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A Transcriptomic Analysis of Smoking-Induced Gene Expression Alterations in Coronary Artery Disease Patients
Mohammed Merzah1, Szilárd Póliska2, László Balogh3
1Department of Public Health and Epidemiology, Faculty of Medicine, University of Debrecen, H-4032 Debrecen, Hungary.
Insights
Smoking significantly alters blood gene expression in coronary artery disease (CAD) patients. This study identified key genes, including RCAN3, TRAV4, and JCHAIN, implicated in CAD development among smokers.
Area of Science:
- Cardiovascular Genetics
- Molecular Biology
- Genomics
Background:
- Smoking is a known risk factor for coronary artery disease (CAD).
- Limited research exists on smoking's impact on blood gene expression in CAD patients.
- A gap in understanding molecular mechanisms linking smoking and CAD necessitates further investigation.
Purpose of the Study:
- To investigate the effects of smoking on blood gene expression in patients with coronary artery disease (CAD).
- To identify differentially expressed genes (DEGs) associated with smoking status in CAD.
- To explore potential molecular pathways influenced by smoking in CAD pathogenesis.
Main Methods:
- Single-center, cross-sectional study design with strict inclusion criteria.
- High-throughput next-generation sequencing (NGS) with single-end sequencing (75-cycle read length).
- Analysis of gene expression differences between smokers and non-smokers in 44 CAD patients.
Main Results:
- Identified 120 differentially expressed genes (DEGs) between smokers and non-smokers (FC ≥ 1.5, p < 0.05).
- 31 statistically significant DEGs (FC ≥ 2.0, FDR ≤ 0.03) were found, including 5 upregulated (immune response) and 26 downregulated (oxygen/heme binding).
- Overexpression of RCAN3, TRAV4, and JCHAIN genes noted in smokers, suggesting novel roles in CAD.
Conclusions:
- Smoking induces significant changes in blood gene expression in CAD patients.
- Identified DEGs provide molecular insights into CAD pathogenesis related to smoking.
- RCAN3, TRAV4, and JCHAIN represent potential novel biomarkers or therapeutic targets in smoking-related CAD.
Abstract:
Smoking is a well established risk factor for coronary artery disease (CAD). Despite this, there have been no previous studies investigating the effects of smoking on blood gene expression in CAD patients. This single-centre cross-sectional study was designed with clearly defined inclusion criteria to address this gap. We conducted a high-throughput approach using next generation sequencing analysis with a single-end sequencing protocol and a read length of 75-cycles. Sixty-one patients with a median age of 67 years (range: 28-88 years) were recruited, and only 44 subjects were included for further analyses. Our investigation revealed 120 differentially expressed genes (DEGs) between smokers and nonsmokers, with a fold change (FC) of ≥1.5 and a p-value < 0.05. Among these DEGs, 15 were upregulated and 105 were downregulated. Notably, when applying a more stringent adjusted FC ≥ 2.0, 31 DEGs (5 upregulated, annotated to immune response pathways, and 26 downregulated, involving oxygen and haem binding or activity, with FDR ≤ 0.03) remained statistically significant at an alpha level of <0.05. Our results illuminate the molecular mechanisms underlying CAD, fortifying existing epidemiological evidence. Of particular interest is the unexplored overexpression of RCAN3, TRAV4, and JCHAIN genes, which may hold promising implications for the involvement of these genes in CAD among smokers.
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