P1245 Polymorphic Variants of HSD3B1 Gene Confer Different Outcome in Specific Subgroups of Patients Infected With SARS-CoV-2
Introduction: Severe respiratory syndrome coronavirus 2 (SARS-CoV-2) uses the androgen receptor (AR), through ACE2 receptor and TMPRSS2, to enter nasal and upper airways epithelial cells. Genetic analyses revealed that HSD3B1 P1245C polymorphic variant increases dihydrotestosterone production and up...
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Frontiers Media S.A.
2022-07-01
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fmed.2021.793728/full |
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| author | Samantha Epistolio Giulia Ramelli Margaret Ottaviano Emanuele Crupi Laura Marandino Maira Biggiogero Pier Andrea Maida Pier Andrea Maida Lorenzo Ruinelli Ursula Vogl Dylan Mangan Mariarosa Pascale Marco Cantù Alessandro Ceschi Alessandro Ceschi Alessandro Ceschi Alessandro Ceschi Enos Bernasconi Enos Bernasconi Luca Mazzucchelli Luca Mazzucchelli Carlo Catapano Carlo Catapano Andrea Alimonti Andrea Alimonti Christian Garzoni Silke Gillessen Sommer Silke Gillessen Sommer Federico Mattia Stefanini Alessandra Franzetti-Pellanda Milo Frattini Ricardo Pereira Mestre Ricardo Pereira Mestre |
| author_facet | Samantha Epistolio Giulia Ramelli Margaret Ottaviano Emanuele Crupi Laura Marandino Maira Biggiogero Pier Andrea Maida Pier Andrea Maida Lorenzo Ruinelli Ursula Vogl Dylan Mangan Mariarosa Pascale Marco Cantù Alessandro Ceschi Alessandro Ceschi Alessandro Ceschi Alessandro Ceschi Enos Bernasconi Enos Bernasconi Luca Mazzucchelli Luca Mazzucchelli Carlo Catapano Carlo Catapano Andrea Alimonti Andrea Alimonti Christian Garzoni Silke Gillessen Sommer Silke Gillessen Sommer Federico Mattia Stefanini Alessandra Franzetti-Pellanda Milo Frattini Ricardo Pereira Mestre Ricardo Pereira Mestre |
| author_sort | Samantha Epistolio |
| collection | DOAJ |
| description | Introduction: Severe respiratory syndrome coronavirus 2 (SARS-CoV-2) uses the androgen receptor (AR), through ACE2 receptor and TMPRSS2, to enter nasal and upper airways epithelial cells. Genetic analyses revealed that HSD3B1 P1245C polymorphic variant increases dihydrotestosterone production and upregulation of TMPRSS2 with respect to P1245A variant, thus possibly influencing SARS-CoV-2 infection. Our aim was to characterize the HSD3B1 polymorphism status and its potential association with clinical outcomes in hospitalized patients with COVID-19 in Southern Switzerland.Materials and Methods: The cohort included 400 patients hospitalized for COVID-19 during the first wave between February and May 2020 in two different hospitals of Canton Ticino. Genomic DNA was extracted from formalin-fixed paraffin-embedded tissue blocks, and HSD3B1 gene polymorphism was evaluated by Sanger sequencing. Statistical associations were verified using different test.Results:HSD3B1 polymorphic variants were not associated with a single classical factor related to worse clinical prognosis in hospitalized patients with SARS-CoV-2. However, in specific subgroups, HSD3B1 variants played a clinical role: intensive care unit admission was more probable in patients with P1245C diabetes compared with P1245A individuals without this comorbidity and death was more associated with hypertensive P1245A>C cases than patients with P1245A diabetes without hypertension.Discussion: This is the first study showing that HSD3B1 gene status may influence the severity of SARS-CoV-2 infection. If confirmed, our results could lead to the introduction of HSD3B1 gene status analysis in patients infected with SARS-CoV-2 to predict clinical outcome. |
| first_indexed | 2024-04-13T14:39:02Z |
| format | Article |
| id | doaj.art-8114a4190eec424eadb0197bced4cfb4 |
| institution | Directory Open Access Journal |
| issn | 2296-858X |
| language | English |
| last_indexed | 2024-04-13T14:39:02Z |
| publishDate | 2022-07-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Medicine |
