412</i> variant genotype (OR = 2.42, <i>p</i> = 0.032). This finding could be of particular importance in the future, complementing other diagnostic tools for prediction of COVID-19 disease course.https://www.mdpi.com/1422-0067/24/22/16151oxidative stressCOVID-19disease progressionantioxidant genetic profileGPX3inflammatory markers
spellingShingle Marko Markovic
Jovan Ranin
Zoran Bukumiric
Djurdja Jerotic
Ana Savic-Radojevic
Marija Pljesa-Ercegovac
Tatjana Djukic
Marko Ercegovac
Milika Asanin
Ivana Milosevic
Goran Stevanovic
Tatjana Simic
Vesna Coric
Marija Matic
<i>GPX3</i> Variant Genotype Affects the Risk of Developing Severe Forms of COVID-19
International Journal of Molecular Sciences
oxidative stress
COVID-19
disease progression
antioxidant genetic profile
GPX3
inflammatory markers
title <i>GPX3</i> Variant Genotype Affects the Risk of Developing Severe Forms of COVID-19
title_full <i>GPX3</i> Variant Genotype Affects the Risk of Developing Severe Forms of COVID-19
title_fullStr <i>GPX3</i> Variant Genotype Affects the Risk of Developing Severe Forms of COVID-19
title_full_unstemmed <i>GPX3</i> Variant Genotype Affects the Risk of Developing Severe Forms of COVID-19
title_short <i>GPX3</i> Variant Genotype Affects the Risk of Developing Severe Forms of COVID-19
title_sort i gpx3 i variant genotype affects the risk of developing severe forms of covid 19
topic oxidative stress
COVID-19
disease progression
antioxidant genetic profile
GPX3
inflammatory markers
url https://www.mdpi.com/1422-0067/24/22/16151
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