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. 2023 Oct 12;18(10):e0292118.
doi: 10.1371/journal.pone.0292118. eCollection 2023.

Risk stratification of atrial fibrillation and stroke using single nucleotide polymorphism and circulating biomarkers

Tetsuo Sasano  1 , Kensuke Ihara  2 , Toshihiro Tanaka  3   4 , Tetsushi Furukawa  2
Affiliations

Risk stratification of atrial fibrillation and stroke using single nucleotide polymorphism and circulating biomarkers

Tetsuo Sasano et al. PLoS One. .

Abstract

Background: Atrial fibrillation (AF) is the most common sustained arrhythmia, and it causes a high rate of complications such as stroke. It is known that AF begins as paroxysmal form and gradually progresses to persistent form, and sometimes it is difficult to identify paroxysmal AF (PAF) before having stroke. The aim of this study is to evaluate the risk of PAF and stroke using genetic analysis and circulating biomarkers.

Materials and methods: A total of 600 adult subjects were enrolled (300 from PAF and control groups). Peripheral blood was drawn to identify the genetic variation and biomarkers. Ten single nucleotide polymorphisms (SNPs) were analyzed, and circulating cell-free DNA (cfDNA) was measured from plasma. Four microRNAs (miR-99a-5p, miR-192-5p, miR-214-3p, and miR-342-5p) were quantified in serum using quantitative RT-PCR.

Results: Genotyping identified 4 single nucleotide polymorphisms (SNPs) that were significantly associated with AF (rs6817105, rs3807989, rs10824026, and rs2106261), and the genetic risk score using 4 SNPs showed the area under the curve (AUC) of 0.631. Circulating miRNAs and cfDNA did not show significant differences between PAF and control groups. The concentration of cfDNA was significantly higher in patients with a history of stroke, and the AUC was 0.950 to estimate the association with stroke.

Conclusion: The risk of AF could be assessed by genetic risk score. Furthermore, the risk of stroke might be evaluated by plasma cfDNA level.

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Conflict of interest statement

NO authors have competing interests.

Figures

Fig 1
Fig 1. Association between atrial fibrillation and genetic risk score.
ROC curves using GRS-1 (A) and GRS-2 (B) are shown.
Fig 2
Fig 2. Expression level of biomarkers.
(A) Cell-free DNA levels in plasma were higher in PAF group but did not reach to statistical significance. (B) Four previously reported miRNA was measured from the serum sample. All of them did not show statistical significance between PAF and control group.
Fig 3
Fig 3. Plasma cell-free DNA level as a biomarker to estimate subjects with stroke.
(A) The cfDNA levels were significantly larger in the stroke group than the control. (B) ROC curve analysis to estimate subjects with stroke. * p<0.01.
Fig 4
Fig 4. Risk assessment for stroke using clinical information, genes, and biomarker.
(A) ROC curve analysis to estimate stroke group by CHADS2 score in PAF group. (B) ROC curve analysis to estimate stroke group by combining CHADS2 score, genetic risk score, and cfDNA score.
See this image and copyright information in PMC

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References

    1. Escudero-Martínez I, Morales-Caba L, Segura T. Atrial fibrillation and stroke: A review and new insights. Trends Cardiovasc Med. 2023;33(1):23–9. doi: 10.1016/j.tcm.2021.12.001 - DOI - PubMed
    1. Kirchhof P, Camm AJ, Goette A, Brandes A, Eckardt L, Elvan A, et al. Early Rhythm-Control Therapy in Patients with Atrial Fibrillation. N Engl J Med. 2020;383(14):1305–16. doi: 10.1056/NEJMoa2019422 . - DOI - PubMed
    1. Ellinor PT, Lunetta KL, Albert CM, Glazer NL, Ritchie MD, Smith AV, et al. Meta-analysis identifies six new susceptibility loci for atrial fibrillation. Nat Genet. 2012;44(6):670–5. doi: 10.1038/ng.2261 - DOI - PMC - PubMed
    1. Christophersen IE, Rienstra M, Roselli C, Yin X, Geelhoed B, Barnard J, et al. Large-scale analyses of common and rare variants identify 12 new loci associated with atrial fibrillation. Nat Genet. 2017;49(6):946–52. doi: 10.1038/ng.3843 - DOI - PMC - PubMed
    1. Liu L, Ebana Y, Nitta J-i, Takahashi Y, Miyazaki S, Tanaka T, et al. Genetic Variants Associated With Susceptibility to Atrial Fibrillation in a Japanese Population. Can J Cardiol. 2017;33(4):443–9. doi: 10.1016/j.cjca.2016.10.029 - DOI - PubMed

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