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Germline rare variants of lectin pathway genes predispose to asymptomatic SARS-CoV-2 infection in elderly individuals
PURPOSE: Emerging evidence suggest that infection-dependent hyperactivation of complement system (CS) may worsen COVID-19 outcome. We investigated the role of predicted high impact rare variants — referred as qualifying variants (QVs) — of CS genes in predisposing asymptomatic COVID-19 in elderly in...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The Authors. Published by Elsevier Inc. on behalf of American College of Medical Genetics and Genomics.
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9068606/ https://www.ncbi.nlm.nih.gov/pubmed/35511137 http://dx.doi.org/10.1016/j.gim.2022.04.007 |
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author | D’Alterio, Giuseppe Lasorsa, Vito Alessandro Bonfiglio, Ferdinando Cantalupo, Sueva Rosato, Barbara Eleni Andolfo, Immacolata Russo, Roberta Esposito, Umberto Frisso, Giulia Abete, Pasquale Cassese, Gian Marco Servillo, Giuseppe Gentile, Ivan Piscopo, Carmelo Della Monica, Matteo Fiorentino, Giuseppe Boccia, Angelo Paolella, Giovanni Ferrucci, Veronica de Antonellis, Pasqualino Siciliano, Roberto Asadzadeh, Fathem Cerino, Pellegrino Buonerba, Carlo Pierri, Biancamaria Zollo, Massimo Iolascon, Achille Capasso, Mario |
author_facet | D’Alterio, Giuseppe Lasorsa, Vito Alessandro Bonfiglio, Ferdinando Cantalupo, Sueva Rosato, Barbara Eleni Andolfo, Immacolata Russo, Roberta Esposito, Umberto Frisso, Giulia Abete, Pasquale Cassese, Gian Marco Servillo, Giuseppe Gentile, Ivan Piscopo, Carmelo Della Monica, Matteo Fiorentino, Giuseppe Boccia, Angelo Paolella, Giovanni Ferrucci, Veronica de Antonellis, Pasqualino Siciliano, Roberto Asadzadeh, Fathem Cerino, Pellegrino Buonerba, Carlo Pierri, Biancamaria Zollo, Massimo Iolascon, Achille Capasso, Mario |
author_sort | D’Alterio, Giuseppe |
collection | PubMed |
description | PURPOSE: Emerging evidence suggest that infection-dependent hyperactivation of complement system (CS) may worsen COVID-19 outcome. We investigated the role of predicted high impact rare variants — referred as qualifying variants (QVs) — of CS genes in predisposing asymptomatic COVID-19 in elderly individuals, known to be more susceptible to severe disease. METHODS: Exploiting exome sequencing data and 56 CS genes, we performed a gene-based collapsing test between 164 asymptomatic subjects (aged ≥60 years) and 56,885 European individuals from the Genome Aggregation Database. We replicated this test comparing the same asymptomatic individuals with 147 hospitalized patients with COVID-19. RESULTS: We found an enrichment of QVs in 3 genes (MASP1, COLEC11, and COLEC10), which belong to the lectin pathway, in the asymptomatic cohort. Analyses of complement activity in serum showed decreased activity of lectin pathway in asymptomatic individuals with QVs. Finally, we found allelic variants associated with asymptomatic COVID-19 phenotype and with a decreased expression of MASP1, COLEC11, and COLEC10 in lung tissue. CONCLUSION: This study suggests that genetic rare variants can protect from severe COVID-19 by mitigating the activity of lectin pathway and prothrombin. The genetic data obtained through ES of 786 asymptomatic and 147 hospitalized individuals are publicly available at http://espocovid.ceinge.unina.it/ |
format | Online Article Text |
id | pubmed-9068606 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | The Authors. Published by Elsevier Inc. on behalf of American College of Medical Genetics and Genomics. |
record_format | MEDLINE/PubMed |
