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Environ Res . Sex-biased expression of the TLR7 gene in severe COVID-19 patients: Insights from transcriptomics and epigenomics

tetano

Editor, Senior Moderator
Environ Res


. 2022 Sep 21;114288.
doi: 10.1016/j.envres.2022.114288. Online ahead of print.
Sex-biased expression of the TLR7 gene in severe COVID-19 patients: Insights from transcriptomics and epigenomics


A Gómez-Carballa[SUP] 1 [/SUP], J Pardo-Seco[SUP] 1 [/SUP], S Pischedda[SUP] 1 [/SUP], I Rivero-Calle[SUP] 2 [/SUP], G Butler-Laporte[SUP] 3 [/SUP], J B Richards[SUP] 3 [/SUP], S Viz-Lasheras[SUP] 1 [/SUP], F Martinón-Torres[SUP] 2 [/SUP], A Salas[SUP] 4 [/SUP], GENDRES network



Affiliations

Abstract

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 sites and is consistently downregulated in males compared to females in the most severe cases of COVID-19.

Keywords: COVID-19; DNA methylation; Epigenomics; Host; Long-COVID-19; RNAseq; TLR7; Transcriptomics; n-Counter.
 
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