Genetic modulation of brugada syndrome by a common polymorphism

Eric Lizotte, M. Juhani Junttila, Marie Pierre Dube, Kui Hong, Begona Benito, Marc De Zutter, Stefan Henkens, Andrea Sarkozy, Heikki V. Huikuri, Jeffrey Towbin, Matteo Vatta, Pedro Brugada, Josep Brugada, Ramon Brugada

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Abstract

Genetic Modulation of Brugada Syndrome by a Common Polymorphism. Background: Brugada syndrome predisposes some subjects to ventricular tachyarrhythmias and sudden cardiac death. Mutations in SCN5A gene have been associated with ∼25% of Brugada syndrome patients. A common variant in SCN5A, H558R has shown to improve sodium channel activity in mutated channels. We studied whether common variant H558R has any clinical implications in the phenotype of Brugada syndrome. Methods: Our study population consisted of Brugada syndrome subjects 75 with SCN5A mutation and 92 without SCN5A mutation. Their mean age was 39 ± 15 and 42 ± 17 years, and 65% and 86% were male, respectively. We measured PR-, QRS-, QTc-intervals from leads II and V2 of the 12-lead ECG. We also evaluated J-point amplitude from lead V2 and R'/S ratio from lead aVR (the "aVR sign"). The H558R (A→G) genotype was detected with direct sequencing of the SCN5A gene. Results: The AA genotype carriers had longer QRS duration in lead II (P = 0.017) and higher J-point elevation in lead V2 (P = 0.013), higher "aVR sign" (P = 0.005) and a trend toward more subjects with symptoms (P = 0.067) than G allele carriers. None of the results were significant in Brugada syndrome subjects without SCN5A mutation. Conclusion: The common variant H558R seems to be a genetic modulator of Brugada syndrome among carriers of a SCN5A mutation, in whom the presence of the less common allele G improves the ECG characteristics and clinical phenotype. (J Cardiovasc Electrophysiol, Vol. pp. 1137-1141)

Original languageEnglish (US)
Pages (from-to)1137-1141
Number of pages5
JournalJournal of cardiovascular electrophysiology
Volume20
Issue number10
DOIs
StatePublished - Nov 3 2009

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Brugada Syndrome
Mutation
Electrocardiography
Alleles
Genotype
Phenotype
Sodium Channels
Sudden Cardiac Death
Tachycardia
Genes
Lead

All Science Journal Classification (ASJC) codes

  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

Cite this

Lizotte, E., Junttila, M. J., Dube, M. P., Hong, K., Benito, B., De Zutter, M., ... Brugada, R. (2009). Genetic modulation of brugada syndrome by a common polymorphism. Journal of cardiovascular electrophysiology, 20(10), 1137-1141. https://doi.org/10.1111/j.1540-8167.2009.01508.x

Genetic modulation of brugada syndrome by a common polymorphism. / Lizotte, Eric; Junttila, M. Juhani; Dube, Marie Pierre; Hong, Kui; Benito, Begona; De Zutter, Marc; Henkens, Stefan; Sarkozy, Andrea; Huikuri, Heikki V.; Towbin, Jeffrey; Vatta, Matteo; Brugada, Pedro; Brugada, Josep; Brugada, Ramon.

In: Journal of cardiovascular electrophysiology, Vol. 20, No. 10, 03.11.2009, p. 1137-1141.