spelling | pubmed-90686062022-05-04 Germline rare variants of lectin pathway genes predispose to asymptomatic SARS-CoV-2 infection in elderly individuals D’Alterio, Giuseppe Lasorsa, Vito Alessandro Bonfiglio, Ferdinando Cantalupo, Sueva Rosato, Barbara Eleni Andolfo, Immacolata Russo, Roberta Esposito, Umberto Frisso, Giulia Abete, Pasquale Cassese, Gian Marco Servillo, Giuseppe Gentile, Ivan Piscopo, Carmelo Della Monica, Matteo Fiorentino, Giuseppe Boccia, Angelo Paolella, Giovanni Ferrucci, Veronica de Antonellis, Pasqualino Siciliano, Roberto Asadzadeh, Fathem Cerino, Pellegrino Buonerba, Carlo Pierri, Biancamaria Zollo, Massimo Iolascon, Achille Capasso, Mario Genet Med Article PURPOSE: Emerging evidence suggest that infection-dependent hyperactivation of complement system (CS) may worsen COVID-19 outcome. We investigated the role of predicted high impact rare variants — referred as qualifying variants (QVs) — of CS genes in predisposing asymptomatic COVID-19 in elderly individuals, known to be more susceptible to severe disease. METHODS: Exploiting exome sequencing data and 56 CS genes, we performed a gene-based collapsing test between 164 asymptomatic subjects (aged ≥60 years) and 56,885 European individuals from the Genome Aggregation Database. We replicated this test comparing the same asymptomatic individuals with 147 hospitalized patients with COVID-19. RESULTS: We found an enrichment of QVs in 3 genes (MASP1, COLEC11, and COLEC10), which belong to the lectin pathway, in the asymptomatic cohort. Analyses of complement activity in serum showed decreased activity of lectin pathway in asymptomatic individuals with QVs. Finally, we found allelic variants associated with asymptomatic COVID-19 phenotype and with a decreased expression of MASP1, COLEC11, and COLEC10 in lung tissue. CONCLUSION: This study suggests that genetic rare variants can protect from severe COVID-19 by mitigating the activity of lectin pathway and prothrombin. The genetic data obtained through ES of 786 asymptomatic and 147 hospitalized individuals are publicly available at http://espocovid.ceinge.unina.it/ The Authors. Published by Elsevier Inc. on behalf of American College of Medical Genetics and Genomics. 2022-08 2022-05-05 /pmc/articles/PMC9068606/ /pubmed/35511137 http://dx.doi.org/10.1016/j.gim.2022.04.007 Text en © 2022 The Authors Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active. |
spellingShingle | Article D’Alterio, Giuseppe Lasorsa, Vito Alessandro Bonfiglio, Ferdinando Cantalupo, Sueva Rosato, Barbara Eleni Andolfo, Immacolata Russo, Roberta Esposito, Umberto Frisso, Giulia Abete, Pasquale Cassese, Gian Marco Servillo, Giuseppe Gentile, Ivan Piscopo, Carmelo Della Monica, Matteo Fiorentino, Giuseppe Boccia, Angelo Paolella, Giovanni Ferrucci, Veronica de Antonellis, Pasqualino Siciliano, Roberto Asadzadeh, Fathem Cerino, Pellegrino Buonerba, Carlo Pierri, Biancamaria Zollo, Massimo Iolascon, Achille Capasso, Mario Germline rare variants of lectin pathway genes predispose to asymptomatic SARS-CoV-2 infection in elderly individuals |
title | Germline rare variants of lectin pathway genes predispose to asymptomatic SARS-CoV-2 infection in elderly individuals |
title_full | Germline rare variants of lectin pathway genes predispose to asymptomatic SARS-CoV-2 infection in elderly individuals |
title_fullStr | Germline rare variants of lectin pathway genes predispose to asymptomatic SARS-CoV-2 infection in elderly individuals |
title_full_unstemmed | Germline rare variants of lectin pathway genes predispose to asymptomatic SARS-CoV-2 infection in elderly individuals |
title_short | Germline rare variants of lectin pathway genes predispose to asymptomatic SARS-CoV-2 infection in elderly individuals |
title_sort | germline rare variants of lectin pathway genes predispose to asymptomatic sars-cov-2 infection in elderly individuals |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9068606/ https://www.ncbi.nlm.nih.gov/pubmed/35511137 http://dx.doi.org/10.1016/j.gim.2022.04.007 |
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