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Chromosome 3 cluster rs11385942 variant links complement activation with severe COVID-19
BACKGROUND: Genetic variation at a multigene cluster at chromosome 3p21.31 and the ABO blood group have been associated with the risk of developing severe COVID-19, but the mechanism remains unclear. Complement activation has been associated with COVID-19 severity. OBJECTIVE: The aim of this study w...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier Ltd.
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7796659/ https://www.ncbi.nlm.nih.gov/pubmed/33453462 http://dx.doi.org/10.1016/j.jaut.2021.102595 |
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author | Valenti, Luca Griffini, Samantha Lamorte, Giuseppe Grovetti, Elena Uceda Renteria, Sara Colonia Malvestiti, Francesco Scudeller, Luigia Bandera, Alessandra Peyvandi, Flora Prati, Daniele Meroni, Pierluigi Cugno, Massimo |
author_facet | Valenti, Luca Griffini, Samantha Lamorte, Giuseppe Grovetti, Elena Uceda Renteria, Sara Colonia Malvestiti, Francesco Scudeller, Luigia Bandera, Alessandra Peyvandi, Flora Prati, Daniele Meroni, Pierluigi Cugno, Massimo |
author_sort | Valenti, Luca |
collection | PubMed |
description | BACKGROUND: Genetic variation at a multigene cluster at chromosome 3p21.31 and the ABO blood group have been associated with the risk of developing severe COVID-19, but the mechanism remains unclear. Complement activation has been associated with COVID-19 severity. OBJECTIVE: The aim of this study was to examine whether chromosome 3p21.31 and the ABO variants are linked to the activation of the complement cascade in COVID-19 patients. METHODS: We considered 72 unrelated European hospitalized patients with genetic data and evaluation of circulating C5a and soluble terminal complement complex C5b-9 (SC5b-9). Twenty-six (36.1%) patients carried the rs11385942 G>GA variant and 44 (66.1%) non-O blood group associated with increased risk of severe COVID-19. RESULTS: C5a and SC5-b9 plasma levels were higher in rs11385949 GA carriers than in non-carriers (P = 0.041 and P = 0.012, respectively), while C5a levels were higher in non-O group than in O group patients (P = 0.019). The association between rs11385949 and SC5b-9 remained significant after adjustment for ABO and disease severity (P = 0.004) and further correction for C5a (P = 0.018). There was a direct relationship between upper airways viral load and SC5b-9 in carriers of the rs11385949 risk allele (P = 0.032), which was not observed in non-carriers. CONCLUSIONS: The rs11385949 G>GA variant, tagging the chromosome 3 gene cluster variation and predisposing to severe COVID-19, is associated with enhanced complement activation, both with C5a and terminal complement complex, while non-O blood group with C5a levels. These findings provide a link between genetic susceptibility to more severe COVID-19 and complement activation. |
format | Online Article Text |
id | pubmed-7796659 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Elsevier Ltd. |
record_format | MEDLINE/PubMed |
spelling | pubmed-77966592021-01-11 Chromosome 3 cluster rs11385942 variant links complement activation with severe COVID-19 Valenti, Luca Griffini, Samantha Lamorte, Giuseppe Grovetti, Elena Uceda Renteria, Sara Colonia Malvestiti, Francesco Scudeller, Luigia Bandera, Alessandra Peyvandi, Flora Prati, Daniele Meroni, Pierluigi Cugno, Massimo J Autoimmun Article BACKGROUND: Genetic variation at a multigene cluster at chromosome 3p21.31 and the ABO blood group have been associated with the risk of developing severe COVID-19, but the mechanism remains unclear. Complement activation has been associated with COVID-19 severity. OBJECTIVE: The aim of this study was to examine whether chromosome 3p21.31 and the ABO variants are linked to the activation of the complement cascade in COVID-19 patients. METHODS: We considered 72 unrelated European hospitalized patients with genetic data and evaluation of circulating C5a and soluble terminal complement complex C5b-9 (SC5b-9). Twenty-six (36.1%) patients carried the rs11385942 G>GA variant and 44 (66.1%) non-O blood group associated with increased risk of severe COVID-19. RESULTS: C5a and SC5-b9 plasma levels were higher in rs11385949 GA carriers than in non-carriers (P = 0.041 and P = 0.012, respectively), while C5a levels were higher in non-O group than in O group patients (P = 0.019). The association between rs11385949 and SC5b-9 remained significant after adjustment for ABO and disease severity (P = 0.004) and further correction for C5a (P = 0.018). There was a direct relationship between upper airways viral load and SC5b-9 in carriers of the rs11385949 risk allele (P = 0.032), which was not observed in non-carriers. CONCLUSIONS: The rs11385949 G>GA variant, tagging the chromosome 3 gene cluster variation and predisposing to severe COVID-19, is associated with enhanced complement activation, both with C5a and terminal complement complex, while non-O blood group with C5a levels. These findings provide a link between genetic susceptibility to more severe COVID-19 and complement activation. Elsevier Ltd. 2021-02 2021-01-09 /pmc/articles/PMC7796659/ /pubmed/33453462 http://dx.doi.org/10.1016/j.jaut.2021.102595 Text en © 2021 Elsevier Ltd. All rights reserved. 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 Valenti, Luca Griffini, Samantha Lamorte, Giuseppe Grovetti, Elena Uceda Renteria, Sara Colonia Malvestiti, Francesco Scudeller, Luigia Bandera, Alessandra Peyvandi, Flora Prati, Daniele Meroni, Pierluigi Cugno, Massimo Chromosome 3 cluster rs11385942 variant links complement activation with severe COVID-19 |
title | Chromosome 3 cluster rs11385942 variant links complement activation with severe COVID-19 |
title_full | Chromosome 3 cluster rs11385942 variant links complement activation with severe COVID-19 |
title_fullStr | Chromosome 3 cluster rs11385942 variant links complement activation with severe COVID-19 |
title_full_unstemmed | Chromosome 3 cluster rs11385942 variant links complement activation with severe COVID-19 |
title_short | Chromosome 3 cluster rs11385942 variant links complement activation with severe COVID-19 |
title_sort | chromosome 3 cluster rs11385942 variant links complement activation with severe covid-19 |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7796659/ https://www.ncbi.nlm.nih.gov/pubmed/33453462 http://dx.doi.org/10.1016/j.jaut.2021.102595 |
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