Research output: Contribution to journalArticle

Lizotte, E, Junttila, MJ, Dube, MP, Hong, K, Benito, B, De Zutter, M, Henkens, S, Sarkozy, A, Huikuri, HV, Towbin, J, Vatta, M, Brugada, P, Brugada, J & Brugada, R 2009, 'Genetic modulation of brugada syndrome by a common polymorphism', Journal of cardiovascular electrophysiology, vol. 20, no. 10, pp. 1137-1141. https://doi.org/10.1111/j.1540-8167.2009.01508.x
Lizotte E, Junttila MJ, Dube MP, Hong K, Benito B, De Zutter M et al. Genetic modulation of brugada syndrome by a common polymorphism. Journal of cardiovascular electrophysiology. 2009 Nov 3;20(10):1137-1141. https://doi.org/10.1111/j.1540-8167.2009.01508.x
Lizotte, Eric ; Junttila, M. Juhani ; Dube, Marie Pierre ; Hong, Kui ; Benito, Begona ; De Zutter, Marc ; Henkens, Stefan ; Sarkozy, Andrea ; Huikuri, Heikki V. ; Towbin, Jeffrey ; Vatta, Matteo ; Brugada, Pedro ; Brugada, Josep ; Brugada, Ramon. / Genetic modulation of brugada syndrome by a common polymorphism. In: Journal of cardiovascular electrophysiology. 2009 ; Vol. 20, No. 10. pp. 1137-1141.
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abstract = "Genetic Modulation of Brugada Syndrome by a Common Polymorphism. Background: Brugada syndrome predisposes some subjects to ventricular tachyarrhythmias and sudden cardiac death. Mutations in SCN5A gene have been associated with ∼25{\%} of Brugada syndrome patients. A common variant in SCN5A, H558R has shown to improve sodium channel activity in mutated channels. We studied whether common variant H558R has any clinical implications in the phenotype of Brugada syndrome. Methods: Our study population consisted of Brugada syndrome subjects 75 with SCN5A mutation and 92 without SCN5A mutation. Their mean age was 39 ± 15 and 42 ± 17 years, and 65{\%} and 86{\%} were male, respectively. We measured PR-, QRS-, QTc-intervals from leads II and V2 of the 12-lead ECG. We also evaluated J-point amplitude from lead V2 and R'/S ratio from lead aVR (the {"}aVR sign{"}). The H558R (A→G) genotype was detected with direct sequencing of the SCN5A gene. Results: The AA genotype carriers had longer QRS duration in lead II (P = 0.017) and higher J-point elevation in lead V2 (P = 0.013), higher {"}aVR sign{"} (P = 0.005) and a trend toward more subjects with symptoms (P = 0.067) than G allele carriers. None of the results were significant in Brugada syndrome subjects without SCN5A mutation. Conclusion: The common variant H558R seems to be a genetic modulator of Brugada syndrome among carriers of a SCN5A mutation, in whom the presence of the less common allele G improves the ECG characteristics and clinical phenotype. (J Cardiovasc Electrophysiol, Vol. pp. 1137-1141)",
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AU - Junttila, M. Juhani

AU - Dube, Marie Pierre

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AU - Benito, Begona

AU - De Zutter, Marc

AU - Henkens, Stefan

AU - Sarkozy, Andrea

AU - Huikuri, Heikki V.

AU - Towbin, Jeffrey

AU - Vatta, Matteo

AU - Brugada, Pedro

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N2 - Genetic Modulation of Brugada Syndrome by a Common Polymorphism. Background: Brugada syndrome predisposes some subjects to ventricular tachyarrhythmias and sudden cardiac death. Mutations in SCN5A gene have been associated with ∼25% of Brugada syndrome patients. A common variant in SCN5A, H558R has shown to improve sodium channel activity in mutated channels. We studied whether common variant H558R has any clinical implications in the phenotype of Brugada syndrome. Methods: Our study population consisted of Brugada syndrome subjects 75 with SCN5A mutation and 92 without SCN5A mutation. Their mean age was 39 ± 15 and 42 ± 17 years, and 65% and 86% were male, respectively. We measured PR-, QRS-, QTc-intervals from leads II and V2 of the 12-lead ECG. We also evaluated J-point amplitude from lead V2 and R'/S ratio from lead aVR (the "aVR sign"). The H558R (A→G) genotype was detected with direct sequencing of the SCN5A gene. Results: The AA genotype carriers had longer QRS duration in lead II (P = 0.017) and higher J-point elevation in lead V2 (P = 0.013), higher "aVR sign" (P = 0.005) and a trend toward more subjects with symptoms (P = 0.067) than G allele carriers. None of the results were significant in Brugada syndrome subjects without SCN5A mutation. Conclusion: The common variant H558R seems to be a genetic modulator of Brugada syndrome among carriers of a SCN5A mutation, in whom the presence of the less common allele G improves the ECG characteristics and clinical phenotype. (J Cardiovasc Electrophysiol, Vol. pp. 1137-1141)

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