ACE2 gene variants may underlie interindividual variability and susceptibility to COVID-19 in the Italian population View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2020-07-17

AUTHORS

Elisa Benetti, Rossella Tita, Ottavia Spiga, Andrea Ciolfi, Giovanni Birolo, Alessandro Bruselles, Gabriella Doddato, Annarita Giliberti, Caterina Marconi, Francesco Musacchia, Tommaso Pippucci, Annalaura Torella, Alfonso Trezza, Floriana Valentino, Margherita Baldassarri, Alfredo Brusco, Rosanna Asselta, Mirella Bruttini, Simone Furini, Marco Seri, Vincenzo Nigro, Giuseppe Matullo, Marco Tartaglia, Francesca Mari, Elisa Frullanti, Chiara Fallerini, Sergio Daga, Susanna Croci, Sara Amitrano, Francesca Fava, Francesca Montagnani, Laura Di Sarno, Andrea Tommasi, Maria Palmieri, Arianna Emiliozzi, Massimiliano Fabbiani, Barbara Rossetti, Giacomo Zanelli, Laura Bergantini, Miriana D’Alessandro, Paolo Cameli, David Bennet, Federico Anedda, Simona Marcantonio, Sabino Scolletta, Federico Franchi, Maria Antonietta Mazzei, Edoardo Conticini, Luca Cantarini, Bruno Frediani, Danilo Tacconi, Marco Feri, Raffaele Scala, Genni Spargi, Marta Corridi, Cesira Nencioni, Gian Piero Caldarelli, Maurizio Spagnesi, Paolo Piacentini, Maria Bandini, Elena Desanctis, Anna Canaccini, Chiara Spertilli, Alice Donati, Luca Guidelli, Leonardo Croci, Agnese Verzuri, Valentina Anemoli, Agostino Ognibene, Massimo Vaghi, Antonella D’Arminio Monforte, Esther Merlini, Mario U. Mondelli, Stefania Mantovani, Serena Ludovisi, Massimo Girardis, Sophie Venturelli, Marco Sita, Andrea Cossarizza, Andrea Antinori, Alessandra Vergori, Stefano Rusconi, Matteo Siano, Arianna Gabrieli, Agostino Riva, Daniela Francisci, Elisabetta Schiaroli, Pier Giorgio Scotton, Francesca Andretta, Sandro Panese, Renzo Scaggiante, Saverio Giuseppe Parisi, Francesco Castelli, Maria Eugenia Quiros-Roldan, Paola Magro, Cristina Minardi, Deborah Castelli, Itala Polesini, Matteo Della Monica, Carmelo Piscopo, Mario Capasso, Roberta Russo, Immacolata Andolfo, Achille Iolascon, Massimo Carella, Marco Castori, Giuseppe Merla, Filippo Aucella, Pamela Raggi, Carmen Marciano, Rita Perna, Matteo Bassetti, Antonio Di Biagio, Maurizio Sanguinetti, Luca Masucci, Chiara Gabbi, Serafina Valente, Susanna Guerrini, Ilaria Meloni, Maria Antonietta Mencarelli, Caterina Lo Rizzo, Elena Bargagli, Marco Mandalà, Alessia Giorli, Lorenzo Salerni, Giuseppe Fiorentino, Patrizia Zucchi, Pierpaolo Parravicini, Elisabetta Menatti, Stefano Baratti, Tullio Trotta, Ferdinando Giannattasio, Gabriella Coiro, Fabio Lena, Domenico A. Coviello, Cristina Mussini, Alessandra Renieri, Anna Maria Pinto

