Dataset Information

Rs12976445 Polymorphism Is Associated with Post-Ablation Recurrence of Atrial Fibrillation by Modulating the Expression of MicroRNA-125a and Interleukin-6R.

ABSTRACT: BACKGROUND This study aimed to identify the relationship between miR-125a polymorphism rs12976445 and the post-ablation recurrence of atrial fibrillation (AF), as well as to explore the underlying mechanism of miR-125a in AF recurrence. MATERIAL AND METHODS Microarray analysis was performed to search for miRNAs potentially involved in the regulation of AF recurrence, while real-time PCR (polymerase chain reaction) and Western blot analyses were carried out to study the expression of miR-125a (microRNA-125a), IL-6R (interleukin-6 receptor), and IL-16 (interleukin-16) in different experimental groups, so as to understand the regulatory relationships among miR-125a, IL-6R, and IL-16. Subsequently, a logistic regression analysis was utilized to investigate the survival status of recurrent AF in subjects harboring different genotypes of rs12976445. RESULTS The subjects in the GG and GC/CC groups of miR-125a polymorphism rs12976445 showed no obvious difference regarding all demographic characteristics that were collected in this study. In addition, 19 miRNAs were identified as potentially involved in the regulation of AF recurrence. Among these miRNAs, 6 were upregulated and 13 were downregulated in the group with early recurrence. According to real-time PCR results, the expression of miR-125a was dramatically upregulated in LRAF (late recurrence of atrial fibrillation) as well as in subjects harboring the GG genotype. On the contrary, the level of IL-6R mRNA was dramatically downregulated in LRAF and subjects harboring the GG genotype. Furthermore, IL-6R was confirmed as a candidate target of miR-125a by a luciferase reporter assay. CONCLUSIONS MicroRNA-125a polymorphism rs12976445 plays a role in AF recurrence via the regulation of IL-6R.

SUBMITTER: Shen XB

PROVIDER: S-EPMC6145598 | biostudies-literature | 2018 Sep

REPOSITORIES: biostudies-literature

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Rs12976445 Polymorphism Is Associated with Post-Ablation Recurrence of Atrial Fibrillation by Modulating the Expression of MicroRNA-125a and Interleukin-6R.

Shen Xue-Bin XB Zhang Shao-Hong SH Li Hai-Yang HY Chi Xi-Di XD Jiang Ling L Huang Qi-Lei QL Xu Shang-Hua SH

Medical science monitor : international medical journal of experimental and clinical research 20180911

BACKGROUND This study aimed to identify the relationship between miR-125a polymorphism rs12976445 and the post-ablation recurrence of atrial fibrillation (AF), as well as to explore the underlying mechanism of miR-125a in AF recurrence. MATERIAL AND METHODS Microarray analysis was performed to search for miRNAs potentially involved in the regulation of AF recurrence, while real-time PCR (polymerase chain reaction) and Western blot analyses were carried out to study the expression of miR-125a (mi ...[more]

PMID: 30203815

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Project description:ObjectivesThe incidence of atrial fibrillation (AF) in patients older than 75 years of age is expected to increase, and its treatment remains challenging. This study evaluated the impact of age on the outcomes of surgical ablation of AF.MethodsA retrospective review was performed of patients who underwent the Cox-maze IV procedure at a single institution between 2005 and 2017. The patients were divided into a younger (age <75 years, n = 548) and an elderly cohort (age ≥75 years, n = 148). Rhythm outcomes were assessed at 1 year and annually thereafter. Predictors of first atrial tachyarrhythmia (ATA) recurrence were determined using Fine-Gray regression, allowing for death as the competing risk.ResultsThe mean age of the elderly group was 78.5 ± 2.8 years. The majority of patients (423/696, 61%) had nonparoxysmal AF. The elderly patients had a lower body mass index (P < .001) and greater rates of hypertension (P = .011), previous myocardial infarction (P = .017), heart failure (P < .001), and preoperative pacemaker (P = .008). Postoperatively, the elderly group had a greater rate of overall major complications (23% vs 14%, P = .017) and 30-day mortality (6% vs 2%, P = .026). The percent freedom from ATAs and antiarrhythmic drugs was lower in the elderly patients at 3 (69% vs 82%, P = .030) and 4 years (65% vs 79%, P = .043). By competing risk analysis, the incidence of first ATA recurrence was greater in elderly patients (33% vs 20% at 5 years; Gray test, P = .005). On Fine-Gray regression adjusted for clinically relevant covariates, increasing age was identified as a predictor of ATAs recurrence (subdistribution hazard ratio, 1.03; 95% confidence interval, 1.02-1.05, P < .001).ConclusionsThe efficacy of the Cox-maze IV procedure was worse in elderly patients; however, the majority of patients remained free of ATAs at 5 years. The lower success rate in these greater-risk patients should be considered when deciding to perform surgical ablation.

