Analysis of ACE2 genetic variants in 131 Italian SARS-CoV-2-positive patients.
Antonio Novelli,Michela Biancolella,Paola Borgiani,Dario Cocciadiferro,Vito Luigi Colona,Maria Rosaria D'Apice,Paola Rogliani,Salvatore Zaffina,Francesca Leonardis,Andrea Campana,Massimiliano Raponi,Massimo Andreoni,Sandro Grelli,Giuseppe Novelli +13 more
TLDR
There is no strong evidence, in this cohort, of consistent association of ACE2 variants with COVID-19 severity, and it might speculate that rare susceptibility/resistant alleles could be located in the non-coding regions of the ACE2 gene, known to play a role in regulation of the gene activity.Abstract:
Coronaviruses (CoV) are a large family of viruses that are common in humans and many animal species. Animal coronaviruses rarely infect humans with the exceptions of the Middle East respiratory syndrome (
MERS-CoV
), the severe acute respiratory syndrome corona virus (SARS-CoV), and now SARS-CoV-2, which is the cause of the ongoing pandemic of coronavirus disease 2019 (COVID-19). Several studies suggested that genetic variants in the ACE2 gene may influence the host susceptibility or resistance to SARS-CoV-2 infection according to the functional role of ACE2 in human pathophysiology. However, many of these studies have been conducted in silico based on epidemiological and population data. We therefore investigated the occurrence of ACE2 variants in a cohort of 131 Italian unrelated individuals clinically diagnosed with COVID-19 and in an Italian control population, to evaluate a possible allelic association with COVID-19, by direct DNA analysis. As a pilot study, we analyzed, by whole-exome sequencing, genetic variants of ACE2 gene in 131 DNA samples of COVID-19 patients hospitalized at Tor Vergata University Hospital and at Bambino Gesu Children’s Hospital, Rome. We used a large control group consisting of 1000 individuals (500 males and 500 females). We identified three different germline variants: one intronic c.439+4G>A and two missense c.1888G>C p.(Asp630His) and c.2158A>G p.(Asn720Asp) in a total of 131 patients with a similar frequency in male and female. Thus far, only the c.1888G>C p.(Asp630His) variant shows a statistically different frequency compared to the ethnically matched populations. Therefore, further studies are needed in larger cohorts, since it was found only in one heterozygous COVID-19 patient. Our results suggest that there is no strong evidence, in our cohort, of consistent association of ACE2 variants with COVID-19 severity. We might speculate that rare susceptibility/resistant alleles could be located in the non-coding regions of the ACE2 gene, known to play a role in regulation of the gene activity.read more
Citations
More filters
Journal ArticleDOI
HLA allele frequencies and susceptibility to COVID-19 in a group of 99 Italian patients.
Antonio Novelli,Marco Andreani,Michela Biancolella,Laura Liberatoscioli,Chiara Passarelli,Vito Luigi Colona,Paola Rogliani,Francesca Leonardis,Andrea Campana,Rita Carsetti,Massimo Andreoni,Sergio Bernardini,Giuseppe Novelli,Franco Locatelli +13 more
TL;DR: The increased frequencies observed may contribute to identify potential markers of susceptibility to the disease, although controversial results on the role of single HLA alleles in COVID‐19 patients have been recently reported.
Journal ArticleDOI
Human genetic factors associated with susceptibility to SARS-CoV-2 infection and COVID-19 disease severity.
Cleo Anastassopoulou,Zoi Gkizarioti,George P. Patrinos,George P. Patrinos,Athanasios Tsakris +4 more
TL;DR: Determinants of differing severity of COVID-19 predominantly include components of the immune response to the virus, while determinant of differing susceptibility to SARS-CoV-2 mostly entail genes related to the initial stages of infection.
Journal ArticleDOI
COVID-19 and Genetic Variants of Protein Involved in the SARS-CoV-2 Entry into the Host Cells.
Andrea Latini,Emanuele Agolini,Antonio Novelli,Paola Borgiani,Rosalinda Giannini,Paolo Gravina,Andrea Smarrazzo,Mario Dauri,Massimo Andreoni,Paola Rogliani,Sergio Bernardini,Manuela Helmer-Citterich,Michela Biancolella,Giuseppe Novelli +13 more
TL;DR: Genetic variants in these genes could influence the entry of the SARS-CoV-2 and support the hypothesis that host genetic variability may contribute to the variability in infection susceptibility and severity.
Journal ArticleDOI
ACE2 polymorphism and susceptibility for SARS-CoV-2 infection and severity of COVID-19.
