Publication:
Common and rare susceptibility genetic variants predisposing to Brugada syndrome in Thailand

Issued Date

2020-12-01

Resource Type

Article

ISSN

15563871
15475271

DOI

10.1016/j.hrthm.2020.06.027

Other identifier(s)

2-s2.0-85091722293

Rights

Mahidol University

Rights Holder(s)

SCOPUS

Bibliographic Citation

Heart Rhythm. Vol.17, No.12 (2020), 2145-2153

Suggested Citation

Pattarapong Makarawate, Charlotte Glinge, Apichai Khongphatthanayothin, Roddy Walsh, John Mauleekoonphairoj, Montawatt Amnueypol, Somchai Prechawat, Wanwarang Wongcharoen, Rungroj Krittayaphong, Alisara Anannab, Peter Lichtner, Thomas Meitinger, Fleur V.Y. Tjong, Krystien V.V. Lieve, Ahmad S. Amin, Dujdao Sahasatas, Tachapong Ngarmukos, Duangdao Wichadakul, Sunchai Payungporn, Boosamas Sutjaporn, Pharawee Wandee, Yong Poovorawan, Jacob Tfelt-Hansen, Michael W.T. Tanck, Rafik Tadros, Arthur A.M. Wilde, Connie R. Bezzina, Gumpanart Veerakul, Koonlawee Nademanee Common and rare susceptibility genetic variants predisposing to Brugada syndrome in Thailand. Heart Rhythm. Vol.17, No.12 (2020), 2145-2153. doi:10.1016/j.hrthm.2020.06.027 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/60547

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Title

Common and rare susceptibility genetic variants predisposing to Brugada syndrome in Thailand

Author(s)

Pattarapong Makarawate
 Charlotte Glinge
 Apichai Khongphatthanayothin
 Roddy Walsh
 John Mauleekoonphairoj
 Montawatt Amnueypol
 Somchai Prechawat
 Wanwarang Wongcharoen
 Rungroj Krittayaphong
 Alisara Anannab
 Peter Lichtner
 Thomas Meitinger
 Fleur V.Y. Tjong
 Krystien V.V. Lieve
 Ahmad S. Amin
 Dujdao Sahasatas
 Tachapong Ngarmukos
 Duangdao Wichadakul
 Sunchai Payungporn
 Boosamas Sutjaporn
 Pharawee Wandee
 Yong Poovorawan
 Jacob Tfelt-Hansen
 Michael W.T. Tanck
 Rafik Tadros
 Arthur A.M. Wilde
 Connie R. Bezzina
 Gumpanart Veerakul
 Koonlawee Nademanee

Other Contributor(s)

Københavns Universitet
 Chulalongkorn University
 Helmholtz Center Munich German Research Center for Environmental Health
 Bumrungrad International Hospital
 Khon Kaen University
 Faculty of Medicine, Ramathibodi Hospital, Mahidol University
 Institut de Cardiologie de Montreal
 Faculty of Medicine, Siriraj Hospital, Mahidol University
 Rigshospitalet
 Universiteit van Amsterdam
 Chiang Mai University
 Bangkok Heart Hospital
 European Reference Network for Rare and Low Prevalence Complex Diseases of the Heart (ERN GUARDHEART
 Central Chest Institute of Thailand

Abstract

© 2020 Heart Rhythm Society Background: Mutations in SCN5A are rarely found in Thai patients with Brugada syndrome (BrS). Recent evidence suggested that common genetic variations may underlie BrS in a complex inheritance model. Objective: The purpose of this study was to find common and rare/low-frequency genetic variants predisposing to BrS in persons in Thailand. Methods: We conducted a genome-wide association study (GWAS) to explore the association of common variants in 154 Thai BrS cases and 432 controls. We sequenced SCN5A in 131 cases and 205 controls. Variants were classified according to current guidelines, and case-control association testing was performed for rare and low-frequency variants. Results: Two loci were significantly associated with BrS. The first was near SCN5A/SCN10A (lead marker rs10428132; odds ratio [OR] 2.4; P = 3 × 10–10). Conditional analysis identified a novel independent signal in the same locus (rs6767797; OR 2.3; P = 2.7 × 10–10). The second locus was near HEY2 (lead marker rs3734634; OR 2.5; P = 7 × 10–9). Rare (minor allele frequency [MAF] <0.0001) coding variants in SCN5A were found in 8 of the 131 cases (6.1% in cases vs 2.0% in controls; P = .046; OR 3.3; 95% confident interval [CI] 1.0–11.1), but an enrichment of low-frequency (MAF<0.001 and >0.0001) variants also was observed in cases, with 1 variant (SCN5A: p.Arg965Cys) detected in 4.6% of Thai BrS patients vs 0.5% in controls (P = 0.015; OR 9.8; 95% CI 1.2–82.3). Conclusion: The genetic basis of BrS in Thailand includes a wide spectrum of variant frequencies and effect sizes. As previously shown in European and Japanese populations, common variants near SCN5A and HEY2 are associated with BrS in the Thai population, confirming the transethnic transferability of these 2 major BrS loci.

Keyword(s)

Medicine

Availability

URI

https://repository.li.mahidol.ac.th/handle/20.500.14594/60547

Collections

Scopus 2020