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. 2018 Sep 10:2018:4862480.
doi: 10.1155/2018/4862480. eCollection 2018.

Atrial Structural Remodeling Gene Variants in Patients with Atrial Fibrillation

Rosa Doñate Puertas  1 , Gilles Millat  1   2   3 , Isabelle Ernens  4 , Vincent Gache  1 , Samuel Chauveau  5 , Elodie Morel  5 , Emilie Christin  1 , Nathalie Couturier  1 , Yvan Devaux  4 , Philippe Chevalier  1   5
Affiliations

Atrial Structural Remodeling Gene Variants in Patients with Atrial Fibrillation

Rosa Doñate Puertas et al. Biomed Res Int. .

Abstract

Atrial fibrillation (AF) is a common arrhythmia for which the genetic studies mainly focused on the genes involved in electrical remodeling, rather than left atrial muscle remodeling. To identify rare variants involved in atrial myopathy using mutational screening, a high-throughput next-generation sequencing (NGS) workflow was developed based on a custom AmpliSeq™ panel of 55 genes potentially involved in atrial myopathy. This workflow was applied to a cohort of 94 patients with AF, 76 with atrial dilatation and 18 without. Bioinformatic analyses used NextGENe® software and in silico tools for variant interpretation. The AmpliSeq custom-made panel efficiently explored 96.58% of the targeted sequences. Based on in silico analysis, 11 potentially pathogenic missense variants were identified that were not previously associated with AF. These variants were located in genes involved in atrial tissue structural remodeling. Three patients were also carriers of potential variants in prevalent arrhythmia-causing genes, usually associated with AF. Most of the variants were found in patients with atrial dilatation (n=9, 82%). This NGS approach was a sensitive and specific method that identified 11 potentially pathogenic variants, which are likely to play roles in the predisposition to left atrial myopathy. Functional studies are needed to confirm their pathogenicity.

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Figures

Figure 1
Figure 1
Filtering steps. Decision tree for exploration of genes related to atrial fibrillation using a next-generation sequencing approach to detect mutations, based on a custom AmpliSeq library and Ion Torrent PGM sequencing. Abbreviations: MAF = minor allele frequency; PGM = Personal Genome Machine.
Figure 2
Figure 2
High conservation across species. Multiple protein sequence alignments and the evolutionary conservation of each altered amino acid among species (H. sapiens, P. troglodytes, M. mulatta, C. lupus, and B. taurus).
Figure 3
Figure 3
Atrial fibrillation disease genes. A schematic of proteins encoded by genes related to atrial fibrillation and their subcellular localization. Proteins participate in many diverse biological processes of cardiomyocytes/fibroblasts.
Figure 4
Figure 4
AKAP9 is required for myonuclear positioning in C2C12 myotubes. (a) Representative immunofluorescence images of control (no transfection and Scramble siRNA treated cells) or AKAP9-depleted C2C12 myotubes (using 3 individual siRNA, 30 nM each) differentiated for 5 days and immunostained for myosin heavy chain (green) and 49,6-diamidino-2-phenylindole (red). Scale bar, 160 um. (b) 7× magnifications of rectangles shown in images (a). Scale bar, 160 um. (c) Histogram of percentage of total C2C12 myotubes with aggregated nuclei control (no transfection and Scramble siRNA treated cells) or AKAP9-depleted C2C12 myotubes (using 3 individual siRNA, 30 nM each) differentiated for 5 days. Center lines show the medians; box limits indicate the 25th and 75th percentiles as determined by R software; whiskers extend to 5th and 95th percentiles, outliers are represented by dots; width of the boxes is proportional to the square root of the sample size; data points are plotted as open circles. n = 6, 12, 9, 9, 7 sample points. Student's t-tests were performed between scrambled siRNA and experimental condition. Asterisk, P, 0.05; two asterisks, P, 0.01; ns: nonsignificant.
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References

    1. Chugh S. S., Havmoeller R., Narayanan K., et al. Worldwide epidemiology of atrial fibrillation: a global burden of disease 2010 study. Circulation. 2014;129(8):837–847. doi: 10.1161/circulationaha.113.005119. - DOI - PMC - PubMed
    1. Kirchhof P., Lip G. Y. H., Van Gelder I. C., et al. Comprehensive risk reduction in patients with atrial fibrillation: Emerging diagnostic and therapeutic options—a report from the 3rd Atrial Fibrillation Competence NETwork/European Heart Rhythm Association consensus conference. Europace. 2012;14(1):8–27. doi: 10.1093/europace/eur241. - DOI - PMC - PubMed
    1. Nattel S., Burstein B., Dobrev D. Atrial remodeling and atrial fibrillation: mechanisms and implications. Circulation: Arrhythmia and Electrophysiology. 2008;1(1):62–73. doi: 10.1161/CIRCEP.107.754564. - DOI - PubMed
    1. Chen P.-S., Chen L. S., Fishbein M. C., Lin S.-F., Nattel S. Role of the autonomic nervous system in atrial fibrillation: pathophysiology and therapy. Circulation Research. 2014;114(9):1500–1515. doi: 10.1161/CIRCRESAHA.114.303772. - DOI - PMC - PubMed
    1. Fox C. S., Parise H., D'Agostino R. B., et al. Parental atrial fibrillation as a risk factor for atrial fibrillation in offspring. Journal of the American Medical Association. 2004;291(23):2851–2855. doi: 10.1001/jama.291.23.2851. - DOI - PubMed