Exploration of the shared gene signatures and comorbidity mechanisms of primary aldosteronism and atrial fibrillation

Q: What is the clinical evidence from this study?

Study design: Case-Control. Population: Primary aldosteronism and atrial fibrillation (n=60). Intervention: Primary aldosteronism complicated with atrial fibrillation (peripheral blood TNFSF10 mRNA expression) vs. Age- and sex-matched healthy controls. Primary outcome: Diagnostic discriminatory ability (AUC) and differential peripheral blood mRNA expression of hub gene TNFSF10 in PA patients with AF vs healthy controls (AUC 0.800, 95% CI 0.637-0.963, p=0.005).

Q: What does this research mean for the field?

Peripheral blood TNFSF10 mRNA expression is significantly decreased in patients with primary aldosteronism complicated by atrial fibrillation and serves as a potential biomarker for this comorbidity. Novelty: ClaimNovelty.NOVEL_FINDING. Consensus alignment: ConsensusAlignment.NEUTRAL.

Jindong Wan; Sen Liu; T. Luo; Yi Yang; Dan Wang; Xinquan Wang; Peng Zhou; Jixin Hou

doi:10.1530/ec-24-0402

October 30, 2024Endocrine ConnectionsOpen Access

Exploration of the shared gene signatures and comorbidity mechanisms of primary aldosteronism and atrial fibrillation

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Why the study?

Although evidence indicates a heightened incidence of atrial fibrillation in patients with primary aldosteronism, the underlying molecular mechanisms remain unclear.

Does peripheral blood expression of the shared hub gene TNFSF10 differentiate patients with primary aldosteronism complicated with atrial fibrillation from healthy controls?

Key Points

To investigate the shared molecular networks, biological pathways, and candidate hub genes underlying the comorbidity of primary aldosteronism and atrial fibrillation.
Extracted microarray datasets from the Gene Expression Omnibus database (GSE8514 and GSE79768) to identify overlapping differentially expressed genes through Gene Ontology, KEGG pathway, and protein-protein interaction network analyses.
Validated candidate hub genes using two external datasets (GSE60042 for primary aldosteronism and GSE41177 for atrial fibrillation).
Performed quantitative real-time polymerase chain reaction to measure hub gene expression in peripheral blood samples from 60 participants divided into four matched groups (n = 15 each: primary aldosteronism, atrial fibrillation, primary aldosteronism with atrial fibrillation, and healthy controls).
Analysis identified 33 common differentially expressed genes enriched in leukocyte migration, focal adhesion, and cytokine-cytokine receptor interactions, highlighting 13 hub genes including TNFSF10.
Quantitative real-time polymerase chain reaction confirmed that TNFSF10 expression levels were significantly lower in patients with primary aldosteronism, atrial fibrillation, and primary aldosteronism with atrial fibrillation compared to healthy controls.
ROC curve analysis revealed an AUC for TNFSF10 of 0.742 (95% CI: 0.563–0.922; P = 0.024) in primary aldosteronism, 0.778 (95% CI: 0.606–0.950; P = 0.010) in atrial fibrillation, and 0.800 (95% CI: 0.637–0.963; P = 0.005) in primary aldosteronism with atrial fibrillation.

Study Design

Type

Case-Control (n=60)

Multicenter

No

Structured PICO

Does peripheral blood expression of the shared hub gene TNFSF10 differentiate patients with primary aldosteronism complicated with atrial fibrillation from healthy controls?

P

Population

60 clinical participants (mean age ~56 years, 56.7% female) in four age- and sex-matched groups (PA, AF, PA with AF, and healthy controls) recruited from a single center in China, alongside four public GEO transcriptomic datasets.

