ACE2 and TMPRSS2 genetic polymorphisms as potential predictors of COVID−19 severity and outcome in females

IntroductionACE2 and TMPRSS2 represent the major gateways for SARS-CoV-2 cell entry. The presence of functional ACE2 and TMPRSS2 genetic polymorphisms that affect gene expression may affect the risk of severe form of COVID-19 and its fatal outcome.Material and patientsThis observational study enroll...

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Main Authors: Sanja Matic, Dragan Milovanovic, Zeljko Mijailovic, Predrag Djurdjevic, Srdjan Stefanovic, Danijela Todorovic, Katarina Vitosevic, Vanja Canovic, Suzana Popovic, Nevena Milivojevic Dimitrijevic, Marko Zivanovic, Dragana Seklic, Sanja Aleksic, Nemanja Djordjevic, Milena Vukic, Nenad Vukovic, Nenad Filipovic, Dejan Baskic, Natasa Djordjevic
Format: Article
Language:English
Published: Frontiers Media S.A. 2024-12-01
Series:Frontiers in Medicine
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Online Access:https://www.frontiersin.org/articles/10.3389/fmed.2024.1493815/full
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author Sanja Matic
Dragan Milovanovic
Dragan Milovanovic
Zeljko Mijailovic
Zeljko Mijailovic
Predrag Djurdjevic
Predrag Djurdjevic
Srdjan Stefanovic
Danijela Todorovic
Katarina Vitosevic
Katarina Vitosevic
Vanja Canovic
Suzana Popovic
Nevena Milivojevic Dimitrijevic
Nevena Milivojevic Dimitrijevic
Marko Zivanovic
Marko Zivanovic
Dragana Seklic
Sanja Aleksic
Nemanja Djordjevic
Nemanja Djordjevic
Milena Vukic
Nenad Vukovic
Nenad Filipovic
Nenad Filipovic
Dejan Baskic
Dejan Baskic
Natasa Djordjevic
author_facet Sanja Matic
Dragan Milovanovic
Dragan Milovanovic
Zeljko Mijailovic
Zeljko Mijailovic
Predrag Djurdjevic
Predrag Djurdjevic
Srdjan Stefanovic
Danijela Todorovic
Katarina Vitosevic
Katarina Vitosevic
Vanja Canovic
Suzana Popovic
Nevena Milivojevic Dimitrijevic
Nevena Milivojevic Dimitrijevic
Marko Zivanovic
Marko Zivanovic
Dragana Seklic
Sanja Aleksic
Nemanja Djordjevic
Nemanja Djordjevic
Milena Vukic
Nenad Vukovic
Nenad Filipovic
Nenad Filipovic
Dejan Baskic
Dejan Baskic
Natasa Djordjevic
author_sort Sanja Matic
collection DOAJ
description IntroductionACE2 and TMPRSS2 represent the major gateways for SARS-CoV-2 cell entry. The presence of functional ACE2 and TMPRSS2 genetic polymorphisms that affect gene expression may affect the risk of severe form of COVID-19 and its fatal outcome.Material and patientsThis observational study enrolled 178 hospitalized patients diagnosed with SARS-CoV-2 infection at the University Clinical Centre of Kragujevac, Serbia. Demographic, clinical, and laboratory data were gathered at admission. Genotyping for single nucleotide polymorphisms of ACE2 (rs2106809 and rs2074192) and TMPRSS2 (rs2070788 and rs4818239) was performed using the Real-Time PCR method with TaqMan assays.ResultsControlling for other factors of influence, such as CCI, N/L ratio, LDH level, and pO2, we showed that females with TMPRSS2 rs2070788 A/A genotype were less likely to develop severe COVID-19 (odds ratio [OR] [95% confidence interval (95% CI)]: 0.030 [0.001; 0.862]). Additionally, the likelihood of dying of SARS-CoV-2 infection was lower in female carriers of at least one ACE2 rs2106809 C allele (OR [95% CI]: 0.004 [0.000; 0.981]).ConclusionOur findings indicate TMPRSS2 rs2070788 and ACE2 rs2106809 polymorphisms as independent predictors of severity and outcome of COVID-19 in females.
