Genetic Basis of Early Onset Atrial Fibrillation in Patients without Risk Factors

Irina Rudaka; Baiba Vilne; Jekaterina Isakova; Oskars Kalejs; Linda Gailite; Dmitrijs Rots

doi:10.3390/jcdd10030104

Genetic Basis of Early Onset Atrial Fibrillation in Patients without Risk Factors

J Cardiovasc Dev Dis. 2023 Feb 28;10(3):104. doi: 10.3390/jcdd10030104.

Authors

Irina Rudaka^{1

2}, Baiba Vilne³, Jekaterina Isakova¹, Oskars Kalejs², Linda Gailite¹, Dmitrijs Rots¹

Affiliations

¹ Scientific Laboratory of Molecular Genetics, Rīga Stradiņš University, LV-1007 Riga, Latvia.
² Latvian Cardiology Centre, Pauls Stradiņš Clinical University Hospital, LV-1002 Riga, Latvia.
³ Bioinformatics Laboratory, Rīga Stradiņš University, LV-1007 Riga, Latvia.

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.

Keywords: early-onset atrial fibrillation; genetics; next-generation sequencing; pathogenic variants.

Grants and funding

This research was funded by the Latvian Council of Science, project, “The role of clonal hemato-poiesis of indeterminate potential as a potential driver of cardiovascular diseases and its associ-ation with clinical outcome”, project No. lzp-2021/1-0293.