Abstract | AIMS:
Brugada syndrome is an inherited sudden-death arrhythmia syndrome. Na(+)-current dysfunction is central, but mutations in the SCN5A gene (encoding the cardiac Na(+)-channel Nav1.5) are present in only 20% of probands. This study addressed the possibility that Brugada patients display specific expression patterns for ion-channels regulating cardiac conduction, excitability, and repolarization. METHODS AND RESULTS: Transcriptional profiling was performed on right-ventricular endomyocardial biopsies from 10 unrelated Brugada probands, 11 non-diseased organ-donors, seven heart-transplant recipients, 10 with arrhythmogenic right-ventricular cardiomyopathy, and nine with idiopathic right-ventricular outflow-tract tachycardia. Brugada patients showed distinct clustering differences vs. the two control and two other ventricular-tachyarrhythmia groups, including 14 of 77 genes encoding important ion-channel/ion-transporter subunits. Nav1.5 and K(+)-channels Kv4.3 and Kir3.4 were more weakly expressed, whereas the Na(+)-channel Nav2.1 and the K(+)-channel TWIK1 were more strongly expressed, in Brugada syndrome. Differences were also seen in Ca(2+)-homeostasis transcripts, including stronger expression of RYR2 and NCX1. The molecular profile of Brugada patients with SCN5A mutations did not differ from Brugada patients without SCN5A mutations. CONCLUSION: Brugada patients exhibit a common ion-channel molecular expression signature, irrespective of the culprit gene. This finding has potentially important implications for our understanding of the pathophysiology of Brugada syndrome, with possible therapeutic and diagnostic consequences.
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Authors | Nathalie Gaborit, Thomas Wichter, Andras Varro, Viktoria Szuts, Guillaume Lamirault, Lars Eckardt, Matthias Paul, Günter Breithardt, Eric Schulze-Bahr, Denis Escande, Stanley Nattel, Sophie Demolombe |
Journal | European heart journal
(Eur Heart J)
Vol. 30
Issue 4
Pg. 487-96
(Feb 2009)
ISSN: 1522-9645 [Electronic] England |
PMID | 19029124
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Ion Channels
- Muscle Proteins
- NAV1.5 Voltage-Gated Sodium Channel
- SCN5A protein, human
- Sodium Channels
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Topics |
- Adult
- Arrhythmogenic Right Ventricular Dysplasia
(genetics, physiopathology)
- Brugada Syndrome
(diagnosis, genetics, physiopathology)
- Female
- Gene Expression
- Gene Expression Profiling
(methods)
- Genotype
- Heart Ventricles
(metabolism, physiopathology)
- Humans
- Ion Channels
(genetics)
- Male
- Middle Aged
- Muscle Proteins
(genetics)
- Mutation
(genetics)
- NAV1.5 Voltage-Gated Sodium Channel
- Phenotype
- Sodium Channels
(genetics)
- Tachycardia, Ventricular
(genetics, physiopathology)
- Transcription, Genetic
(genetics)
- Young Adult
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