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spelling doaj-art-01120efe32b44368b37596beec8c3ebb2025-08-20T01:57:55ZengFrontiers Media S.A.Frontiers in Medicine2296-858X2024-12-011110.3389/fmed.2024.14938151493815ACE2 and TMPRSS2 genetic polymorphisms as potential predictors of COVID−19 severity and outcome in femalesSanja Matic0Dragan Milovanovic1Dragan Milovanovic2Zeljko Mijailovic3Zeljko Mijailovic4Predrag Djurdjevic5Predrag Djurdjevic6Srdjan Stefanovic7Danijela Todorovic8Katarina Vitosevic9Katarina Vitosevic10Vanja Canovic11Suzana Popovic12Nevena Milivojevic Dimitrijevic13Nevena Milivojevic Dimitrijevic14Marko Zivanovic15Marko Zivanovic16Dragana Seklic17Sanja Aleksic18Nemanja Djordjevic19Nemanja Djordjevic20Milena Vukic21Nenad Vukovic22Nenad Filipovic23Nenad Filipovic24Dejan Baskic25Dejan Baskic26Natasa Djordjevic27Department of Pharmacy, Faculty of Medical Sciences, University of Kragujevac, Kragujevac, SerbiaDepartment of Pharmacology and Toxicology, Faculty of Medical Sciences, University of Kragujevac, Kragujevac, SerbiaDepartment of Clinical Pharmacology, University Clinical Centre Kragujevac, Kragujevac, SerbiaDepartment of Infectious Diseases, Faculty of Medical Sciences, University of Kragujevac, Kragujevac, SerbiaInfectious Diseases Clinic, University Clinical Centre Kragujevac, Kragujevac, SerbiaDepartment of Internal Medicine, Faculty of Medical Sciences, University of Kragujevac, Kragujevac, SerbiaClinic for Haematology, University Clinical Centre Kragujevac, Kragujevac, SerbiaDepartment of Pharmacy, Faculty of Medical Sciences, University of Kragujevac, Kragujevac, SerbiaDepartment of Genetics, Faculty of Medical Sciences, University of Kragujevac, Kragujevac, SerbiaDepartment of Forensic Medicine, Faculty of Medical Sciences, University of Kragujevac, Kragujevac, Serbia0Department of Forensic Medicine and Toxicology, University Clinical Center Kragujevac, Kragujevac, Serbia0Department of Forensic Medicine and Toxicology, University Clinical Center Kragujevac, Kragujevac, Serbia1Centre for Molecular Medicine and Stem Cell Research, Faculty of Medical Sciences, University of Kragujevac, Kragujevac, Serbia2Bioengineering Research and Development Center (BioIRC), Kragujevac, Serbia3Department of Sciences Institute for Information Technologies Kragujevac, University of Kragujevac, Kragujevac, Serbia2Bioengineering Research and Development Center (BioIRC), Kragujevac, Serbia3Department of Sciences Institute for Information Technologies Kragujevac, University of Kragujevac, Kragujevac, Serbia3Department of Sciences Institute for Information Technologies Kragujevac, University of Kragujevac, Kragujevac, SerbiaClinic for Haematology, University Clinical Centre Kragujevac, Kragujevac, SerbiaDepartment of Infectious Diseases, Faculty of Medical Sciences, University of Kragujevac, Kragujevac, SerbiaInfectious Diseases Clinic, University Clinical Centre Kragujevac, Kragujevac, Serbia4Department of Chemistry, Faculty of Sciences, University of Kragujevac, Kragujevac, Serbia4Department of Chemistry, Faculty of Sciences, University of Kragujevac, Kragujevac, Serbia2Bioengineering Research and Development Center (BioIRC), Kragujevac, Serbia5Faculty of Engineering, University of