| Title: | Genetic Basis of Early Onset Atrial Fibrillation in Patients without Risk Factors |
| Journal: | Journal of Cardiovascular Development and Disease |
| Published: | 28 Feb 2023 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/36975868/ |
| DOI: | https://doi.org/10.3390/jcdd10030104 |
| URL: | https://www.mdpi.com/2308-3425/10/3/104/pdf?version=1677569659 |
Publication 7921
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Abstract
BACKGROUND: Atrial fibrillation (AF) is the most common arrhythmia and typically occurs in elderly patients with other cardiovascular and extracardiac diseases. However, up to 15% of AF develops without any related risk factors. Recently, the role of genetic factors has been highlighted in this particular form of AF. AIMS: The aims of this study were to determine the prevalence of pathogenic variants in early-onset AF in patients without known disease-related risk factors and to identify any structural cardiac abnormalities in these patients. MATERIALS AND METHODS: We conducted exome sequencing and interpretation in 54 risk factor-free early-onset AF patients and further validated our findings in a similar AF patient cohort from the UK Biobank. RESULTS: Pathogenic/likely pathogenic variants were found in 13/54 (24%) patients. The variants were identified in cardiomyopathy-related and not arrhythmia-related genes. The majority of the identified variants were TTN gene truncating variants (TTNtvs) (9/13 (69%) patients). We also observed two TTNtvs founder variants in the analysed population-c.13696C>T p.(Gln4566Ter) and c.82240C>T p.(Arg27414Ter). Pathogenic/likely pathogenic variants were found in 9/107 (8%) individuals from an independent similar AF patient cohort from the UK Biobank. In correspondence with our Latvian patients, only variants in cardiomyopathy-associated genes were identified. In five (38%) of the thirteen Latvian patients with pathogenic/likely pathogenic variants, dilation of one or both ventricles was identified on a follow-up cardiac magnetic resonance scan. CONCLUSIONS: We observed a high prevalence of pathogenic/likely pathogenic variants in cardiomyopathy-associated genes in patients with risk factor-free early-onset AF. Moreover, our follow-up imaging data indicate that these types of patients are at risk of developing ventricular dilation. Furthermore, we identified two TTNtvs founder variants in our Latvian study population.6 Authors
- Irina Rudaka
- Baiba Vilne
- Jekaterina Isakova
- Oskars Kalejs
- Linda Gailite
- Dmitrijs Rots
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