Your browser doesn't support javascript.
ACE2 gene variants may underlie interindividual variability and susceptibility to COVID-19 in the Italian population.
Benetti, Elisa; Tita, Rossella; Spiga, Ottavia; Ciolfi, Andrea; Birolo, Giovanni; Bruselles, Alessandro; Doddato, Gabriella; Giliberti, Annarita; Marconi, Caterina; Musacchia, Francesco; Pippucci, Tommaso; Torella, Annalaura; Trezza, Alfonso; Valentino, Floriana; Baldassarri, Margherita; Brusco, Alfredo; Asselta, Rosanna; Bruttini, Mirella; Furini, Simone; Seri, Marco; Nigro, Vincenzo; Matullo, Giuseppe; Tartaglia, Marco; Mari, Francesca; Renieri, Alessandra; Pinto, Anna Maria.
  • Benetti E; Department of Medical Biotechnologies, University of Siena, Siena, Italy.
  • Tita R; Genetica Medica, Azienda Ospedaliera Universitaria Senese, Siena, Italy.
  • Spiga O; Department of Biotechnology, Chemistry and Pharmacy, University of Siena, Siena, Italy.
  • Ciolfi A; Genetics and Rare Diseases Research Division, Ospedale Pediatrico Bambino Gesù, IRCCS, Rome, Italy.
  • Birolo G; Department of Medical Sciences, University of Turin, Turin, Italy.
  • Bruselles A; Department of Oncology and Molecular Medicine, Istituto Superiore di Sanità, Rome, Italy.
  • Doddato G; Medical Genetics, University of Siena, Siena, Italy.
  • Giliberti A; Medical Genetics, University of Siena, Siena, Italy.
  • Marconi C; Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy.
  • Musacchia F; Telethon Institute of Genetics and Medicine, Pozzuoli, Italy.
  • Pippucci T; Sant'Orsola-Malpighi University Hospital, Bologna, Italy.
  • Torella A; Dipartimento di Medicina di Precisione, Università della Campania "Luigi Vanvitelli", Napoli, Italy.
  • Trezza A; Department of Biotechnology, Chemistry and Pharmacy, University of Siena, Siena, Italy.
  • Valentino F; Medical Genetics, University of Siena, Siena, Italy.
  • Baldassarri M; Medical Genetics, University of Siena, Siena, Italy.
  • Brusco A; Department of Medical Sciences, University of Turin, Turin, Italy.
  • Asselta R; Genetica Medica, Città della Salute e della Scienza, Torino, Italy.
  • Bruttini M; Department of Biomedical Sciences, Humanitas University, Rozzano, Milan, Italy.
  • Furini S; Humanitas Clinical and Research Center-IRCCS, Rozzano, Milan, Italy.
  • Seri M; Genetica Medica, Azienda Ospedaliera Universitaria Senese, Siena, Italy.
  • Nigro V; Medical Genetics, University of Siena, Siena, Italy.
  • Matullo G; Department of Medical Biotechnologies, University of Siena, Siena, Italy.
  • Tartaglia M; Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy.
  • Mari F; Sant'Orsola-Malpighi University Hospital, Bologna, Italy.
  • Renieri A; Dipartimento di Medicina di Precisione, Università della Campania "Luigi Vanvitelli", Napoli, Italy.
  • Pinto AM; Department of Medical Sciences, University of Turin, Turin, Italy.
Eur J Hum Genet ; 28(11): 1602-1614, 2020 11.
Article in English | MEDLINE | ID: covidwho-650252
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.
Subject(s)

Full text: Available Collection: International databases Database: MEDLINE Main subject: Pneumonia, Viral / Coronavirus Infections / Peptidyl-Dipeptidase A Type of study: Cohort study / Observational study / Prognostic study Topics: Variants Limits: Aged / Female / Humans / Male / Middle aged Country/Region as subject: Europa Language: English Journal: Eur J Hum Genet Journal subject: Genetics, Medical Year: 2020 Document Type: Article Affiliation country: S41431-020-0691-z

Similar

MEDLINE

...
LILACS

LIS


Full text: Available Collection: International databases Database: MEDLINE Main subject: Pneumonia, Viral / Coronavirus Infections / Peptidyl-Dipeptidase A Type of study: Cohort study / Observational study / Prognostic study Topics: Variants Limits: Aged / Female / Humans / Male / Middle aged Country/Region as subject: Europa Language: English Journal: Eur J Hum Genet Journal subject: Genetics, Medical Year: 2020 Document Type: Article Affiliation country: S41431-020-0691-z