Kragujevac, Kragujevac, Serbia1Centre for Molecular Medicine and Stem Cell Research, Faculty of Medical Sciences, University of Kragujevac, Kragujevac, Serbia6Institute of Public Health Kragujevac, Kragujevac, SerbiaDepartment of Pharmacology and Toxicology, Faculty of Medical Sciences, University of Kragujevac, Kragujevac, SerbiaIntroductionACE2 and TMPRSS2 represent the major gateways for SARS-CoV-2 cell entry. The presence of functional ACE2 and TMPRSS2 genetic polymorphisms that affect gene expression may affect the risk of severe form of COVID-19 and its fatal outcome.Material and patientsThis observational study enrolled 178 hospitalized patients diagnosed with SARS-CoV-2 infection at the University Clinical Centre of Kragujevac, Serbia. Demographic, clinical, and laboratory data were gathered at admission. Genotyping for single nucleotide polymorphisms of ACE2 (rs2106809 and rs2074192) and TMPRSS2 (rs2070788 and rs4818239) was performed using the Real-Time PCR method with TaqMan assays.ResultsControlling for other factors of influence, such as CCI, N/L ratio, LDH level, and pO2, we showed that females with TMPRSS2 rs2070788 A/A genotype were less likely to develop severe COVID-19 (odds ratio [OR] [95% confidence interval (95% CI)]: 0.030 [0.001; 0.862]). Additionally, the likelihood of dying of SARS-CoV-2 infection was lower in female carriers of at least one ACE2 rs2106809 C allele (OR [95% CI]: 0.004 [0.000; 0.981]).ConclusionOur findings indicate TMPRSS2 rs2070788 and ACE2 rs2106809 polymorphisms as independent predictors of severity and outcome of COVID-19 in females.https://www.frontiersin.org/articles/10.3389/fmed.2024.1493815/fullACE2TMPRSS2COVID-19severityoutcome
spellingShingle Sanja Matic
Dragan Milovanovic
Dragan Milovanovic
Zeljko Mijailovic
Zeljko Mijailovic
Predrag Djurdjevic
Predrag Djurdjevic
Srdjan Stefanovic
Danijela Todorovic
Katarina Vitosevic
Katarina Vitosevic
Vanja Canovic
Suzana Popovic
Nevena Milivojevic Dimitrijevic
Nevena Milivojevic Dimitrijevic
Marko Zivanovic
Marko Zivanovic
Dragana Seklic
Sanja Aleksic
Nemanja Djordjevic
Nemanja Djordjevic
Milena Vukic
Nenad Vukovic
Nenad Filipovic
Nenad Filipovic
Dejan Baskic
Dejan Baskic
Natasa Djordjevic
ACE2 and TMPRSS2 genetic polymorphisms as potential predictors of COVID−19 severity and outcome in females
Frontiers in Medicine
ACE2
TMPRSS2
COVID-19
severity
outcome
title ACE2 and TMPRSS2 genetic polymorphisms as potential predictors of COVID−19 severity and outcome in females
title_full ACE2 and TMPRSS2 genetic polymorphisms as potential predictors of COVID−19 severity and outcome in females
title_fullStr ACE2 and TMPRSS2 genetic polymorphisms as potential predictors of COVID−19 severity and outcome in females
title_full_unstemmed ACE2 and TMPRSS2 genetic polymorphisms as potential predictors of COVID−19 severity and outcome in females
title_short ACE2 and TMPRSS2 genetic polymorphisms as potential predictors of COVID−19 severity and outcome in females
title_sort ace2 and tmprss2 genetic polymorphisms as potential predictors of covid 19 severity and outcome in females
topic ACE2
TMPRSS2
COVID-19
severity
outcome
url https://www.frontiersin.org/articles/10.3389/fmed.2024.1493815/full
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