高血压患者白细胞免疫调控基因的表达模式及作用机制研究

Study on expression patterns and regulation mechanism of immune regulation related genes in white blood cells of patients with hypertension

目的:采用生物信息学方法筛选人类免疫调控相关基因在高血压患者白细胞中的表达模式及调控作用,为高血压的预防和治疗提供参考依据。方法:基于公共数据集GSE74144,对数据预处理后筛选差异表达基因(DEGs,Log2|Fold Change|>1.3,FDR<0.05),获取高血压患者白细胞差异表达免疫调控基因,对上述基因行GO和KEGG富集分析,建立蛋白互作(PPI)网络等,并采用受试者工作曲线分析上述基因对高血压的鉴别意义。结果:与健康对照组相比,高血压患者白细胞共有73个DEGs,主要参与囊泡和免疫系统相关的生物学功能;随后获得16个高血压患者差异表达的免疫调控相关基因,其中10个基因在高血压患者白细胞中表达上调(62.50%),6个基因表达下调(37.50%),主要参与细胞表面受体信号通路、免疫系统过程、外部刺激反应、IFN-γ反应及B细胞受体调节等生物学过程或信号通路;HLA-B蛋白是PPI网络的关键蛋白;与CD19、BICC1具有调控关系的miRNAs最多,与FERMT3具有调控关系的转录因子最多;高血压患者免疫相关基因会受多种环境化学物影响。结论:高血压患者机体长期处于微炎症状态,患者的免疫系统处于一定程度的激活状态,本研究发现的一系列分子标志物有助于了解高血压患者的免疫状态,可为预防和治疗该病提供新的思路和靶点。

Objective:To screen expression patterns and regulatory mechanism of human immune regulation-related genes in white blood cells of patients with hypertension by bioinformatics method,so as to provide a reference for prevention and treatment of hypertension.Methods:Based on the public dataset GSE74144,after data preprocessing,differentially expressed genes(DEGs,Log 2|Fold Change|>1.3,FDR<0.05)were screened to obtain the lists of differentially expressed genes related to immunity of white blood cells in patients with hypertension.GO and KEGG enrichment analysis were performed on the above genes,and protein-protein interaction(PPI)network etc.were established,and then receiver operating curve was used to analyze significance of the above genes in identification of hypertension.Results:Compared with healthy control group,there were 73 DEGs in leukocytes of hypertensive patients,which were mainly involved in biological functions of vesicles and immune system.Subsequently,16 immunoregulatory-related genes differentially expressed in hypertensive patients were obtained,among them,10 genes were up-regulated(62.50%)and 6 genes were down-regulated(37.50%)in leukocytes of hypertensive patients,which were mainly involved in biological processes such as cell surface receptor signaling pathways,immune system processes,external stimulus responses,IFN-γresponses and B cell receptor regulation or signaling pathway;HLA-B protein was the key protein of PPI network;CD19 and BICC1 had the most miRNAs that have a regulatory relationship,and the transcription factors that showed regulatory relationships with FERMT3 were the most;immune-related genes in hypertensive patients were also affected by a variety of environmental chemicals.Conclusion:Body of patients with hyperten‐sion is in a state of micro-inflammation for a long time,and the patient's immune system is in a certain degree of activation.The series of molecular markers discovered in this study are helpful to understand the immune status of patients with hypertension,and can be used to prevent and treat the disease,provide new ideas and targets.