Birte Möhlendick,Kristina Schönfelder,Katharina Breuckmann,Carina Elsner,Nina Babel,Paul Balfanz,Edgar Dahl,Michael Dreher,David Fistera,Frank Herbstreit,Bodo Hölzer,Michael O. Koch,Matthias Kohnle,Nikolaus Marx,Joachim Risse,Karsten Schmidt,Sarah Skrzypczyk,Sivagurunathan Sutharsan,Christian Taube,Timm H. Westhoff,Karl-Heinz Jöckel,Ulf Dittmer,Winfried Siffert,Andreas Kribben +23 more
TL;DR: In this article, the association of SNPs with susceptibility for SARS-CoV-2 infection and the severity of COVID-19 was analyzed, showing that the GG genotype or G-allele was significantly associated with an almost two-fold increase in infection risk and a three-fold increased risk to develop serious disease.
Journal ArticleDOI
Polymorphisms of ACE (I/D) and ACE2 receptor gene (Rs2106809, Rs2285666) are not related to the clinical course of COVID-19: A case study.
Sevim Karakaş Çelik,Gunes Cakmak Genc,Nihal Pişkin,Bilgehan Açıkgöz,Bulent Altinsoy,Başak Kurucu İşsiz,Ahmet Dursun +6 more
TL;DR: In this article, the ACE gene insertion/deletion (I/D) polymorphism and ACE2 receptor gene rs2106809 and rs2285666 polymorphisms were determined using polymerase chain reaction (PCR) and PCR-based restriction fragment length polymorphism methods, respectively, in 155 COVID-19 patients who were divided into three groups according to clinical symptoms.
References
More filters
Journal ArticleDOI
A Novel Coronavirus from Patients with Pneumonia in China, 2019.
Na Zhu,Dingyu Zhang,Wenling Wang,Xingwang Li,Bo Yang,Jingdong Song,Xiang Zhao,Baoying Huang,Weifeng Shi,Roujian Lu,Peihua Niu,Faxian Zhan,Xuejun Ma,Dayan Wang,Wenbo Xu,Wenbo Xu,Guizhen Wu,George F. Gao,Wenjie Tan +18 more
TL;DR: Human airway epithelial cells were used to isolate a novel coronavirus, named 2019-nCoV, which formed a clade within the subgenus sarbecovirus, Orthocoronavirinae subfamily, which is the seventh member of the family of coronaviruses that infect humans.
Journal ArticleDOI
A pneumonia outbreak associated with a new coronavirus of probable bat origin
Peng Zhou,Xing-Lou Yang,Xian Guang Wang,Ben Hu,Lei Zhang,Wei Zhang,Hao Rui Si,Yan Zhu,Bei Li,Chao Lin Huang,Hui-Dong Chen,Jing Chen,Yun Luo,Hua Guo,Ren Di Jiang,Meiqin Liu,Ying Chen,Xu Rui Shen,Xi Wang,Xiao Shuang Zheng,Kai Zhao,Quanjiao Chen,Fei Deng,Lin Lin Liu,Bing Yan,Fa Xian Zhan,Yan-Yi Wang,Gengfu Xiao,Zhengli Shi +28 more
TL;DR: Identification and characterization of a new coronavirus (2019-nCoV), which caused an epidemic of acute respiratory syndrome in humans in Wuhan, China, and it is shown that this virus belongs to the species of SARSr-CoV, indicates that the virus is related to a bat coronav virus.
Journal ArticleDOI
A new coronavirus associated with human respiratory disease in China.
Fan Wu,Su Zhao,Bin Yu,Yan-Mei Chen,Wen Wang,Zhi gang Song,Yi Hu,Zhao Wu Tao,Jun Hua Tian,Yuan Yuan Pei,Ming Li Yuan,Yu Ling Zhang,Fa Hui Dai,Yi Liu,Qi Min Wang,Jiao Jiao Zheng,Lin Xu,Edward C. Holmes,Edward C. Holmes,Yong-Zhen Zhang,Yong-Zhen Zhang +20 more
TL;DR: Phylogenetic and metagenomic analyses of the complete viral genome of a new coronavirus from the family Coronaviridae reveal that the virus is closely related to a group of SARS-like coronaviruses found in bats in China.
Journal ArticleDOI
Cryo-EM structure of the 2019-nCoV spike in the prefusion conformation.
Daniel Wrapp,Nianshuang Wang,Kizzmekia S. Corbett,Jory A. Goldsmith,Ching-Lin Hsieh,Olubukola M. Abiona,Barney S. Graham,Jason S. McLellan +7 more
TL;DR: The authors show that this protein binds at least 10 times more tightly than the corresponding spike protein of severe acute respiratory syndrome (SARS)–CoV to their common host cell receptor, and test several published SARS-CoV RBD-specific monoclonal antibodies found that they do not have appreciable binding to 2019-nCoV S, suggesting that antibody cross-reactivity may be limited between the two RBDs.
Related Papers (5)
Genomewide Association Study of Severe Covid-19 with Respiratory Failure.
