Identification of key genes from the visceral adipose tissues of overweight/obese adults with hypertension through transcriptome sequencing

Abstract

Overweight and obese (OW/OB) adults are at increased risk of hypertension due to visceral adipose tissue (VAT) inflammation. In this study, we explored gene level differences in the VAT of hypertensive and normotensive OW/OB patients. VAT samples obtained from six OW/OB adults (three hypertensive, three normotensive) were subjected to transcriptome sequencing analysis. Gene set enrichment analysis was conducted for all gene expression data to identify differentially expressed genes (DEGs) with |log2 (fold change)| ≥ 1 and q < 0.05. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes functional enrichment analyses were performed on the DEGs and hub genes were identified by constructing a protein-protein interaction (PPI) network. The proposed hub genes were validated using quantitative real-time PCR in ten other samples from five hypertensive and five normotensive patients. In addition, we performed ROC analysis and spearman correlation analysis. A total of 84 DEGs were identified between VAT samples from OW/OB patients with and without hypertension, among which 21 were significantly up-regulated and 63 were significantly down-regulated. Bioinformatics analysis revealed that spleen function was related to hypertension in OW/OB adults. Meanwhile, PPI network analysis identified the following top 10 hub genes: CD79A, CR2, SELL, CD22, IL7R, CCR7, TNFRSF13C, CXCR4, POU2AF1, and JAK3. Through qPCR verification, we found that CXCR4, CD22 and IL7R were statistically significant. QPCR verification suggested that RELA were statistically significant. However, qPCR verification indicated that NF-KB1 and KLF2 were not statistically significant. These hub genes were mainly regulated by the transcription factors RELA. The AUC of ROC analysis for CXCR4, IL7R and CD22 was 0.92. What’s more, VAT CXCR4 and CD22 were positively related to RELA relative expression levels. Take together, our research demonstrates that CXCR4, IL7R and CD22 related to VAT in hypertensive OW/OB adults could serve as future therapeutic targets.