| spelling | doaj.art-8114a4190eec424eadb0197bced4cfb42022-12-22T02:42:57ZengFrontiers Media S.A.Frontiers in Medicine2296-858X2022-07-01810.3389/fmed.2021.793728793728P1245 Polymorphic Variants of HSD3B1 Gene Confer Different Outcome in Specific Subgroups of Patients Infected With SARS-CoV-2Samantha Epistolio0Giulia Ramelli1Margaret Ottaviano2Emanuele Crupi3Laura Marandino4Maira Biggiogero5Pier Andrea Maida6Pier Andrea Maida7Lorenzo Ruinelli8Ursula Vogl9Dylan Mangan10Mariarosa Pascale11Marco Cantù12Alessandro Ceschi13Alessandro Ceschi14Alessandro Ceschi15Alessandro Ceschi16Enos Bernasconi17Enos Bernasconi18Luca Mazzucchelli19Luca Mazzucchelli20Carlo Catapano21Carlo Catapano22Andrea Alimonti23Andrea Alimonti24Christian Garzoni25Silke Gillessen Sommer26Silke Gillessen Sommer27Federico Mattia Stefanini28Alessandra Franzetti-Pellanda29Milo Frattini30Ricardo Pereira Mestre31Ricardo Pereira Mestre32Laboratory of Molecular Pathology, Institute of Pathology, Ente Ospedaliero Cantonale, Locarno, SwitzerlandLaboratory of Molecular Pathology, Institute of Pathology, Ente Ospedaliero Cantonale, Locarno, SwitzerlandOncology Institute of Southern Switzerland, Ente Ospedaliero Cantonale, Bellinzona, SwitzerlandOncology Institute of Southern Switzerland, Ente Ospedaliero Cantonale, Bellinzona, SwitzerlandOncology Institute of Southern Switzerland, Ente Ospedaliero Cantonale, Bellinzona, SwitzerlandClinic Research Unit, Clinica Luganese Moncucco, Lugano, SwitzerlandClinic Research Unit, Clinica Luganese Moncucco, Lugano, SwitzerlandClinic of Internal Medicine and Infectious Diseases, Clinica Luganese Moncucco, Lugano, SwitzerlandInformatics and Communication Technology, Ente Ospedaliero Cantonale, Bellinzona, SwitzerlandOncology Institute of Southern Switzerland, Ente Ospedaliero Cantonale, Bellinzona, SwitzerlandOncology Institute of Southern Switzerland, Ente Ospedaliero Cantonale, Bellinzona, SwitzerlandClinical Trial Unit, Ente Ospedaliero Cantonale, Lugano, SwitzerlandInstitute of Laboratory Medicine, Ente Ospedaliero Cantonale, Lugano, SwitzerlandClinical Trial Unit, Ente Ospedaliero Cantonale, Lugano, SwitzerlandDivision of Clinical Pharmacology and Toxicology, Institute of Pharmacological Sciences of Southern Switzerland, Ente Ospedaliero Cantonale, Lugano, SwitzerlandFaculty of Biomedical Sciences, Università della Svizzera italiana, Lugano, Switzerland0Department of Clinical Pharmacology and Toxicology, University Hospital Zürich, Zürich, Switzerland1Division of Infectious Diseases, Department of Medicine, Ente Ospedaliero Cantonale, Università della Svizzera italiana, Lugano, Switzerland2Faculty of Medicine, Division of Biomedical Sciences, University of Geneva, Geneva, SwitzerlandLaboratory of Molecular Pathology, Institute of Pathology, Ente Ospedaliero Cantonale, Locarno, SwitzerlandFaculty of Biomedical Sciences, Università della Svizzera italiana, Lugano, SwitzerlandFaculty of Biomedical Sciences, Università della Svizzera italiana, Lugano, Switzerland3Faculty of Experimental Therapeutics, Institute of Oncology Research, Università della Svizzera italiana, Bellinzona, SwitzerlandFaculty of Biomedical Sciences, Università della Svizzera italiana, Lugano, Switzerland4Department of Molecular Oncology, Institute of Oncology Research, Università della Svizzera italiana, Bellinzona, SwitzerlandClinic of Internal Medicine and Infectious Diseases, Clinica Luganese Moncucco, Lugano, SwitzerlandOncology Institute of Southern Switzerland, Ente Ospedaliero Cantonale, Bellinzona, SwitzerlandFaculty of Biomedical Sciences, Università della Svizzera italiana, Lugano, Switzerland5Department of Enviromental Science and Policy, Faculty of Science and Technology-ESP, University of Milan, Milan, ItalyClinic Research Unit, Clinica Luganese Moncucco, Lugano, SwitzerlandLaboratory of Molecular Pathology, Institute of Pathology, Ente Ospedaliero Cantonale, Locarno, SwitzerlandOncology Institute of Southern Switzerland, Ente Ospedaliero