2021
DOI: 10.1101/2021.03.23.21254158
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The polymorphism L412F in TLR3 inhibits autophagy and is a marker of severe COVID-19 in males

Abstract: The polymorphism L412F in TLR3 has been associated with several infectious diseases. However, the mechanism underlying this association is still unexplored. Here, we show that the L412F polymorphism in TLR3 is a marker of severity in COVID-19. This association increases in the sub-cohort of males. Impaired autophagy and reduced TNFα production was demonstrated in HEK293 cells transfected with TLR3-L412F plasmid and stimulated with specific agonist poly(I:C). A statistically significant reduced survival at 28 d… Show more

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Cited by 9 publications
(6 citation statements)
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“…Of note are the genes of surfactant proteins associated with severe disease: SFTDP gene encoding for SP-D protein and SFTPA1 gene encoding for SP-A protein; the signal transducer, PPP1R15A gene encoding for GADD34 protein. OAS1 and OAS3 related to RNA clearance of RNASEL (reported in panel A as having ultra-rare mutations; included here should also be the already reported TLR3412 [17]; the already reported SELP603 related to thrombosis [18]. Note: OAS1 haplotype A= c.1039-1G>A, (p.(Gly162Ser)), (p.(Ala352Thr)), (p.(Arg361Thr)), (p.(Gly397Arg)), (p.(Thr358Profs*26)).…”
Section: Resultsmentioning
confidence: 99%
See 3 more Smart Citations
“…Of note are the genes of surfactant proteins associated with severe disease: SFTDP gene encoding for SP-D protein and SFTPA1 gene encoding for SP-A protein; the signal transducer, PPP1R15A gene encoding for GADD34 protein. OAS1 and OAS3 related to RNA clearance of RNASEL (reported in panel A as having ultra-rare mutations; included here should also be the already reported TLR3412 [17]; the already reported SELP603 related to thrombosis [18]. Note: OAS1 haplotype A= c.1039-1G>A, (p.(Gly162Ser)), (p.(Ala352Thr)), (p.(Arg361Thr)), (p.(Gly397Arg)), (p.(Thr358Profs*26)).…”
Section: Resultsmentioning
confidence: 99%
“…2D and Supplementary Table 6a-b ). Among them are the L412F TLR3 and D603N SELP polymorphisms, already reported to be associated with the severe disease [17–18] and several coding polymorphisms in Linkage Disequilibrium (LD) with already reported genomic SNP, such as the ABO blood group, OAS1 - 3 genes, PPP1R15A gene and others [4]. In conclusion, considering their functions, genes involved in the immune and inflammatory responses, or those involved in the coagulation pathway and NK and T cell receptor, are to be considered natural candidates for severe or mild COVID-19.…”
Section: Resultsmentioning
confidence: 99%
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“…At the same time, several GWAS campaigns investigating the contribution of common genetic variation (Ellinghaus et al, 2020;Pairo-Castineira et al, 2020) to COVID-19 have provided robust support for the involvement of various genomic loci associated with COVID-19 severity and susceptibility, with the strongest nding for severity being located on chromosome 3. Up to now, the Italian GEN-COVID Multicenter Study contributed to the identi cation of rare variants (Baldassarri, Fava, et al, 2021;Fallerini, Daga, Mantovani, et al, 2021) and common polymorphisms Croci et al, 2021; associated with COVID-19 severity through the collection of more than two thousand biospecimens and clinical data from SARS-CoV-2-positive individuals (Daga et al, 2021) and whole exome sequencing (WES) analysis. The COVID-19 Host Genetics Initiative (COVID-19 HGI) (https://www.…”
Section: Introductionmentioning
confidence: 99%