David Ellinghaus,Frauke Degenhardt,Luis Bujanda,Maria Buti,Agustín Albillos,Pietro Invernizzi,J. Fernández,Daniele Prati,Guido Baselli,Rosanna Asselta,Marit Mæhle Grimsrud,Chiara Milani,Fatima Aziz,Jan Christian Kässens,Sandra May,Mareike Wendorff,Lars Wienbrandt,Florian Uellendahl-Werth,Tenghao Zheng,Xiaoli Yi,Raúl de Pablo,Adolfo Garrido Chercoles,Adriana Palom,Alba Estela Garcia-Fernandez,Francisco Rodriguez-Frias,Alberto Zanella,Alessandra Bandera,Alessandro Protti,Alessio Aghemo,Ana Lleo,Andrea Biondi,Andrea Caballero-Garralda,Andrea Gori,Anja Tanck,Anna Carreras Nolla,Anna Latiano,Anna Ludovica Fracanzani,Anna Peschuck,Antonio Julià,Antonio Pesenti,Antonio Voza,David Jiménez,Beatriz Mateos,Beatriz Nafria Jimenez,Carmen Quereda,Cinzia Paccapelo,Christoph Gassner,Claudio Angelini,Cristina Cea,Aurora Solier,David Pestana,Eduardo Muñiz-Diaz,Elena Sandoval,Elvezia Maria Paraboschi,Enrique Navas,Félix García Sánchez,Ferruccio Ceriotti,F. Martinelli-Boneschi,Flora Peyvandi,Francesco Blasi,Luis Téllez,Albert Blanco-Grau,Georg Hemmrich-Stanisak,Giacomo Grasselli,Giorgio Costantino,Giulia Cardamone,Giuseppe Foti,Serena Aneli,Hayato Kurihara,Hesham ElAbd,Ilaria My,Iván Galván-Femenía,Javier Martin,Jeanette Erdmann,José Ferrusquía-Acosta,Koldo Garcia-Etxebarria,Laura Izquierdo-Sanchez,Laura Rachele Bettini,Lauro Sumoy,Leonardo Terranova,Leticia Moreira,Luigi Santoro,Luigia Scudeller,Francisco Mesonero,Luisa Roade,Malte C. Rühlemann,Marco Schaefer,Maria Carrabba,Mar Riveiro-Barciela,Maria Eloina Figuera Basso,Maria Grazia Valsecchi,María Hernández-Tejero,Marialbert Acosta-Herrera,Mariella D'Angiò,Marina Baldini,Marina Cazzaniga,Martin Schulzky,Maurizio Cecconi,Michael Wittig,Michele Ciccarelli,Miguel Rodríguez-Gandía,Monica Bocciolone,Monica Miozzo,Nicola Montano,Nicole Braun,Nicoletta Sacchi,Nilda Martinez,Onur Özer,Orazio Palmieri,Paola Faverio,Paoletta Preatoni,Paolo Bonfanti,Paolo Omodei,Paolo Tentorio,Pedro Castro,Pedro M. Rodrigues,Aaron Blandino Ortiz,Rafael de Cid,Ricard Ferrer,Roberta Gualtierotti,Rosa Nieto,Siegfried Goerg,Salvatore Badalamenti,Sara Marsal,Giuseppe Matullo,Serena Pelusi,Simonas Juzenas,Stefano Aliberti,Valter Monzani,Victor Moreno,Tanja Wesse,Tobias L. Lenz,Tomás Pumarola,Valeria Rimoldi,Silvano Bosari,Wolfgang Albrecht,Wolfgang Peter,Manuel Romero-Gómez,Mauro D'Amato,Stefano Duga,Jesus M. Banales,Johannes R. Hov,Trine Folseraas,Luca Valenti,Andre Franke,Tom H. Karlsen +145 more
Inborn errors of type I IFN immunity in patients with life-threatening COVID-19
Qian Zhang,Paul Bastard,Paul Bastard,Zhiyong Liu,Jérémie Le Pen,Marcela Moncada-Vélez,Jie Chen,Masato Ogishi,Ira K. D. Sabli,Stephanie Hodeib,Cecilia B. Korol,Jérémie Rosain,Jérémie Rosain,Kaya Bilguvar,Junqiang Ye,Alexandre Bolze,Benedetta Bigio,Rui Yang,Andrés Augusto Arias,Andrés Augusto Arias,Qinhua Zhou,Yu Zhang,Fanny Onodi,Sarantis Korniotis,Léa Karpf,Quentin Philippot,Quentin Philippot,Marwa Chbihi,Marwa Chbihi,Lucie Bonnet-Madin,Karim Dorgham,Nikaïa Smith,William M. Schneider,Brandon S. Razooky,Hans-Heinrich Hoffmann,Eleftherios Michailidis,Leen Moens,Ji