Cantonale, Bellinzona, Switzerland3Faculty of Experimental Therapeutics, Institute of Oncology Research, Università della Svizzera italiana, Bellinzona, SwitzerlandIntroduction: Severe respiratory syndrome coronavirus 2 (SARS-CoV-2) uses the androgen receptor (AR), through ACE2 receptor and TMPRSS2, to enter nasal and upper airways epithelial cells. Genetic analyses revealed that HSD3B1 P1245C polymorphic variant increases dihydrotestosterone production and upregulation of TMPRSS2 with respect to P1245A variant, thus possibly influencing SARS-CoV-2 infection. Our aim was to characterize the HSD3B1 polymorphism status and its potential association with clinical outcomes in hospitalized patients with COVID-19 in Southern Switzerland.Materials and Methods: The cohort included 400 patients hospitalized for COVID-19 during the first wave between February and May 2020 in two different hospitals of Canton Ticino. Genomic DNA was extracted from formalin-fixed paraffin-embedded tissue blocks, and HSD3B1 gene polymorphism was evaluated by Sanger sequencing. Statistical associations were verified using different test.Results:HSD3B1 polymorphic variants were not associated with a single classical factor related to worse clinical prognosis in hospitalized patients with SARS-CoV-2. However, in specific subgroups, HSD3B1 variants played a clinical role: intensive care unit admission was more probable in patients with P1245C diabetes compared with P1245A individuals without this comorbidity and death was more associated with hypertensive P1245A>C cases than patients with P1245A diabetes without hypertension.Discussion: This is the first study showing that HSD3B1 gene status may influence the severity of SARS-CoV-2 infection. If confirmed, our results could lead to the introduction of HSD3B1 gene status analysis in patients infected with SARS-CoV-2 to predict clinical outcome.https://www.frontiersin.org/articles/10.3389/fmed.2021.793728/fullSARS-CoV-2HSD3B1 gene polymorphismandrogen receptordirect sequencingLikelihood-ratio tests |
| spellingShingle | Samantha Epistolio Giulia Ramelli Margaret Ottaviano Emanuele Crupi Laura Marandino Maira Biggiogero Pier Andrea Maida Pier Andrea Maida Lorenzo Ruinelli Ursula Vogl Dylan Mangan Mariarosa Pascale Marco Cantù Alessandro Ceschi Alessandro Ceschi Alessandro Ceschi Alessandro Ceschi Enos Bernasconi Enos Bernasconi Luca Mazzucchelli Luca Mazzucchelli Carlo Catapano Carlo Catapano Andrea Alimonti Andrea Alimonti Christian Garzoni Silke Gillessen Sommer Silke Gillessen Sommer Federico Mattia Stefanini Alessandra Franzetti-Pellanda Milo Frattini Ricardo Pereira Mestre Ricardo Pereira Mestre P1245 Polymorphic Variants of HSD3B1 Gene Confer Different Outcome in Specific Subgroups of Patients Infected With SARS-CoV-2 Frontiers in Medicine SARS-CoV-2 HSD3B1 gene polymorphism androgen receptor direct sequencing Likelihood-ratio tests |
| title | P1245 Polymorphic Variants of HSD3B1 Gene Confer Different Outcome in Specific Subgroups of Patients Infected With SARS-CoV-2 |
| title_full | P1245 Polymorphic Variants of HSD3B1 Gene Confer Different Outcome in Specific Subgroups of Patients Infected With SARS-CoV-2 |
| title_fullStr | P1245 Polymorphic Variants of HSD3B1 Gene Confer Different Outcome in Specific Subgroups of Patients Infected With SARS-CoV-2 |
| title_full_unstemmed | P1245 Polymorphic Variants of HSD3B1 Gene Confer Different Outcome in Specific Subgroups of Patients Infected With SARS-CoV-2 |
| title_short | P1245 Polymorphic Variants of HSD3B1 Gene Confer Different Outcome in Specific Subgroups of Patients Infected With SARS-CoV-2 |
| title_sort | p1245 polymorphic variants of hsd3b1 gene confer different outcome in specific subgroups of patients infected with sars cov 2 |
| topic | SARS-CoV-2 HSD3B1 gene polymorphism androgen receptor direct sequencing Likelihood-ratio tests |
| url | https://www.frontiersin.org/articles/10.3389/fmed.2021.793728/full |
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