Very early-onset lone atrial fibrillation patients have a high prevalence of rare variants in genes previously associated with atrial fibrillation.
Heart Rhythm
; 11(2): 246-51, 2014 Feb.
Article
en En
| MEDLINE
| ID: mdl-24144883
BACKGROUND: Atrial fibrillation (AF) is the most common cardiac arrhythmia. Currently, 14 genes important for ion channel function, intercellular signaling, and homeostatic control have been associated with AF. OBJECTIVE: We hypothesized that rare genetic variants in genes previously associated with AF had a higher prevalence in early-onset lone AF patients than in the background population. METHODS: Sequencing results of KCNQ1, KCNH2, SCN5A, KCNA5, KCND3, KCNE1, 2, 5, KCNJ2, SCN1-3B, NPPA, and GJA5 from 192 early-onset lone AF patients were compared with data from the National Heart, Lung, and Blood Institute Exome Variant Server consisting of 6503 persons from 18 different cohort studies. RESULTS: Among the lone AF patients, 29 (7.6%) alleles harbored a novel or very rare variant (minor allele frequency <0.1 in the Exome Variant Server), a frequency that was significantly higher than what was found in the reference database (4.1%; with minor allele frequency <0.1; P = .0012). Previously published electrophysiological data showed that 96% (n = 23) of the rare variants that has been functionally investigated (n = 24) displayed significant functional changes. CONCLUSIONS: We report a much higher prevalence of rare variants in genes associated with AF in early-onset lone AF patients than in the background population. By presenting these data, we believe that we are the first to provide quantitative evidence for the role of rare variants across AF susceptibility genes as a possible pathophysiological substrate for AF.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Fibrilación Atrial
Tipo de estudio:
Observational_studies
/
Prevalence_studies
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Risk_factors_studies
Límite:
Adult
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Female
/
Humans
Idioma:
En
Revista:
Heart Rhythm
Año:
2014
Tipo del documento:
Article