李晶 张荣强 张灵芝 戚燕 郝洁 何傲月 赵旭 李秀芹

摘要：目的 探讨硒蛋白基因在新型冠状病毒感染（COVID-19）患者中的表达水平及其可能的调控机制。方法 从基因表达综合数据库获取数据集GSE177477，样本由有症状组（n=11）、无症状组（n=18）和健康对照组（n=18）构成。对数据集进行预处理，筛选出与COVID-19相关的差异表达基因，并进行基因本体功能注释和京都基因与基因组百科全书富集分析，建立差异表达硒蛋白基因的蛋白质-蛋白质相互作用网络，采用多因素Logistic回归分析硒蛋白基因对COVID-19患者是否出现症状的影响。结果 与健康对照组比较，有症状的COVID-19患者中GPX1、GPX4、GPX6、DIO2、TXNRD1、SELENOF、SELENOK、SELENOS、SELENOT、SELENOW基因表达均升高，TXNRD2、SELENON基因表达均下降（P均＜0.05）；无症状的COVID-19患者中GPX2、SELENOI、SELENOO、SELENOS、SELENOT、SELENOW基因表达均升高，SELP基因表达下降（P均＜0.05）。多因素Logistic回归分析结果显示，GPX1（OR=0.067，95%CI=0.005～0.904，P=0.042）、SELENON（OR=56.663，95%CI=3.114～856.999，P=0.006）基因的异常高表达是有症状COVID-19患者的影响因素，SELP基因的异常高表达是无症状COVID-19患者的危险因素（OR=15.000，95%CI=2.537～88.70 P=0.003）。结论 硒蛋白基因的差异表达参与调控COVID-19疾病的发生发展，为COVID-19的预防和治疗提供新的参考依据。

关键词：新型冠状病毒感染；硒蛋白；表达及调控；Logistic回归

中图分类号： R183.3  文献标识码： A  文章编号：1000-503X（2024）03-0316-08

DOI：10.3881/j.issn.1000-503X.15834

Expression Levels and Regulation of Selenoprotein Genes in Patients With Coronavirus Disease 2019

LI Jing ZHANG Rongqiang ZHANG Lingzhi2，QI Yan HAO Jie HE Aoyue ZHAO Xu LI Xiuqin3

1Department of Epidemiology and Health Statistics，School of Public Health，Shaanxi University of Chinese Medicine，Xianyang，Shaanxi 712046，China

2Department of Laboratory Medicine，The Second Hospital of Hanbin District，Ankang，Shaanxi 72502 China

3Department of Public Administration，School of Humanities and Management，Shaanxi University of Chinese Medicine，Xianyang，Shaanxi 712046，China

Corresponding author：LI Xiuqin Tel：029-38185218，E-mail：lixiuqin2000@163.com

ABSTRACT：Objective To investigate the expression levels of selenoprotein genes in the patients with coronavirus disease 2019 （COVID-19） and the possible regulatory mechanisms.Methods The dataset GSE177477 was obtained from the Gene Expression Omnibus，consisting of a symptomatic group （n=11），an asymptomatic group （n=18），and a healthy control group （n=18）.The dataset was preprocessed to screen the differentially expressed genes （DEG） related to COVID-19，and gene ontology functional annotation and Kyoto encyclopedia of genes and genomes enrichment analysis were performed for the DEGs.The protein-protein interaction network of DEGs was established，and multivariate Logistic regression was employed to analyze the effects of selenoprotein genes on the presence/absence of symptoms in the patients with COVID-19.Results Compared with the healthy control，the symptomatic COVID-19 patients presented up-regulated expression of GPX GPX4，GPX6，DIO2，TXNRD SELENOF，SELENOK，SELENOS，SELENOT，and SELENOW and down-regulated expression of TXNRD2 and SELENON （all P<0.05）.The asymptomatic patients showcased up-regulated expression of GPX2，SELENOI，SELENOO，SELENOS，SELENOT，and SELENOW and down-regulated expression of SELP （all P<0.05）.The results of multivariate Logistic regression analysis showed that the abnormally high expression of GPX1 （OR=0.067，95%CI=0.005-0.904，P=0.042） and SELENON （OR=56.663，95%CI=3.114-856.999，P=0.006） was the risk factor for symptomatic COVID-19，and the abnormally high expression of SELP was a risk factor for asymptomatic COVID-19 （OR=15.000，95%CI=2.537-88.70 P=0.003）.Conclusions Selenoprotein genes with differential expression are involved in the regulation of COVID-19 development.The findings provide a new reference for the prevention and treatment of COVID-19.

Key words：coronavirus disease 2019；selenoprotein；expression and regulation；Logistic regression

Acta Acad Med Sin，2024，46（3）：316-323

新型冠状病毒感染（coronavirus disease 2019，COVID-19）是由严重急性呼吸综合征冠状病毒2（SARS-CoV-2）引起的一种传染病，可通过呼吸道飞沫和气溶胶途径传播，人群普遍易感，传播速度较快。2023年1月7日我国发布的《新型冠状病毒感染防控方案（第十版）》将COVID-19纳入按乙类管控的乙类传染病［1］。硒是人体所必需的一种微量元素，在体内主要以硒蛋白的形式发挥生物学作用。研究证实，硒蛋白与病毒感染之间存在一定的联系，其作用机制复杂，涉及宿主细胞和病毒本身硒蛋白的表达与功能、机体的免疫应答、氧化还原平衡及各种因素之间的交互作用［2］。……