Genotype-Phenotype Correlation of <i>SCN5A</i> Genotype in Patients With Brugada Syndrome and Arrhythmic Events: Insights From the SABRUS in 392 Probands
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- Anat Milman
- Leviev Heart Institute, The Chaim Sheba Medical Center, Tel Hashomer, Israel (A. Milman).
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- Elijah R. Behr
- European Reference Network for Rare and Low Prevalence Complex Diseases of the Heart (E.R.B., D.C.J., A.A., J.-B.G., P.G.P., Y.M., A. Mazzanti, C.H.J., D.C., J.T.-H., S.G.P., A.A.M.W., V.P.).
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- Belinda Gray
- Cardiovascular Clinical Academic Group, St George’s, University of London & St. George’s University Hospitals NHS Foundation Trust, United Kingdom (E.R.B., B.G., D.C.J.).
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- David C. Johnson
- European Reference Network for Rare and Low Prevalence Complex Diseases of the Heart (E.R.B., D.C.J., A.A., J.-B.G., P.G.P., Y.M., A. Mazzanti, C.H.J., D.C., J.T.-H., S.G.P., A.A.M.W., V.P.).
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- Antoine Andorin
- European Reference Network for Rare and Low Prevalence Complex Diseases of the Heart (E.R.B., D.C.J., A.A., J.-B.G., P.G.P., Y.M., A. Mazzanti, C.H.J., D.C., J.T.-H., S.G.P., A.A.M.W., V.P.).
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- Aviram Hochstadt
- Sackler School of Medicine, Tel Aviv University, Israel (A. Milman, A.H., B.B.).
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- Jean-Baptiste Gourraud
- European Reference Network for Rare and Low Prevalence Complex Diseases of the Heart (E.R.B., D.C.J., A.A., J.-B.G., P.G.P., Y.M., A. Mazzanti, C.H.J., D.C., J.T.-H., S.G.P., A.A.M.W., V.P.).
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- Shingo Maeda
- Heart Rhythm Center, Tokyo Medical and Dental University, Tokyo, Japan (S.M., Y.T., K.H.).
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- Yoshihide Takahashi
- Heart Rhythm Center, Tokyo Medical and Dental University, Tokyo, Japan (S.M., Y.T., K.H.).
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- Jimmy JM Juang
- Cardiovascular Center and Division of Cardiology, National Taiwan University Hospital & University College of Medicine, Taipei (J.J.M.J.).
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- Sung-Hwan Kim
- Division of Cardiology, College of Medicine, The Catholic University of Korea, Seoul, Korea (S.-H.K.).
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- Tsukasa Kamakura
- Division of Arrhythmia and Electrophysiology, National Cerebral and Cardiovascular Center, Osaka, Japan (T.K., T.A., K.F.K.).
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- Takeshi Aiba
- Division of Arrhythmia and Electrophysiology, National Cerebral and Cardiovascular Center, Osaka, Japan (T.K., T.A., K.F.K.).
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- Pieter G. Postema
- European Reference Network for Rare and Low Prevalence Complex Diseases of the Heart (E.R.B., D.C.J., A.A., J.-B.G., P.G.P., Y.M., A. Mazzanti, C.H.J., D.C., J.T.-H., S.G.P., A.A.M.W., V.P.).
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- Yuka Mizusawa
- European Reference Network for Rare and Low Prevalence Complex Diseases of the Heart (E.R.B., D.C.J., A.A., J.-B.G., P.G.P., Y.M., A. Mazzanti, C.H.J., D.C., J.T.-H., S.G.P., A.A.M.W., V.P.).
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- Isabelle Denjoy
- Service de Cardiologie et CNMR Maladies Cardiaques Héréditaires Rares, Hôpital Bichat & Université Paris Diderot, Sorbonne, France (I.D., A.L.).
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- Carla Giustetto
- Division of Cardiology, University of Torino, Department of Medical Sciences, Città della Salute e della Scienza Hospital, Italy (C.G., F.G.).
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- Zhengrong Huang
- Department of Cardiology, the First Affiliated Hospital of Xiamen University, Fujian, China (Z.H.).
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- Georgia Sarquella-Brugada
- Pediatric Arrhythmias, Electrophysiology and Sudden Death Unit Cardiology, Department Hospital Sant Joan de Déu, Barcelona - Universitat de Barcelona, Spain (G.S.-B.).
