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COVID-19 患者的全基因组 DNA 甲基化研究。

An epigenome-wide DNA methylation study of patients with COVID-19.

机构信息

Department of Respiratory and Critical Care Medicine, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China.

Clinical Nursing Department, School of Nursing, Cheeloo College of Medicine, Shandong University, Jinan, China.

出版信息

Ann Hum Genet. 2021 Nov;85(6):221-234. doi: 10.1111/ahg.12440. Epub 2021 Jun 29.

Abstract

In the early 2000s, emerging SARS-CoV-2, which is highly pathogenic, posed a great threat to public health. During COVID-19, epigenetic regulation is deemed to be an important part of the pathophysiology and illness severity. Using the Illumina Infinium Methylation EPIC BeadChip (850 K), we investigated genome-wide differences in DNA methylation between healthy subjects and COVID-19 patients with different disease severities. We conducted a combined analysis and selected 35 "marker" genes that could indicate a SARS-CoV-2 infection, including 12 (ATHL1, CHN2, CHST15, CPLX2, CRHR2, DCAKD, GNAI2, HECW1, HYAL1, MIR510, PDE11A, and SMG6) situated in the promoter region. The functions and pathways of differentially methylated genes were enriched in biological processes, signal transduction, and the immune system. In the "Severe versus Mild" group, differentially methylated genes, after eliminating duplicates, were used for PPI analyses. The four hub genes (GNG7, GNAS, PRKCZ, and PRKAG2) that had the highest degree of nodes were identified and among them, GNG7 and GNAS genes expressions were also downregulated in the severe group in sequencing results. Above all, the results suggest that GNG7 and GNAS may play a non-ignorable role in the progression of COVID-19. In conclusion, the identified key genes and related pathways in the current study can be used to study the molecular mechanisms of COVID-19 and may provide possibilities for specific treatments.

摘要

在 21 世纪初,高致病性的新兴 SARS-CoV-2 对公共卫生构成了巨大威胁。在 COVID-19 期间,表观遗传调控被认为是病理生理学和疾病严重程度的重要组成部分。我们使用 Illumina Infinium Methylation EPIC BeadChip(850 K),研究了健康受试者和不同疾病严重程度 COVID-19 患者之间全基因组 DNA 甲基化差异。我们进行了联合分析,并选择了 35 个“标记”基因,这些基因可以指示 SARS-CoV-2 感染,包括 12 个(ATHL1、CHN2、CHST15、CPLX2、CRHR2、DCAKD、GNAI2、HECW1、HYAL1、MIR510、PDE11A 和 SMG6)位于启动子区域。差异甲基化基因的功能和途径在生物学过程、信号转导和免疫系统中富集。在“严重与轻度”组中,消除重复后,使用差异甲基化基因进行 PPI 分析。鉴定出具有最高节点度的四个枢纽基因(GNG7、GNAS、PRKCZ 和 PRKAG2),其中 GNG7 和 GNAS 基因在测序结果中在严重组中也下调表达。综上所述,结果表明 GNG7 和 GNAS 可能在 COVID-19 的进展中发挥不可忽视的作用。总之,本研究中鉴定的关键基因和相关途径可用于研究 COVID-19 的分子机制,并为特定治疗提供可能性。

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