E

Exposure

Bioinformatics identification (GO, KEGG, STRING PPI network, cytoHubba, GeneMANIA, TRRUST) and peripheral blood qPCR validation of shared hub gene expression (specifically TNFSF10) in patients with PA, AF, and PA complicated with AF

C

Comparator

Healthy controls matched for age and sex (n=15 in clinical cohort) and normal adrenal cortex / normal sinus rhythm tissue samples (in GEO datasets)

O

Outcome

Shared differentially expressed hub genes (specifically peripheral blood mRNA expression levels of TNFSF10) and diagnostic discriminatory performance (ROC AUC) for distinguishing PA, AF, and PA with AF from healthy controlssurrogate

Main Result

Effect estimate: AUC 0.800 (95% CI 0.637-0.963)

p-value: p=0.005

Limitations

Limited clinical information (such as age, sex, medication, and comorbidities) available in public transcriptomic databases and potential bias from contaminated tissues
Small sample sizes in both the pooled bioinformatics datasets and the clinical validation cohort
Reliance on publicly available RNA sequencing/microarray data from diverse populations introducing residual and uncontrolled confounding factors
Study is confined to transcriptomic analysis without further mechanistic validation through basic research
Limited clinical information in public databases (lacking data on age, sex, medication, and comorbidities) and potential bias from contaminated tissues
Small number of available samples in both the public GEO datasets and clinical cohorts
Potential residual and uncontrolled confounding factors due to reliance on publicly available transcriptomic data from diverse populations
Confined to transcriptomic analysis without further mechanistic validation through basic research

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Implication

Identifies downregulated TNFSF10 and shared immune/inflammatory pathways as a potential diagnostic biomarker and molecular link in patients with primary aldosteronism complicated by atrial fibrillation.

Abstract

Background: Primary aldosteronism (PA) is a prevalent cause of endocrine hypertension characterized by an excess of aldosterone that can induce proinflammatory, prooxidant and profibrotic effects on the heart. Emerging evidence indicates a heightened incidence of atrial fibrillation (AF) in patients with PA, suggesting a significant association between the two conditions. However, the underlying mechanisms remain unclear. The purpose of this study was to investigate the molecular networks associated with the development of both PA and AF. Methods: Datasets were obtained from the Gene Expression Omnibus database. Hub genes were identified by enrichment and protein-protein interaction analysis. These hub genes were subsequently validated via two independent external datasets: GSE60042 (PA microarray dataset) and GSE41177 (AF microarray dataset). Following the identification of shared genes, quantitative real-time polymerase chain reaction (qPCR) was employed to verify the reliability of the dataset and to further confirm the presence of shared genes in clinical samples. Results: The results of the common gene analysis revealed that immune and inflammatory responses may be shared features in the pathophysiology of PA and AF. One hub gene, specifically tumor necrosis factor superfamily member 10 (TNFSF10), was identified through various analyses and subsequently validated via qPCR. Compared with that in healthy controls, the expression level of TNFSF10 was lower in PA patients with AF. Conclusion: Our findings indicate that TNFSF10 may play a role in the pathophysiology of AF complications associated with PA conditions, suggesting that it could serve as a potential target for the diagnosis or treatment of PA patients complicated with AF.

Discussion

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Cite This Study

Wan et al. (2024) conducted a case-control in Primary aldosteronism and atrial fibrillation (n=60). Primary aldosteronism complicated with atrial fibrillation (peripheral blood TNFSF10 mRNA expression) vs. Age- and sex-matched healthy controls was evaluated on Diagnostic discriminatory ability (AUC) and differential peripheral blood mRNA expression of hub gene TNFSF10 in PA patients with AF vs healthy controls (AUC 0.800, 95% CI 0.637-0.963, p=0.005).

synapsesocial.com/papers/6a7efeb8ad7bbf6c1bd0a98b https://doi.org/10.1530/ec-24-0402

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Exploration of the shared gene signatures and comorbidity mechanisms of primary aldosteronism and atrial fibrillation

Figures

Key Points

Study Design

Structured PICO

Main Result

Limitations

Ask about this paper

Implication

Abstract

Discussion

Cite This Study

Exploration of the shared gene signatures and comorbidity mechanisms of primary aldosteronism and atrial fibrillation

Figures

Key Points

Study Design

Structured PICO

Main Result

Limitations

Ask about this paper

Implication

Abstract

Discussion

Cite This Study

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