ABSTRACT

In December 2019, an initial cluster of interstitial bilateral pneumonia emerged in Wuhan, China. A human-to-human transmission was assumed and a previously unrecognized entity, termed coronavirus disease-19 (COVID-19) due to a novel coronavirus (SARS-CoV-2) was described. The infection has rapidly spread out all over the world and Italy has been the first European country experiencing the endemic wave with unexpected clinical severity in comparison with Asian countries. It has been shown that SARS-CoV-2 utilizes angiotensin converting enzyme 2 (ACE2) as host receptor and host proteases for cell surface binding and internalization. Thus, a predisposing genetic background can give reason for interindividual disease susceptibility and/or severity. Taking advantage of the Network of Italian Genomes (NIG), here we mined whole-exome sequencing data of 6930 Italian control individuals from five different centers looking for ACE2 variants. A number of variants with a potential impact on protein stability were identified. Among these, three more common missense changes, p.(Asn720Asp), p.(Lys26Arg), and p.(Gly211Arg) were predicted to interfere with protein structure and stabilization. Rare variants likely interfering with the internalization process, namely p.(Leu351Val) and p.(Pro389His), predicted to interfere with SARS-CoV-2 spike protein binding, were also observed. Comparison of ACE2 WES data between a cohort of 131 patients and 258 controls allowed identifying a statistically significant (P value < 0.029) higher allelic variability in controls compared with patients. These findings suggest that a predisposing genetic background may contribute to the observed interindividual clinical variability associated with COVID-19, allowing an evidence-based risk assessment leading to personalized preventive measures and therapeutic options. More... »

