October 12, 2023PLoS ONEOpen Access

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

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Why the study?

Paroxysmal atrial fibrillation can be difficult to identify before stroke occurs, prompting evaluation of genetic analysis and circulating biomarkers for risk stratification.

Do genetic risk scores and circulating biomarkers correlate with the presence of paroxysmal atrial fibrillation and history of stroke in adult patients?

Structured PICO

Do genetic risk scores and circulating biomarkers correlate with the presence of paroxysmal atrial fibrillation and history of stroke in adult patients?

Population

600 adult subjects (age ≥50 years), including 300 with paroxysmal atrial fibrillation (PAF) and 300 controls without AF, enrolled at a single center in Japan.

Intervention

Genetic risk score (GRS) using 10 single nucleotide polymorphisms (SNPs) and circulating biomarkers (cell-free DNA and 4 microRNAs)

Comparator

Control group without history of atrial fibrillation

Outcome

Association of genetic risk score and circulating biomarkers with paroxysmal atrial fibrillation and history of strokesurrogate

A genetic risk score can help assess the risk of paroxysmal atrial fibrillation, while plasma cell-free DNA levels may serve as a biomarker for a history of stroke.

Limitations

small sample size
control group might contain undiagnosed PAF patients
lack of a standardized protocol for the timing of blood sampling
cross-sectional design cannot determine causality

Implication

May aid future AF and stroke risk models but should not change practice; leaves open prospective validation.

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.