MRNA Expression Profiles and Molecular Biomarkers Involved in Inflammatory Response for Essential Hypertension in Kazakh Population From Xinjiang

Abstract

Abstract Background To identify hypertensive inflammation-related mRNA in peripheral blood mononuclear cells (PBMCs) from patients with essential hypertension (EH) of Kazakh Chinese population in Xinjiang, and offer theoretical foundation for further understanding the immune mechanisms that contribute to EH in Kazakh and provide specific molecular biomarkers for clinical diagnosis and targeted-specific treatments of this disorder. Methods Thirty Kazakh patients with EH and 30 age-matched healthy Kazakh people were divided into EH group and control group. After performing blood pressure measurement and determination of serum lipids and blood glucose, total RNA was isolated from PBMCs of hypertensive Kazakh patients and healthy Kazakh subjects, and differentially expressed mRNA in 6 randomly selected samples from each group were identified with human lncRNA/mRNA V4.0 microarray. Gene set enrichment analysis (GSEA), disease process, the Gene Ontology (GO), and Kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment analysis of differentially expressed mRNA were carried out using R language and ClusterProfiler software package. Reverse transcription quantitative real-time PCR (qRT-PCR) was used to validate the differential expression pattern of inflammation-related genes in the mRNA microarray data and results of bioinformatics analysis. Results The average blood pressure was significantly higher in the EH group than those in the control group (P < 0.01), while there was no statistical significance for the levels of serum lipids and blood glucose between the 2 groups. Compared with healthy Kazakh controls, a total of 522 mRNA were significantly differentially expressed from PBMCs of hypertensive Kazakh patients with fold change of ≥1.5 and P value <5% in expression. Among them, 411 were upregulated and 111 were downregulated. GO enrichment analysis of upregulated mRNA identified numerous inflammation-related biological processes and molecular functions. Many of these processes and molecular function were mainly involved in immune response-regulating signaling pathway, immune response-activating signal transduction, antigen binding, immunoglobulin receptor binding and peptide antigen binding, etc. GSEA and KEGG pathway analysis for the upregulated mRNA indicated several positively enriched gene sets and pathways related to inflammatory response, such as focal adhesion, cell adhesion molecules, chemokine signaling pathway, leukocyte transendothelial migration, cytokine–cytokine receptor interaction, and B-cell receptor signaling pathway. qRT-PCR validation results of 14 mRNA related to inflammatory response were consistent with the microarray data. Conclusions This is the first study to identify gene expression profile involved in hypertensive inflammation in Kazakh Chinese population in Xinjiang with EH, and not only provides specific molecular biomarkers for predicting and diagnosing progression of EH, but also will provide targeted-specific treatments of this disorder in Kazakh Chinese population in Xinjiang.