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.
Chromosome 3 cluster rs11385942 variant links complement activation with severe COVID-19 / L. Valenti, S. Griffini, G. Lamorte, E. Grovetti, S.C. Uceda Renteria, F. Malvestiti, L. Scudeller, A. Bandera, F. Peyvandi, D. Prati, P. Meroni, M. Cugno. - In: JOURNAL OF AUTOIMMUNITY. - ISSN 0896-8411. - 117(2021 Feb).
|Titolo:||Chromosome 3 cluster rs11385942 variant links complement activation with severe COVID-19|
VALENTI, LUCA VITTORIO CARLO (Primo)
MERONI, PIERLUIGI (Penultimo)
CUGNO, MASSIMO (Ultimo) (Corresponding)
|Parole Chiave:||ABO group; C5a; Complement; COVID-19; rs11385942 G>GA variant; SC5b-9; ABO Blood-Group System; Aged; COVID-19; Chromosomes, Human, Pair 3; Complement Activation; Complement C5a; Disease Progression; Female; Gene Frequency; Genetic Association Studies; Genetic Predisposition to Disease; Hospitalization; Humans; Male; Middle Aged; Multigene Family; Polymorphism, Single Nucleotide; Risk; SARS-CoV-2; Viral Load; European Continental Ancestry Group; Genotype|
|Settore Scientifico Disciplinare:||Settore MED/09 - Medicina Interna|
|Data di pubblicazione:||feb-2021|
|Data ahead of print / Data di stampa:||9-gen-2021|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.1016/j.jaut.2021.102595|
|Appare nelle tipologie:||01 - Articolo su periodico|