Research
Print page Print page
Switch language
Rigshospitalet - a part of Copenhagen University Hospital
Published

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

Research output: Contribution to journalJournal articleResearchpeer-review

  1. Long QT syndrome type 1 and 2 patients respond differently to arrhythmic triggers: The TriQarr in vivo study

    Research output: Contribution to journalJournal articleResearchpeer-review

  2. Incidence of atrial fibrillation in conjunction with breast cancer

    Research output: Contribution to journalJournal articleResearchpeer-review

  1. Clopidogrel, prasugrel, and ticagrelor for all-comers with ST-segment elevation myocardial infarction

    Research output: Contribution to journalJournal articleResearchpeer-review

  2. Witnessed and unwitnessed sudden cardiac death: a nationwide study of persons aged 1-35 years

    Research output: Contribution to journalJournal articleResearchpeer-review

  3. Cardiac arrhythmias in patients hospitalized with COVID-19: The ACOVID study

    Research output: Contribution to journalJournal articleResearchpeer-review

  4. Natural History and Clinical Characteristics of the First 10 Danish Families With Familial ST-Depression Syndrome

    Research output: Contribution to journalLetterResearchpeer-review

  • 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
View graph of relations

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.

Original languageEnglish
JournalHeart Rhythm
Volume17
Issue number12
Pages (from-to)2145-2153
Number of pages9
ISSN1547-5271
DOIs
Publication statusPublished - Dec 2020

ID: 62373982