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- Andrea Mazzanti
- European Reference Network for Rare and Low Prevalence Complex Diseases of the Heart (E.R.B., D.C.J., A.A., J.-B.G., P.G.P., Y.M., A. Mazzanti, C.H.J., D.C., J.T.-H., S.G.P., A.A.M.W., V.P.).
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- Camilla H. Jespersen
- European Reference Network for Rare and Low Prevalence Complex Diseases of the Heart (E.R.B., D.C.J., A.A., J.-B.G., P.G.P., Y.M., A. Mazzanti, C.H.J., D.C., J.T.-H., S.G.P., A.A.M.W., V.P.).
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- Elena Arbelo
- Cardiovascular Institute, Hospital Clinic and IDIBAPS, Barcelona, Catalonia, Spain (E.A., J.B.).
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- Ramon Brugada
- Cardiovascular Genetics Center, University of Girona-IDIBGI, Spain (R.B.).
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- Leonardo Calo
- Division of Cardiology, Policlinico Casilino, Roma, Italy (L.C.).
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- Domenico Corrado
- European Reference Network for Rare and Low Prevalence Complex Diseases of the Heart (E.R.B., D.C.J., A.A., J.-B.G., P.G.P., Y.M., A. Mazzanti, C.H.J., D.C., J.T.-H., S.G.P., A.A.M.W., V.P.).
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- Ruben Casado-Arroyo
- Department of Cardiology, Erasme University Hospital, Université Libre de Bruxelles, Brussels, Belgium (R.C.-A.).
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- Giuseppe Allocca
- Division of Cardiology, Hospital of Peschiera del Garda, Veneto, Italy (G.A., P.D.).
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- Masahiko Takagi
- Division of Cardiac Arrhythmia, Kansai Medical University Medical Center, Moriguchi, Japan (M.T.).
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- Pietro Delise
- Division of Cardiology, Hospital of Peschiera del Garda, Veneto, Italy (G.A., P.D.).
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- Josep Brugada
- Cardiovascular Institute, Hospital Clinic and IDIBAPS, Barcelona, Catalonia, Spain (E.A., J.B.).
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- Jacob Tfelt-Hansen
- European Reference Network for Rare and Low Prevalence Complex Diseases of the Heart (E.R.B., D.C.J., A.A., J.-B.G., P.G.P., Y.M., A. Mazzanti, C.H.J., D.C., J.T.-H., S.G.P., A.A.M.W., V.P.).
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- Silvia G. Priori
- European Reference Network for Rare and Low Prevalence Complex Diseases of the Heart (E.R.B., D.C.J., A.A., J.-B.G., P.G.P., Y.M., A. Mazzanti, C.H.J., D.C., J.T.-H., S.G.P., A.A.M.W., V.P.).
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- Christian Veltmann
- Hannover Heart Rhythm Center, Department of Cardiology & Angiology, Hannover Medical School, Hannover, Germany (C.V.).
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- Gan-Xin Yan
- Lankenau Medical Center, Wynnewood, PA (G.-X.Y.).
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- Pedro Brugada
- Heart Rhythm Management Centre, UZ-VUB, Brussels, Belgium (G.C., P.B.).
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- Fiorenzo Gaita
- Division of Cardiology, University of Torino, Department of Medical Sciences, Città della Salute e della Scienza Hospital, Italy (C.G., F.G.).
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- Antoine Leenhardt
- Service de Cardiologie et CNMR Maladies Cardiaques Héréditaires Rares, Hôpital Bichat & Université Paris Diderot, Sorbonne, France (I.D., A.L.).
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- Arthur A.M. Wilde
- European Reference Network for Rare and Low Prevalence Complex Diseases of the Heart (E.R.B., D.C.J., A.A., J.-B.G., P.G.P., Y.M., A. Mazzanti, C.H.J., D.C., J.T.-H., S.G.P., A.A.M.W., V.P.).
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- Kengo F. Kusano
- Division of Arrhythmia and Electrophysiology, National Cerebral and Cardiovascular Center, Osaka, Japan (T.K., T.A., K.F.K.).
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- Gi-Byoung Nam
- Division of Cardiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea (G.-B.N.).
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- Kenzo Hirao
- Heart Rhythm Center, Tokyo Medical and Dental University, Tokyo, Japan (S.M., Y.T., K.H.).
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- Vincent Probst
- European Reference Network for Rare and Low Prevalence Complex Diseases of the Heart (E.R.B., D.C.J., A.A., J.-B.G., P.G.P., Y.M., A. Mazzanti, C.H.J., D.C., J.T.-H., S.G.P., A.A.M.W., V.P.).
