# Optimizing C-Type Natriuretic Peptide and Receptor Expression Analysis with Droplet Digital™ PCR: Advancing Biomarker Discovery for Brugada Syndrome?

**Authors:** Manuela Cabiati, Federico Vozzi, Elisa Persiani, Marcello Piacenti, Andrea Rossi, Agnese Sgalippa, Antonella Cecchettini, Gianluca Solarino, Giulio Zucchelli, Lorenzo Mazzocchetti, Pasquale Notarstefano, Letizia Guiducci, Maria Aurora Morales, Silvia Del Ry

PMC · DOI: 10.3390/biom15060792 · Biomolecules · 2025-05-29

## TL;DR

This study uses a sensitive PCR method to analyze CNP and its receptors in Brugada syndrome patients, finding reduced receptor expression and correlations with body weight and height.

## Contribution

First study to use ddPCR to analyze CNP and its receptors in Brugada syndrome, revealing their expression patterns.

## Key findings

- NPR-B and NPR-C expression was significantly reduced in Brugada syndrome patients.
- Strong correlations were observed between CNP and its receptors, as well as between the receptors themselves.
- Body weight and height correlated with CNP and receptor expression levels.

## Abstract

Brugada syndrome (BrS) is a cardiac disease associated with characteristic ECG abnormalities and a heightened risk of sudden cardiac death, especially in young individuals with structurally normal hearts. The primary aim of this study was to highlight, for the first time, the potential of using droplet digital PCR (ddPCR), a highly sensitive method, to detect C-type natriuretic peptide (CNP) and its receptors, NPR-B and NPR-C, expression in BrS. Whole-blood samples from 12 subjects with type 1 BrS and 12 controls were analyzed. CNP expression was detectable and lower in BrS patients than in the controls, although not significantly. NPR-B and NPR-C expression was significantly reduced in the same patients (p ≤ 0.05). Strong correlations were observed between CNP and NPR-B (p = 0.01) and NPR-C (p < 0.0001), as well as between NPR-B and NPR-C (p = 0.0002). Body weight correlated with CNP (p = 0.02), NPR-B (p = 0.03), and NPR-C (p = 0.02); meanwhile, NPR-B expression was related to height (p = 0.05). This study is the first to analyze CNP expression and its specific receptors using ddPCR technology, showing for the first time their presence and activation in individuals with BrS. Although further research is needed to clarify CNP-related mechanisms, these findings offer a valuable starting point for exploring its role in BrS.

## Linked entities

- **Proteins:** NPR2 (natriuretic peptide receptor 2), NPR3 (natriuretic peptide receptor 3)
- **Diseases:** Brugada syndrome (MONDO:0015263)

## Full-text entities

- **Genes:** NPR3 (natriuretic peptide receptor 3) [NCBI Gene 4883] {aka ANP-C, ANPR-C, ANPRC, BOMOS, C5orf23, GUCY2B}, NPR2 (natriuretic peptide receptor 2) [NCBI Gene 4882] {aka AMDM, ANPRB, ANPb, ECDM, GC-B, GCB}, NPPC (natriuretic peptide C) [NCBI Gene 4880] {aka CNP, CNP2}
- **Diseases:** cardiac disease (MESH:D006331), sudden cardiac death (MESH:D016757), BrS (MESH:D053840)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Full text

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## Figures

6 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12190965/full.md

## References

42 references — full list in the complete paper: https://tomesphere.com/paper/PMC12190965/full.md

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Source: https://tomesphere.com/paper/PMC12190965