Eun Han,Lazaro Lorenzo,Lazaro Lorenzo,Lucy Bizien,Lucy Bizien,Philip Meade,Anna-Lena Neehus,Anna-Lena Neehus,Aileen Camille Ugurbil,Aurélien Corneau,Gaspard Kerner,Gaspard Kerner,Peng Zhang,Franck Rapaport,Yoann Seeleuthner,Yoann Seeleuthner,Jeremy Manry,Jeremy Manry,Cécile Masson,Yohann Schmitt,Agatha Schlüter,Tom Le Voyer,Tom Le Voyer,Taushif Khan,Juan Li,Jacques Fellay,Jacques Fellay,Lucie Roussel,Mohammad Shahrooei,Mohammed F. Alosaimi,Davood Mansouri,Haya Al-Saud,Fahd Al-Mulla,Feras M. Almourfi,Saleh Al-Muhsen,Fahad Alsohime,Saeed Al Turki,Rana Hasanato,Diederik van de Beek,Andrea Biondi,Laura Rachele Bettini,Mariella D'Angiò,Paolo Bonfanti,Luisa Imberti,Alessandra Sottini,Simone Paghera,Eugenia Quiros-Roldan,Camillo Rossi,Andrew J. Oler,Miranda F. Tompkins,Camille Alba,Isabelle Vandernoot,Jean-Christophe Goffard,Guillaume Smits,Isabelle Migeotte,Filomeen Haerynck,Pere Soler-Palacín,Andrea Martín-Nalda,Roger Colobran,Pierre-Emmanuel Morange,Sevgi Keles,Fatma Çölkesen,Tayfun Ozcelik,Kadriye Kart Yaşar,Sevtap Şenoğlu,Şemsi Nur Karabela,Carlos Rodríguez-Gallego,Giuseppe Novelli,Sami Hraiech,Yacine Tandjaoui-Lambiotte,Xavier Duval,Xavier Duval,Cédric Laouénan,Cédric Laouénan,Covid-Storm Clinicians§,Covid Clinicians,CoV-Contact Cohort§,CoV-Contact Cohort§,Amsterdam Umc Covid Biobank,Covid Human Genetic Effort,Niaid-Usuhs,Niaid-Usuhs,Niaid-Usuhs,Andrew L. Snow,Clifton L. Dalgard,Joshua D. Milner,Donald C. Vinh,Donald C. Vinh,Trine H. Mogensen,Trine H. Mogensen,Nico Marr,András N Spaan,András N Spaan,András N Spaan,Bertrand Boisson,Bertrand Boisson,Bertrand Boisson,Stéphanie Boisson-Dupuis,Jacinta Bustamante,Jacinta Bustamante,Jacinta Bustamante,Anne Puel,Michael J. Ciancanelli,Isabelle Meyts,Tom Maniatis,Vassili Soumelis,Ali Amara,Ali Amara,Michel C. Nussenzweig,Adolfo García-Sastre,Florian Krammer,Aurora Pujol,Darragh Duffy,Darragh Duffy,Richard P. Lifton,Richard P. Lifton,Richard P. Lifton,Shen-Ying Zhang,Guy Gorochov,Guy Gorochov,Guy Gorochov,Vivien Béziat,Vivien Béziat,Vivien Béziat,Emmanuelle Jouanguy,Vanessa Sancho-Shimizu,Charles M. Rice,Charles M. Rice,Charles M. Rice,Laurent Abel,Luigi D. Notarangelo,Luigi D. Notarangelo,Luigi D. Notarangelo,Aurélie Cobat,Helen C. Su,Jean-Laurent Casanova +172 more
ACE2 gene variants may underlie interindividual variability and susceptibility to COVID-19 in the Italian population.
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,Alessandra Renieri,Anna Maria Pinto +25 more
Presence of Genetic Variants Among Young Men With Severe COVID-19.
Caspar I van der Made,Annet Simons,Janneke H M Schuurs-Hoeijmakers,Guus R. M. van den Heuvel,Tuomo Mantere,Simone Kersten,Rosanne C. van Deuren,Marloes Steehouwer,Simon V. van Reijmersdal,Martin Jaeger,Tom Hofste,Galuh D.N. Astuti,Jordi Corominas Galbany,Vyne van der Schoot,Hans van der Hoeven,Eva Klijn,Catrien van den Meer,Jeroen Fiddelaers,Quirijn de Mast,Chantal P. Bleeker-Rovers,Leo A. B. Joosten,Helger G. Yntema,Christian Gilissen,Marcel R. Nelen,Jos W. M. van der Meer,Han G. Brunner,Mihai G. Netea,Frank L. van de Veerdonk,Alexander Hoischen +28 more