FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W4206385514> ?p ?o ?g. }

• W4206385514 endingPage "103333" @default.
• W4206385514 startingPage "103333" @default.
• W4206385514 abstract "The human protein transmembrane protease serine type 2 (TMPRSS2) plays a key role in SARS-CoV-2 infection, as it is required to activate the virus' spike protein, facilitating entry into target cells. We hypothesized that naturally-occurring TMPRSS2 human genetic variants affecting the structure and function of the TMPRSS2 protein may modulate the severity of SARS-CoV-2 infection.We focused on the only common TMPRSS2 non-synonymous variant predicted to be damaging (rs12329760 C>T, p.V160M), which has a minor allele frequency ranging from 0.14 in Ashkenazi Jewish to 0.38 in East Asians. We analysed the association between the rs12329760 and COVID-19 severity in 2,244 critically ill patients with COVID-19 from 208 UK intensive care units recruited as part of the GenOMICC (Genetics Of Mortality In Critical Care) study. Logistic regression analyses were adjusted for sex, age and deprivation index. For in vitro studies, HEK293 cells were co-transfected with ACE2 and either TMPRSS2 wild type or mutant (TMPRSS2V160M). A SARS-CoV-2 pseudovirus entry assay was used to investigate the ability of TMPRSS2V160M to promote viral entry.We show that the T allele of rs12329760 is associated with a reduced likelihood of developing severe COVID-19 (OR 0.87, 95%CI:0.79-0.97, p = 0.01). This association was stronger in homozygous individuals when compared to the general population (OR 0.65, 95%CI:0.50-0.84, p = 1.3 × 10-3). We demonstrate in vitro that this variant, which causes the amino acid substitution valine to methionine, affects the catalytic activity of TMPRSS2 and is less able to support SARS-CoV-2 spike-mediated entry into cells.TMPRSS2 rs12329760 is a common variant associated with a significantly decreased risk of severe COVID-19. Further studies are needed to assess the expression of TMPRSS2 across different age groups. Moreover, our results identify TMPRSS2 as a promising drug target, with a potential role for camostat mesilate, a drug approved for the treatment of chronic pancreatitis and postoperative reflux esophagitis, in the treatment of COVID-19. Clinical trials are needed to confirm this." @default.
• W4206385514 created "2022-01-25" @default.
• W4206385514 creator A5023619547 @default.
• W4206385514 creator A5026122068 @default.
• W4206385514 creator A5026924923 @default.
• W4206385514 creator A5028879635 @default.
• W4206385514 creator A5030523023 @default.
• W4206385514 creator A5032389175 @default.
• W4206385514 creator A5034767660 @default.
• W4206385514 creator A5038353299 @default.
• W4206385514 creator A5047229923 @default.
• W4206385514 creator A5068283266 @default.
• W4206385514 creator A5071925173 @default.
• W4206385514 creator A5090402295 @default.
• W4206385514 creator A5090497008 @default.
• W4206385514 date "2022-05-01" @default.
• W4206385514 modified "2023-10-09" @default.
• W4206385514 title "A common TMPRSS2 variant has a protective effect against severe COVID-19" @default.
• W4206385514 cites W1656256413 @default.
• W4206385514 cites W1803102843 @default.
• W4206385514 cites W1977056120 @default.
• W4206385514 cites W1978884666 @default.
• W4206385514 cites W1987507232 @default.
• W4206385514 cites W1998964868 @default.
• W4206385514 cites W2023490488 @default.
• W4206385514 cites W2031843235 @default.
• W4206385514 cites W2059145105 @default.
• W4206385514 cites W2064076043 @default.
• W4206385514 cites W2064244952 @default.
• W4206385514 cites W2065596960 @default.
• W4206385514 cites W2070827084 @default.
• W4206385514 cites W2073836327 @default.
• W4206385514 cites W2081719521 @default.
• W4206385514 cites W2086493164 @default.
• W4206385514 cites W2101506295 @default.
• W4206385514 cites W2124200027 @default.
• W4206385514 cites W2128379747 @default.
• W4206385514 cites W2133520037 @default.
• W4206385514 cites W2140674451 @default.
• W4206385514 cites W2149393182 @default.
• W4206385514 cites W2161623759 @default.
• W4206385514 cites W2195303995 @default.
• W4206385514 cites W2330592952 @default.
• W4206385514 cites W2795386708 @default.
• W4206385514 cites W2936956377 @default.
• W4206385514 cites W2950099124 @default.
• W4206385514 cites W2964533563 @default.
• W4206385514 cites W3004280078 @default.
• W4206385514 cites W3009912996 @default.
• W4206385514 cites W3015134137 @default.
• W4206385514 cites W3020646040 @default.
• W4206385514 cites W3022435472 @default.
• W4206385514 cites W3022894063 @default.
• W4206385514 cites W3024287440 @default.
• W4206385514 cites W3033154947 @default.
• W4206385514 cites W3036779511 @default.
• W4206385514 cites W3041318796 @default.
• W4206385514 cites W3042860993 @default.
• W4206385514 cites W3046214948 @default.
• W4206385514 cites W3047533598 @default.
• W4206385514 cites W3081058758 @default.
• W4206385514 cites W3087862874 @default.
• W4206385514 cites W3088256443 @default.
• W4206385514 cites W3103625761 @default.
• W4206385514 cites W3104171425 @default.
• W4206385514 cites W3104557298 @default.
• W4206385514 cites W3111106539 @default.
• W4206385514 cites W3115751469 @default.
• W4206385514 cites W3118947400 @default.
• W4206385514 cites W3129019794 @default.
• W4206385514 cites W3133812656 @default.
• W4206385514 cites W3155237975 @default.
• W4206385514 cites W3155889931 @default.
• W4206385514 cites W3156990363 @default.
• W4206385514 cites W3159140204 @default.
• W4206385514 cites W3177828909 @default.
• W4206385514 cites W3191743264 @default.
• W4206385514 cites W4210702584 @default.
• W4206385514 doi "https://doi.org/10.1016/j.retram.2022.103333" @default.
• W4206385514 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/35104687" @default.
• W4206385514 hasPublicationYear "2022" @default.
• W4206385514 type Work @default.
• W4206385514 citedByCount "26" @default.
• W4206385514 countsByYear W42063855142022 @default.
• W4206385514 countsByYear W42063855142023 @default.
• W4206385514 crossrefType "journal-article" @default.
• W4206385514 hasAuthorship W4206385514A5023619547 @default.
• W4206385514 hasAuthorship W4206385514A5026122068 @default.
• W4206385514 hasAuthorship W4206385514A5026924923 @default.
• W4206385514 hasAuthorship W4206385514A5028879635 @default.
• W4206385514 hasAuthorship W4206385514A5030523023 @default.
• W4206385514 hasAuthorship W4206385514A5032389175 @default.
• W4206385514 hasAuthorship W4206385514A5034767660 @default.
• W4206385514 hasAuthorship W4206385514A5038353299 @default.
• W4206385514 hasAuthorship W4206385514A5047229923 @default.
• W4206385514 hasAuthorship W4206385514A5068283266 @default.
• W4206385514 hasAuthorship W4206385514A5071925173 @default.
• W4206385514 hasAuthorship W4206385514A5090402295 @default.

• next