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Quantitative Real-Time Analysis of Differentially Expressed Genes in Peripheral Blood Samples of Hypertension
Fawad Ali1,2, Arifullah Khan1, Syed Aun Muhammad3
1Riphah Institute of Pharmaceutical Sciences, Riphah International University, Islamabad 44000, Pakistan.
Insights
This study identified seven key genes linked to hypertension, revealing how their altered expression contributes to cardiovascular issues and disease. Findings may guide new hypertension treatment strategies.
Area of Science:
- Genomics and Molecular Biology
- Cardiovascular Research
- Systems Biology
Background:
- Hypertension (HTN) is a major global risk factor for cardiovascular disease, stroke, and mortality.
- Understanding the genetic underpinnings of HTN is crucial for developing effective treatments.
Purpose of the Study:
- To identify differentially expressed genes (DEGs) involved in the pathophysiology of hypertension.
- To analyze the biological functions and regulatory mechanisms of these DEGs.
Main Methods:
- Utilized a system-level framework to analyze 22 public cDNA Affymetrix datasets for HTN.
- Performed Gene Ontology (GO) and pathway enrichment analyses.
- Validated gene expression profiles using quantitative polymerase chain reaction (qPCR).
Main Results:
- Identified seven significant hypertension-related genes: ADM, ANGPTL4, USP8, EDN1, NFIL3, MSR1, and CEBPD.
- Discovered enriched pathways related to HIF-1-α transcription, endothelin, and GPCR-binding ligands.
- Observed significant upregulation of ADM, ANGPTL4, USP8, and EDN1, and downregulation of CEBPD, MSR1, and NFIL3.
Conclusions:
- Aberrant expression of identified DEGs is associated with hypertension development and cardiovascular abnormalities.
- These findings offer insights into potential therapeutic targets for modulating hypertension.
Abstract:
Hypertension (HTN) is considered one of the most important and well-established reasons for cardiovascular abnormalities, strokes, and premature mortality globally. This study was designed to explore possible differentially expressed genes (DEGs) that contribute to the pathophysiology of hypertension. To identify the DEGs of HTN, we investigated 22 publicly available cDNA Affymetrix datasets using an integrated system-level framework. Gene Ontology (GO), pathway enrichment, and transcriptional factors were analyzed to reveal biological information. From 50 DEGs, we ranked 7 hypertension-related genes (p-value < 0.05): ADM, ANGPTL4, USP8, EDN, NFIL3, MSR1, and CEBPD. The enriched terms revealed significant functional roles of HIF-1-α transcription; endothelin; GPCR-binding ligand; and signaling pathways of EGF, PIk3, and ARF6. SP1 (66.7%), KLF7 (33.3%), and STAT1 (16.7%) are transcriptional factors associated with the regulatory mechanism. The expression profiles of these DEGs as verified by qPCR showed 3-times higher fold changes (2-ΔΔCt) in ADM, ANGPTL4, USP8, and EDN1 genes compared to control, while CEBPD, MSR1 and NFIL3 were downregulated. The aberrant expression of these genes is associated with the pathophysiological development and cardiovascular abnormalities. This study will help to modulate the therapeutic strategies of hypertension.
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