Association of Toll-like receptor 7 variants with life-threatening COVID-19 disease in males: findings from a nested case-control study.
Elife
; 102021 03 02.
Article
in English
| MEDLINE | ID: covidwho-1112866
ABSTRACT
Background:
Recently, loss-of-function variants in TLR7 were identified in two families in which COVID-19 segregates like an X-linked recessive disorder environmentally conditioned by SARS-CoV-2. We investigated whether the two families represent the tip of the iceberg of a subset of COVID-19 male patients.Methods:
This is a nested case-control study in which we compared male participants with extreme phenotype selected from the Italian GEN-COVID cohort of SARS-CoV-2-infected participants (<60 y, 79 severe cases versus 77 control cases). We applied the LASSO Logistic Regression analysis, considering only rare variants on young male subsets with extreme phenotype, picking up TLR7 as the most important susceptibility gene.Results:
Overall, we found TLR7 deleterious variants in 2.1% of severely affected males and in none of the asymptomatic participants. The functional gene expression profile analysis demonstrated a reduction in TLR7-related gene expression in patients compared with controls demonstrating an impairment in type I and II IFN responses.Conclusions:
Young males with TLR7 loss-of-function variants and severe COVID-19 represent a subset of male patients contributing to disease susceptibility in up to 2% of severe COVID-19.Funding:
Funded by private donors for the Host Genetics Research Project, the Intesa San Paolo for 2020 charity fund, and the Host Genetics Initiative. Clinical trial number NCT04549831.Keywords
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Polymorphism, Single Nucleotide
/
Toll-Like Receptor 7
/
COVID-19
Type of study:
Cohort study
/
Diagnostic study
/
Observational study
/
Prognostic study
/
Randomized controlled trials
Topics:
Variants
Limits:
Adult
/
Humans
/
Male
/
Middle aged
Country/Region as subject:
Europa
Language:
English
Year:
2021
Document Type:
Article
Affiliation country:
ELife.67569
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