Chromosome 3 cluster rs11385942 variant links complement activation with severe COVID-19.
J Autoimmun
; 117: 102595, 2021 02.
Article
in English
| MEDLINE | ID: covidwho-1014585
ABSTRACT
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.Keywords
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
ABO Blood-Group System
/
Chromosomes, Human, Pair 3
/
Multigene Family
/
Complement Activation
/
White People
/
COVID-19
/
Genotype
Type of study:
Experimental Studies
/
Prognostic study
/
Randomized controlled trials
Topics:
Variants
Limits:
Aged
/
Female
/
Humans
/
Male
/
Middle aged
Language:
English
Journal:
J Autoimmun
Journal subject:
Allergy and Immunology
Year:
2021
Document Type:
Article
Affiliation country:
J.jaut.2021.102595
Similar
MEDLINE
...
LILACS
LIS