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Sex-biased expression of the TLR7 gene in severe COVID-19 patients: Insights from transcriptomics and epigenomics
There is abundant epidemiological data indicating that the incidence of severe cases of coronavirus disease (COVID-19) is significantly higher in males than females worldwide. Moreover, genetic variation at the X-chromosome linked TLR7 gene has been associated with COVID-19 severity. It has been sug...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The Authors. Published by Elsevier Inc.
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9508271/ https://www.ncbi.nlm.nih.gov/pubmed/36152884 http://dx.doi.org/10.1016/j.envres.2022.114288 |
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author | Gómez-Carballa, A. Pardo-Seco, J. Pischedda, S. Rivero-Calle, I. Butler-Laporte, G. Richards, J.B. Viz-Lasheras, S. Martinón-Torres, F. Salas, A. |
author_facet | Gómez-Carballa, A. Pardo-Seco, J. Pischedda, S. Rivero-Calle, I. Butler-Laporte, G. Richards, J.B. Viz-Lasheras, S. Martinón-Torres, F. Salas, A. |
author_sort | Gómez-Carballa, A. |
collection | PubMed |
description | There is abundant epidemiological data indicating that the incidence of severe cases of coronavirus disease (COVID-19) is significantly higher in males than females worldwide. Moreover, genetic variation at the X-chromosome linked TLR7 gene has been associated with COVID-19 severity. It has been suggested that the sex-biased incidence of COVID-19 might be related to the fact that TLR7 escapes X-chromosome inactivation during early embryogenesis in females, thus encoding a doble dose of its gene product compared to males. We analyzed TLR7 expression in two acute phase cohorts of COVID-19 patients that used two different technological platforms, one of them in a multi-tissue context including saliva, nasal, and blood samples, and a third cohort that included different post-infection timepoints of long-COVID-19 patients. We additionally explored methylation patterns of TLR7 using epigenomic data from an independent cohort of COVID-19 patients stratified by severity and sex. In line with genome-wide association studies, we provide supportive evidence indicating that TLR7 has altered CpG methylation patterns and it is consistently downregulated in males compared to females in the most severe cases of COVID-19. |
format | Online Article Text |
id | pubmed-9508271 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | The Authors. Published by Elsevier Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-95082712022-09-26 Sex-biased expression of the TLR7 gene in severe COVID-19 patients: Insights from transcriptomics and epigenomics Gómez-Carballa, A. Pardo-Seco, J. Pischedda, S. Rivero-Calle, I. Butler-Laporte, G. Richards, J.B. Viz-Lasheras, S. Martinón-Torres, F. Salas, A. Environ Res Article There is abundant epidemiological data indicating that the incidence of severe cases of coronavirus disease (COVID-19) is significantly higher in males than females worldwide. Moreover, genetic variation at the X-chromosome linked TLR7 gene has been associated with COVID-19 severity. It has been suggested that the sex-biased incidence of COVID-19 might be related to the fact that TLR7 escapes X-chromosome inactivation during early embryogenesis in females, thus encoding a doble dose of its gene product compared to males. We analyzed TLR7 expression in two acute phase cohorts of COVID-19 patients that used two different technological platforms, one of them in a multi-tissue context including saliva, nasal, and blood samples, and a third cohort that included different post-infection timepoints of long-COVID-19 patients. We additionally explored methylation patterns of TLR7 using epigenomic data from an independent cohort of COVID-19 patients stratified by severity and sex. In line with genome-wide association studies, we provide supportive evidence indicating that TLR7 has altered CpG methylation patterns and it is consistently downregulated in males compared to females in the most severe cases of COVID-19. The Authors. Published by Elsevier Inc. 2022-12 2022-09-21 /pmc/articles/PMC9508271/ /pubmed/36152884 http://dx.doi.org/10.1016/j.envres.2022.114288 Text en © 2022 The Authors Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active. |
spellingShingle | Article Gómez-Carballa, A. Pardo-Seco, J. Pischedda, S. Rivero-Calle, I. Butler-Laporte, G. Richards, J.B. Viz-Lasheras, S. Martinón-Torres, F. Salas, A. Sex-biased expression of the TLR7 gene in severe COVID-19 patients: Insights from transcriptomics and epigenomics |
title | Sex-biased expression of the TLR7 gene in severe COVID-19 patients: Insights from transcriptomics and epigenomics |
title_full | Sex-biased expression of the TLR7 gene in severe COVID-19 patients: Insights from transcriptomics and epigenomics |
title_fullStr | Sex-biased expression of the TLR7 gene in severe COVID-19 patients: Insights from transcriptomics and epigenomics |
title_full_unstemmed | Sex-biased expression of the TLR7 gene in severe COVID-19 patients: Insights from transcriptomics and epigenomics |
title_short | Sex-biased expression of the TLR7 gene in severe COVID-19 patients: Insights from transcriptomics and epigenomics |
title_sort | sex-biased expression of the tlr7 gene in severe covid-19 patients: insights from transcriptomics and epigenomics |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9508271/ https://www.ncbi.nlm.nih.gov/pubmed/36152884 http://dx.doi.org/10.1016/j.envres.2022.114288 |
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