Project description:BackgroundLeft atrial (LA) function following catheter or surgical ablation of de-novo long-standing persistent atrial fibrillation (AF) and its impact on AF recurrence was studied in patients participating in the CASA-AF trial (Catheter Ablation vs. Thoracoscopic Surgical Ablation in Long Standing Persistent Atrial Fibrillation).MethodsAll patients underwent echocardiography preablation, 3 and 12 months post-ablation. LA structure and function were assessed by 2-dimensional volume and speckle tracking strain measurements of LA reservoir, conduit, and contractile strain. Left ventricular diastolic function was measured using transmitral Doppler filling velocities and myocardial tissue Doppler velocities to derive the e', E/e', and E/A ratios. Continuous rhythm monitoring was achieved using an implantable loop recorder.ResultsEighty-three patients had echocardiographic data suitable for analysis. Their mean age was 63.6±9.7 years, 73.5% were male, had AF for 22.8±11.6 months, and had a mean LA maximum volume of 48.8±13.8 mL/m2. Thirty patients maintained sinus rhythm, and 53 developed AF recurrence. Ablation led to similar reductions in LA volumes at follow-up in both rhythm groups. However, higher LA emptying fraction (36.3±10.6% versus 27.9±9.9%; P<0.001), reservoir strain (22.6±8.5% versus 16.7±5.7%; P=0.001), and contractile strain (9.2±3.4% versus 5.6±2.5%; P<0.001) were noted in the sinus rhythm compared with AF recurrence group following ablation at 3 months. Diastolic function was better in the sinus rhythm compared with the AF recurrence group with an E/A ratio of 1.5±0.5 versus 2.2±1.2 (P<0.001) and left ventricular E/e' ratio of 8.0±2.1 versus 10.3±4.1 (P<0.001), respectively. LA contractile strain at 3 months was the only independent predictor of AF recurrence.ConclusionsFollowing ablation for long-standing persistent AF, improvement in LA function was greater in those who maintained sinus rhythm. LA contractile strain at 3 months was the most important determinant of AF recurrence following ablation.RegistrationURL: https://www.Clinicaltrialsgov; Unique identifier: NCT02755688.

Project description:BackgroundRecurrence after atrial fibrillation (AF) ablation remains common. We evaluated the association between recurrence and levels of biomarkers of cardiac remodeling, and their ability to improve recurrence prediction when added to a clinical prediction model.Methods and resultsBlood samples collected before de novo catheter ablation were analyzed. Levels of bone morphogenetic protein-10, angiopoietin-2, fibroblast growth factor-23, insulin-like growth factor-binding protein-7, myosin-binding protein C3, growth differentiation factor-15, interleukin-6, N-terminal pro-brain natriuretic peptide, and high-sensitivity troponin T were measured. Recurrence was defined as ≥30 seconds of an atrial arrhythmia 3 to 12 months postablation. Multivariable logistic regression was performed using biomarker levels along with clinical covariates: APPLE score (Age >65 years, Persistent AF, imPaired eGFR [<60 ml/min/1.73m2], LA diameter ≥43 mm, EF <50%; which includes age, left atrial diameter, left ventricular ejection fraction, persistent atrial fibrillation, and estimated glomerular filtration rate), preablation rhythm, sex, height, body mass index, presence of an implanted continuous monitor, year of ablation, and additional linear ablation. A total of 1873 participants were included. A multivariable logistic regression showed an association between recurrence and levels of angiopoietin-2 (odds ratio, 1.08 [95% CI, 1.02-1.15], P=0.007) and interleukin-6 (odds ratio, 1.02 [95% CI, 1.003-1.03]; P=0.02). The area under the receiver operating characteristic curve of a model that only contained clinical predictors was 0.711. The addition of any of the 9 studied biomarkers to the predictive model did not result in a statistically significant improvement in the area under the receiver operating characteristic curve.ConclusionsHigher angiopoietin-2 and interleukin-6 levels were associated with recurrence after atrial fibrillation ablation in multivariable modeling. However, the addition of biomarkers to a clinical prediction model did not significantly improve recurrence prediction.

Dataset Information

Rs12976445 Polymorphism Is Associated with Post-Ablation Recurrence of Atrial Fibrillation by Modulating the Expression of MicroRNA-125a and Interleukin-6R.

Publications

Rs12976445 Polymorphism Is Associated with Post-Ablation Recurrence of Atrial Fibrillation by Modulating the Expression of MicroRNA-125a and Interleukin-6R.

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