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

Adult Brugada Syndrome / epidemiology DNA / genetics DNA Mutational Analysis Female Gene Frequency Genetic Predisposition to Disease Genetic Variation Genome-Wide Association Study / methods Humans Incidence Male Middle Aged Mutation NAV1.5 Voltage-Gated Sodium Channel / genetics Phenotype Rare Diseases Retrospective Studies Thailand / epidemiology

Brugada syndrome Genetics Genome-wide association study SCN5A Thailand

Journal

Heart rhythm

ISSN: 1556-3871

Titre abrégé: Heart Rhythm

Pays: United States

ID NLM: 101200317

Informations de publication

Date de publication:
12 2020

Historique:

received: 14 04 2020

revised: 06 06 2020

accepted: 23 06 2020

pubmed: 4 7 2020

medline: 30 9 2021

entrez: 4 7 2020

Statut: ppublish

Résumé

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. The purpose of this study was to find common and rare/low-frequency genetic variants predisposing to BrS in persons in Thailand. 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. Two loci were significantly associated with BrS. The first was near SCN5A/SCN10A (lead marker rs10428132; odds ratio [OR] 2.4; P = 3 × 10 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.

Sections du résumé

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

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.

Identifiants

DOI: 10.1016/j.hrthm.2020.06.027 PMID: 32619740

pubmed: 32619740

pii: S1547-5271(20)30626-3

doi: 10.1016/j.hrthm.2020.06.027

pii:

doi:

Substances chimiques

NAV1.5 Voltage-Gated Sodium Channel 0

SCN5A protein, human 0

DNA 9007-49-2

Banques de données

ClinicalTrials.gov

['NCT04232787']

Types de publication

Journal Article Multicenter Study Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

Pagination

2145-2153