PAGES

1602-1614

Journal

TITLE

European Journal of Human Genetics

ISSUE

11

VOLUME

28

Author Affiliations

  • Department of Medical Biotechnologies, University of Siena, Siena, Italy
  • Genetica Medica, Azienda Ospedaliera Universitaria Senese, Siena, Italy
  • Department of Biotechnology, Chemistry and Pharmacy, University of Siena, Siena, Italy
  • Genetics and Rare Diseases Research Division, Ospedale Pediatrico Bambino Gesù, IRCCS, Rome, Italy
  • Department of Medical Sciences, University of Turin, Turin, Italy
  • Department of Oncology and Molecular Medicine, Istituto Superiore di Sanità, Rome, Italy
  • Medical Genetics, University of Siena, Siena, Italy
  • Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy
  • Telethon Institute of Genetics and Medicine, Pozzuoli, Italy
  • Sant’Orsola-Malpighi University Hospital, Bologna, Italy
  • Dipartimento di Medicina di Precisione, Università della Campania “Luigi Vanvitelli”, Napoli, Italy
  • Genetica Medica, Città della Salute e della Scienza, Torino, Italy
  • Humanitas Clinical and Research Center—IRCCS, Rozzano, Milan Italy
  • Genetica Medica, Azienda Ospedaliera Universitaria Senese, Senese, Italy
  • Unit of Respiratory Diseases and Lung Transplantation, Department of Internal and Specialist Medicine, University of Siena, Siena, Italy
  • Dept of Specialized and Internal Medicine, Tropical and Infectious Diseases Unit, Siena, Italy
  • Dept of Emergency and Urgency, Medicine, Surgery and Neurosciences, Unit of Intensive Care Medicine, Siena University Hospital, Siena, Italy
  • Department of Medical, Surgical and Neuro Sciences and Radiological Sciences, Unit of Diagnostic Imaging, University, Siena, Italy
  • Rheumatology Unit, Department of Medicine, Surgery and Neurosciences, University of Siena, Policlinico Le Scotte, Siena, Italy
  • Department of Specialized and Internal Medicine, Infectious Diseases Unit, San Donato Hospital Arezzo, Arezzo, Italy
  • Dept of Emergency, Anesthesia Unit, San Donato Hospital, Arezzo, Italy
  • Department of Specialized and Internal Medicine, Pneumology Unit and UTIP, San Donato Hospital, Arezzo, Italy
  • Department of Emergency, Anesthesia Unit, Misericordia Hospital, Grosseto, Italy
  • Department of Specialized and Internal Medicine, Infectious Diseases Unit, Misericordia Hospital, Grosseto, Italy
  • Clinical Chemical Analysis Laboratory, Misericordia Hospital, Grosseto, Italy
  • Department of Prevention, Azienda USL Toscana Sud Est, Arezzo, Italy
  • Territorial Scientific Technician Department, Azienda USL Toscana Sud Est, Arezzo, Italy
  • Clinical Chemical Analysis Laboratory, San Donato Hospital, Arezzo, Italy
  • Chirurgia Vascolare, Ospedale Maggiore di Crema, Crema, Italy
  • Department of Health Sciences, Clinic of Infectious Diseases, ASST Santi Paolo e Carlo, University of Milan, Milan, Italy
  • Department of Internal Medicine and Therapeutics, University of Pavia, Pavia, Italy
  • Division of Infectious Diseases and Immunology, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy
  • Department of Anesthesia and Intensive Care, University of Modena and Reggio Emilia, Modena, Italy
  • Department of Medical and Surgical Sciences for Children and Adults, University of Modena and Reggio Emilia, Modena, Italy
  • HIV/AIDS Department, National Institute for Infectious Diseases, IRCCS, Lazzaro Spallanzani, Rome, Italy
  • Department of Biomedical and Clinical Sciences Luigi Sacco, University of Milan, Milan, Italy
  • Infectious Diseases Clinic, ‘Santa Maria’ Hospital, University of Perugia, Perugia, Italy
  • Infectious Diseases Clinic, Department of Medicine 2, Azienda Ospedaliera di Perugia and University of Perugia, Santa Maria Hospital, Perugia, Italy
  • Department of Infectious Diseases, Treviso Hospital, Local Health Unit 2 Marca Trevigiana, Treviso, Italy
  • Infectious Diseases Department, Ospedale Civile ‘SS. Giovanni e Paolo’, Venice, Italy
  • Infectious Diseases Clinic, ULSS1 Belluno, Italy
  • Department of Molecular Medicine, University of Padova, Padova, Italy
  • Department of Infectious and Tropical Diseases, University of Brescia and ASST Spedali Civili Hospital, Brescia, Italy
  • Medical Genetics and Laboratory of Medical Genetics Unit, A.O.R.N. ‘Antonio Cardarelli’, Naples, Italy
  • IRCCS SDN, Naples, Italy
  • CEINGE Biotecnologie Avanzate, Naples, Italy
  • Division of Medical Genetics, Fondazione IRCCS Casa Sollievo della Sofferenza Hospital, San Giovanni Rotondo, Italy
  • Department of Medical Sciences, Fondazione IRCCS Casa Sollievo della Sofferenza Hospital, San Giovanni Rotondo, Italy
  • Clinical Trial Office, Fondazione IRCCS Casa Sollievo della Sofferenza Hospital, San Giovanni Rotondo, Italy
  • Infectious Diseases Clinic, Policlinico San Martino Hospital, IRCCS for Cancer Research Genova, Genova, Italy
  • Department of Laboratory Sciences and Infectious Diseases, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy
  • Independent Scientist, Milan, Italy
  • Department of Cardiovascular Diseases, University of Siena, Siena, Italy
  • Otolaryngology Unit, University of Siena, Siena, Italy
  • AORN dei Colli Presidio Ospedaliero Cotugno, Azienda, Italy
  • Department of Internal Medicine, ASST Valtellina e Alto Lario, Sondrio, Italy
  • Study Coordinator Oncologia Medica e Ufficio Flussi Sondrio, Sondrio, Italy
  • Department of Infectious and Tropical Diseases, University of Padova, Padova, Italy
  • First Aid Department, Luigi Curto Hospital, Polla, Salerno, Italy
  • Local Health Unit-Pharmaceutical Department of Grosseto, Toscana Sud Est Local Health Unit, Grosseto, Italy
  • U.O.C. Laboratorio di Genetica Umana, IRCCS Istituto G. Gaslini, Genoa, Italy
  • Infectious Diseases Clinics, University of Modena and Reggio Emilia, Modena, Italy
  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/s41431-020-0691-z

    DOI

    http://dx.doi.org/10.1038/s41431-020-0691-z

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1129415224

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/32681121


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