原发性高血压患者血浆基因表达谱的生物信息学分析

Bioinformatics analysis on gene expression profile in plasma of hypertensives

目的应用生物信息学方法分析原发性高血压(EH)患者与正常血压成人差异表达的长链非编码RNA(lncRNA)和信使RNA(mRNA),从分子水平探讨EH的发病机制,为研究EH提供新思路。方法从美国国立生物技术信息中心公共数据平台下载包含5份EH患者和5份正常血压者(对照组)的血浆样本基因芯片数据集GSE76845(为了降低个体差异,每三个人的血浆混合为一份样本),使用R语言包寻找差异基因,进行基因集合富集分析(GSEA),使用miRcode、miRDB、miRTarBase和TargetScan数据库预测靶向微小RNA(miRNA)和mRNA并构建内源竞争RNA(ceRNA)调控网络。结果与对照组比较,EH组共筛选出191个差异lncRNA(90个上调、101个下调)和1187个差异mRNA(533个上调、654个下调),GSEA分析得到泛醌和其他萜烯类醌的生物合成,甲状旁腺激素的合成、分泌及作用,脂肪酸代谢和甾体激素生物合成等17条通路可能参与高血压的发生。构建了包含150个节点和488个交互对的ceRNA网络。结论采用生物信息学方法分析EH,为EH发生发展的分子机制和治疗靶点研究提供了研究方向和理论依据。

Objective The differential expression of long noncoding RNA(lncRNA)and messenger RNA(mRNA)between patients with essential hypertension(EH)and normotensive adults was analyzed by bioinformatics.To explore the pathogenesis of EH at the molecular level and provide new ideas for the study of EH.Methods The gene chip dataset GSE76845,which contained 5 plasma samples from patients with EH and 5 normotensives,was downloaded from the National Biotechnology Information Center Public Data Platform(in order to reduce individual differences,the plasma of each three people was mixed into one sample).R language package was used to identify differently expressed genes.And gene set enrichment analysis(GSEA)was performed.The target microRNA(miRNA)and mRNA were predicted by microcode,microDB,microTarBase and TargetScan databases.Then a competing endogenous RNAs(ceRNA)regulatory network was constructed.Results Compared with the healthy control group,191 differential lncRNAs(90 up-regulated and 101 down-regulated)and 1187 differential mRNAs(533 up-regulated and 654 down-regulated)were screened in EH group.GSEA analysis showed that 17 pathways,including ubiquinone and other terpenoid-quinone biosynthesis,parathyroid hormone synthesis secretion and action,fatty acid metabolism and steroid hormone biosynthesis,may be involved in the occurrence of hypertension.A ceRNA network consisting of 150 nodes and 488 interactive pairs was constructed.Conclusion Bioinformatics method can provide research direction and theoretical basis for the molecular mechanism of EH occurrence and development and for its therapeutic target.