Deletion of the NKG2C receptor encoding KLRC2 gene and HLA-E variants are risk factors for severe COVID-19.
Genet Med
; 23(5): 963-967, 2021 05.
Article
in English
| MEDLINE | ID: covidwho-1049962
ABSTRACT
PURPOSE:
Host genetic variants may contribute to severity of COVID-19. NKG2C+ NK cells are potent antiviral effector cells, potentially limiting the extent of SARS-CoV-2 infections. NKG2C is an activating NK cell receptor encoded by the KLRC2 gene, which binds to HLA-E on infected cells leading to NK cell activation. Heterozygous or homozygous KLRC2 deletion (KLRC2del) may naturally occur and is associated with a significantly lower or absent NKG2C expression level. In addition, HLA-E*0101/0103 genetic variants occur, caused by a single-nucleotide polymorphism. We therefore investigated whether the severity of COVID-19 is associated with these genetic variants.METHODS:
We investigated the distribution of KLRC2 deletion and HLA-E*0101/0103 allelic variants in a study cohort of 361 patients with either mild (N = 92) or severe (N = 269) COVID-19.RESULTS:
Especially the KLRC2del, and at a lower degree the HLA-E*0101, allele were significantly overrepresented in hospitalized patients (p = 0.0006 and p = 0.01), particularly in patients requiring intensive care (p < 0.0001 and p = 0.01), compared with patients with mild symptoms. Both genetic variants were independent risk factors for severe COVID-19.CONCLUSION:
Our data show that these genetic variants in the NKG2C/HLA-E axis have a significant impact on the development of severe SARS-CoV-2 infections, and may help to identify patients at high-risk for severe COVID-19.
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
NK Cell Lectin-Like Receptor Subfamily C
/
COVID-19
Type of study:
Cohort study
/
Observational study
/
Prognostic study
Topics:
Variants
Limits:
Humans
Language:
English
Journal:
Genet Med
Journal subject:
Genetics, Medical
Year:
2021
Document Type:
Article
Affiliation country:
S41436-020-01077-7
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