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

被引:11
作者
Gomez-Carballa, A. [1 ,2 ,3 ,4 ]
Pardo-Seco, J. [1 ,2 ,3 ,4 ]
Pischedda, S. [1 ,2 ,3 ,4 ]
Rivero-Calle, I [1 ,2 ,5 ]
Butler-Laporte, G. [6 ,7 ]
Richards, J. B. [6 ,7 ]
Viz-Lasheras, S. [1 ,2 ,3 ,4 ]
Martinon-Torres, F. [1 ,2 ,5 ]
Salas, A. [1 ,2 ,3 ,4 ]
机构
[1] Univ Santiago de Compostela, Inst Invest Sanitaria IDIS, Genet Vaccines & Infect Res Grp GENVIP, Santiago De Compostela, Spain
[2] Ctr Invest Biomed Red Enfermedades Resp CIBER ES, Madrid, Spain
[3] Univ Santiago de Compostela, Unidade Xenet, Inst Ciencias Forenses, Fac Med, Santiago De Compostela, Spain
[4] Hosp Clin Univ Santiago SERGAS, GenPoB Res Grp, Inst Invest Sanitaria IDIS, Galicia, Spain
[5] Hosp Clin Univ Santiago de Compostela, Dept Pediat, Translat Pediat & Infect Dis, Santiago De Compostela, Spain
[6] McGill Univ, Dept Epidemiol Biostat & Occupat Hlth, Montreal, PQ, Canada
[7] McGill Univ, Lady Davis Inst, Jewish Gen Hosp, Montreal, PQ, Canada
关键词
COVID-19; Long-COVID-19; Host; TLR7; RNAseq; Transcriptomics; Epigenomics; n; -Counter; DNA methylation; PACKAGE;
D O I
10.1016/j.envres.2022.114288
中图分类号
X [环境科学、安全科学];
学科分类号
08 ; 0830 ;
摘要
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 plat-forms, 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.
引用
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页数:7
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