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Makarawate, P.* ; Glinge, C.* ; Khongphatthanayothin, A.* ; Walsh, R.* ; Mauleekoonphairoj, J.* ; Amnueypol, M.* ; Prechawat, S.* ; Wongcharoen, W.* ; Krittayaphong, R.* ; Anannab, A.* ; Lichtner, P. ; Meitinger, T. ; Tjong, F.V.Y.* ; Lieve, K.V.V.* ; Amin, A.S.* ; Sahasatas, D.* ; Ngarmukos, T.* ; Wichadakul, D.* ; Payungporn, S.* ; Sutjaporn, B.* ; Wandee, P.* ; Poovorawan, Y.* ; Tfelt-Hansen, J.* ; Tanck, M.W.T.* ; Tadros, R.* ; Wilde, A.A.M.* ; Bezzina, C.R.* ; Veerakul, G.* ; Nademanee, K.*

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

Heart Rhythm 17, 2145-2153 (2020)
DOI PMC
Open Access Green as soon as Postprint is submitted to ZB.
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 x 10(-10)). Conditional analysis identified a novel independent signal in the same locus (rs6767797; OR 2.3; P = 2.7 x 10(-10)).The second locus was near HEY2 (lead marker rs3734634; OR 2.5; P = 7 x 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.
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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords Brugada Syndrome ; Genome-wide Association Study ; Genetics ; Scn5a ; Thailand; Scn5a Mutations; Death; Hey2
ISSN (print) / ISBN 1547-5271
e-ISSN 1556-3871
Journal Heart Rhythm
Quellenangaben Volume: 17, Issue: 12, Pages: 2145-2153 Article Number: , Supplement: ,
Publisher Elsevier
Publishing Place Ste 800, 230 Park Ave, New York, Ny 10169 Usa
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Institute of Human Genetics (IHG)
Grants Dutch Heart Foundation
Bumrungrad Hospital, Bangkok, Thailand
Thailand Research Fund
National Science and Technology Development Agency
Center of Excellence in Clinical Virology, Chulalongkorn University
King Chulalongkorn Memorial Hospital
Dutch Heart Foundation, Netherlands
Netherlands Organization for Scientific Research (VICI Fellowship)
Canadian Heart Rhythm Society's George Mines Award
European Society of Cardiology research award
Philippa and Marvin Carsley Cardiology Chair
National Research Council of Thailand