Genetic aspects of lone atrial fibrillation in patients without structural heart disease

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Background: Atrial fibrillation (AF) is the most common cardiac arrhythmia. Among patients with AF the subgroup posessing AF without traditional risk factors is differentiated. Such patients are commonly referred as having “lone AF” and comprise 10–20% of all cases. A number of studies have demonstrated that the background of AF, and in particular lone AF, have a substantial genetic component.

Aims: To evaluate the influence of gene polymorphism to the development of atrial fibrillation in patients without concomitant valvular pathology and coronary artery disease.

Materials and methods: The study included 174 patients with atrial fibrillation and 124 controls without any cardiovascular pathology. All patients were divided into two subgroups: with “lone AF” (n=94) and with concomitant arterial hypertension (n=80). All patients underwent a complex of clinical, instrumental (ECG, echocardiography, computed tomography of the pulmonary veins) and laboratory tests (thyroid hormones, inflammatory markers, fibrosis), as well as genetic analysis (determination of single nucleotide polymorphisms described as AF risk factors in genes AGXT2, PDE4D, SLN, SCN5A, PITX2, PRRX1, ZFHX3, TBX5, CAV1 и HCN4).

Results: For the rare polymorphisms rs12291814 (SLN) and rs137854601 (SCN5A) wasn’t found anyone carrier of the minor allele (C and A, respectively). In the both patient subgroups the minor allele T of rs2200733 in PITX2 (OR=3.18, p<0.0001), minor allele G of rs3903239 in PRRX1, and minor alleles A of 2 polymorphisms rs2106261 and rs7193343 in ZFHX3 gene were revealed as risk factor of AF (OR=2.96, p<0.0001, OR=2.02, p=0.0045, OR=1.64, p=0.04, respectively). We also revealed significant difference between AF and control groups for rs3807989 in CAV1: homozygotic state of minor allele A has a protective effect on the development of arrhythmias (OR=0.39).

Conclusions: We revealed the association between the polymorphisms in genes regulating transcription and the development of atrial fibrillation. These polymorphisms have already described but their frequencies have never investigated in Russian population. But the polymorphisms influence to gene functions stays unclear, although attempts to investigate relationship between genotype and gene expression have been made. When the relationship will be discovered it can help us to modify our approach in treatment to patients with atrial fibrillation.

Elena Z. Golukhova

Bakoulev Center for Cardiovascular Surgery RAMS

ORCID iD: 0000-0002-6252-0322
SPIN-code: 9334-5672

Russian Federation, 135, Roublevskoye shosse, 121552 Moscow

MD, PhD, Professor

Aygerim Z. Zholbaeva

Bakoulev Center for Cardiovascular Surgery RAMS

Author for correspondence.
ORCID iD: 0000-0002-6918-7016
SPIN-code: 3348-5569

Russian Federation, 135, Roublevskoye shosse, 121552 Moscow

Mari G. Arakelyan

Bakoulev Center for Cardiovascular Surgery RAMS

ORCID iD: 0000-0001-5089-0169
SPIN-code: 9161-9888

Russian Federation, 135, Roublevskoye shosse, 121552 Moscow

Naida I. Bulaeva

Bakoulev Center for Cardiovascular Surgery RAMS

ORCID iD: 0000-0002-5091-0518
SPIN-code: 8979-7098

Russian Federation, 135, Roublevskoye shosse, 121552 Moscow


Michail M. Minashkin

Diaem Ltd

ORCID iD: 0000-0002-0726-7563
SPIN-code: 5693-0057

Russian Federation, Moscow

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