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- Bernard Belhassen
- Sackler School of Medicine, Tel Aviv University, Israel (A. Milman, A.H., B.B.).
説明
<jats:sec> <jats:title>Background:</jats:title> <jats:p> Brugada syndrome (BrS) is associated with mutations in the cardiac sodium channel gene, <jats:italic>SCN5A.</jats:italic> However, genetic studies of patients with BrS with arrhythmic events have been limited. We sought to compare various clinical, ECG, and electrophysiological parameters according to <jats:italic>SCN5A</jats:italic> genotype in a large cohort of BrS probands with first arrhythmic event. </jats:p> </jats:sec> <jats:sec> <jats:title>Methods:</jats:title> <jats:p> Survey on Arrhythmic Events in Brugada Syndrome is a survey of 10 Western and 4 Asian countries, gathering 678 patients with BrS with first arrhythmic event. Only probands were included, and <jats:italic>SCN5A</jats:italic> genotype adjudicated. Patients without appropriate genetic data were excluded. Associations of genotype with clinical features were analyzed. </jats:p> </jats:sec> <jats:sec> <jats:title>Results:</jats:title> <jats:p> The study group comprised 392 probands: 92 (23.5%) <jats:italic>SCN5A+</jats:italic> (44 pathogenic/likely pathogenic [P/LP] and 48 variants of unknown significance) and 300 (76.5%) <jats:italic>SCN5A−.</jats:italic> <jats:italic>SCN5A</jats:italic> missense variants and the patients hosting them were similar regardless of adjudication. A higher proportion of patients with P/LP were pediatric (<16 years) compared with <jats:italic>SCN5A−</jats:italic> (11.4% versus 3%, <jats:italic>P</jats:italic> =0.023). The proportion of females was higher among patients with P/LP compared with <jats:italic>SCN5A</jats:italic> − (18.2% versus 6.3%, <jats:italic>P</jats:italic> =0.013). P/LP probands were more likely to have a family history of sudden cardiac death compared with <jats:italic>SCN5A</jats:italic> − (41.9% versus 16.8%, <jats:italic>P</jats:italic> <0.001). A higher proportion of patients with P/LP were White compared with <jats:italic>SCN5A−</jats:italic> (87.5% versus 47%, <jats:italic>P</jats:italic> <0.001). Ethnicity (odds ratio, 5.41 [2.8–11.19], <jats:italic>P</jats:italic> <0.001) and family history of sudden cardiac death (odds ratio, 2.73 [1.28–5.82], <jats:italic>P</jats:italic> =0.009) were independent variables associated with P/LP genotype following logistic regression. </jats:p> </jats:sec> <jats:sec> <jats:title>Conclusions:</jats:title> <jats:p> The genetic basis of BrS has a complex relationship with gender, ethnicity, and age. Probands hosting a P/LP variant tended to experience their first arrhythmic event at a younger age and to have events triggered by fever compared with patients with <jats:italic>SCN5A−</jats:italic> . In addition, they were more likely to be White and to have family history of sudden cardiac death. Among females, a P/LP variant suggests an increased risk of being symptomatic. This association should be further studied on an ethnically specific basis in large prospectively collected international cohorts. </jats:p> </jats:sec>
収録刊行物
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- Circulation: Genomic and Precision Medicine
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Circulation: Genomic and Precision Medicine 14 (5), 2021-10
Ovid Technologies (Wolters Kluwer Health)
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キーワード
- Adult
- Male
- NAV1.5 Voltage-Gated Sodium Channel -- genetics
- Adolescent
- Genotype
- genotype
- [SDV]Life Sciences [q-bio]
- 610
- Ethnic Groups
- Sex Factor
- Brugada syndrome; ethnic groups; genotype; mutation; sudden cardiac death
- ethnic groups
- sudden cardiac death
- NAV1.5 Voltage-Gated Sodium Channel
- ethnic group
- Electrocardiography
- Sex Factors
- *sudden cardiac death
- 616
- Humans
- Brugada syndrome
- Aged
- *Brugada syndrome
- Sciences bio-médicales et agricoles
- Middle Aged
- *ethnic groups
- *mutation
- Brugada Syndrome -- genetics -- physiopathology
- Female
- *genotype
- mutation
- Human
詳細情報 詳細情報について
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- CRID
- 1360857593739297408
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- ISSN
- 25748300
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- 資料種別
- journal article
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- データソース種別
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- Crossref
- KAKEN
- OpenAIRE