GENYO. Center for Genomics and Oncological Research Pfizer/University of Granada/Andalusian Regional Government, Granada, Spain.
Servicio de Microbiología e Inmunología, Hospital Clínico Universitario de Valladolid, Valladolid, Spain.
Nat Commun. 2022 Aug 6;13(1):4597. doi: 10.1038/s41467-022-32357-2.
SARS-CoV-2 infection can cause an inflammatory syndrome (COVID-19) leading, in many cases, to bilateral pneumonia, severe dyspnea, and in ~5% of these, death. DNA methylation is known to play an important role in the regulation of the immune processes behind COVID-19 progression, however it has not been studied in depth. In this study, we aim to evaluate the implication of DNA methylation in COVID-19 progression by means of a genome-wide DNA methylation analysis combined with DNA genotyping. The results reveal the existence of epigenomic regulation of functional pathways associated with COVID-19 progression and mediated by genetic loci. We find an environmental trait-related signature that discriminates mild from severe cases and regulates, among other cytokines, IL-6 expression via the transcription factor CEBP. The analyses suggest that an interaction between environmental contribution, genetics, and epigenetics might be playing a role in triggering the cytokine storm described in the most severe cases.
SARS-CoV-2 感染可引起炎症综合征（COVID-19），在许多情况下导致双侧肺炎、严重呼吸困难，而在这些患者中约有 5%死亡。DNA 甲基化在 COVID-19 进展背后的免疫过程调控中起着重要作用，但尚未得到深入研究。在这项研究中，我们旨在通过全基因组 DNA 甲基化分析结合 DNA 基因分型，评估 DNA 甲基化在 COVID-19 进展中的作用。研究结果揭示了与 COVID-19 进展相关的功能途径的表观基因组调控的存在，这些途径是由遗传基因座介导的。我们发现了一个与环境特征相关的特征，可以区分轻症和重症病例，并通过转录因子 CEBP 调节其他细胞因子中的 IL-6 表达。这些分析表明，环境因素、遗传因素和表观遗传因素之间的相互作用可能在引发最严重病例中描述的细胞因子风暴中发挥作用。
