Mitochondrial DNA Polymorphisms of Peripheral Blood Mononuclear Cells Associated with Sustained Ventricular Tachycardia in Patients with Cardioverter-Defibrillator Implantation Indications.

IF 1.9 4区医学 Q3 CARDIAC & CARDIOVASCULAR SYSTEMS

Reviews in cardiovascular medicine Pub Date : 2025-03-17 eCollection Date: 2025-03-01 DOI:10.31083/RCM26744

Tariel Atabekov, Viacheslav Korepanov, Sergey Krivolapov, Mikhail Khlynin, Sergey Afanasiev, Maria Golubenko, Roman Batalov, Sergey Popov

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引用次数: 0

Abstract

Background: Mitochondrial dysfunction in myocardium cells has been implicated in arrhythmogenesis, including ventricular tachycardia (VT). A carriage of point mitochondrial DNA (mtDNA) polymorphisms may contribute to the risk of certain arrhythmias. Therefore, it is hypothesized that mtDNA genotype could predict the risk of sustained VT (_SVT). We aimed to explore whether specific mtDNA polymorphisms of peripheral blood mononuclear cells (PBMC) can serve as biomarkers for predicting the risk of _SVT in patients with indications for an implantable cardioverter-defibrillator (ICD).

Methods: A total of 122 patients with ICD implantation indications who underwent transthoracic echocardiography (TTE) were enrolled in the study. Total DNA from PBMC was isolated using the phenol-chloroform extraction method. Genotyping of mtDNA polymorphisms A2706G, G3010A and G9055A was performed using restriction fragment length polymorphism analysis. Correlations between clinical parameters and mtDNA polymorphisms with _SVT registered prior to ICD implantation were evaluated. Based on our data, we developed a risk model for _SVT.

Results: Prior to ICD implantation, 70 (56.6%) patients had _SVT (1st group) and 52 (43.4%) patients did not have _SVT (2nd group). Patients with _SVT were significantly older than patients without _SVT (66.9 ± 9.9 year vs. 59.5 ± 10.6 year, p < 0.001), had a lower value estimated glomerular filtration rate (_eGFR) (65.7 ± 19.7 mL/min/1.73 m² vs. 77.9 ± 16.1 mL/min/1.73 m², p < 0.001) and less frequently had A2706G mtDNA polymorphism (55.7% vs. 76.9%, p = 0.015). According to the multivariable logistic regression, age (odds ratio (OR) = 1.055, 95% confidence interval (CI) 1.009-1.103, p = 0.017), _eGFR (OR = 0.974, 95% CI 0.949-0.999, p = 0.041) and absence of A2706G mtDNA polymorphism (OR = 0.335, 95% CI 0.141-0.797, p = 0.013) were independently associated with the _SVT. We constructed a logistic equation with calculation of the cut-off value. The discriminative ability of the receiver operating characteristic curve (area under the curve) was 0.761 (95% confidence interval 0.675-0.833; sensitivity 65.71%; specificity 76.92%).

Conclusions: In patients with ICD implantation indications, a carriage of mtDNA polymorphism A2706G is associated with _SVT. Our risk model including age, _eGFR and absence of A2706G mtDNA substitution was able to distinguish patients with _SVT. Further investigations of their predictive significance are warranted.

Clinical trial registration: NCT03667989 (https://clinicaltrials.gov/study/NCT03667989).

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伴有心律转复除颤器植入适应症的患者外周血单个核细胞线粒体DNA多态性与持续性室性心动过速相关。

背景：心肌细胞线粒体功能障碍与心律失常有关，包括室性心动过速（VT）。携带点线粒体DNA （mtDNA）多态性可能会增加某些心律失常的风险。因此，我们假设mtDNA基因型可以预测持续性VT （SVT）的风险。我们的目的是探讨外周血单个核细胞（PBMC）特异性mtDNA多态性是否可以作为预测有植入式心律转复除颤器（ICD）适应症患者SVT风险的生物标志物。方法：对122例有ICD植入指征的经胸超声心动图（TTE）患者进行研究。采用苯酚-氯仿萃取法分离PBMC的总DNA。采用限制性内切片段长度多态性分析对mtDNA多态性A2706G、G3010A和G9055A进行基因分型。评估ICD植入前登记的SVT与临床参数和mtDNA多态性之间的相关性。基于我们的数据，我们开发了SVT的风险模型。结果：ICD植入前，有SVT 70例（56.6%）（第一组），无SVT 52例（43.4%）（第二组）。有SVT的患者明显比没有SVT的患者年龄大（66.9±9.9岁比59.5±10.6岁，p < 0.001），肾小球滤过率（eGFR）估计值较低（65.7±19.7 mL/min/1.73 m2比77.9±16.1 mL/min/1.73 m2, p < 0.001）， A2706G mtDNA多态性较少（55.7%比76.9%,p = 0.015）。根据多变量logistic回归分析，年龄(优势比（OR) = 1.055, 95%可信区间（CI） 1.009 ~ 1.103, p = 0.017）、eGFR （OR = 0.974, 95% CI 0.949 ~ 0.999, p = 0.041）和是否存在A2706G mtDNA多态性（OR = 0.335, 95% CI 0.141 ~ 0.797, p = 0.013）与SVT独立相关。我们构造了一个逻辑方程，并计算了临界值。受试者工作特征曲线（曲线下面积）的判别能力为0.761(95%置信区间0.675 ~ 0.833；灵敏度65.71%;特异性76.92%)。结论：在有ICD植入指征的患者中，携带mtDNA多态性A2706G与SVT相关。我们的风险模型包括年龄、eGFR和缺乏A2706G mtDNA替代，能够区分SVT患者。对其预测意义的进一步研究是有必要的。临床试验注册：NCT03667989 （https://clinicaltrials.gov/study/NCT03667989）。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Reviews in cardiovascular medicine 医学-心血管系统

CiteScore

2.70

自引率

3.70%

发文量

377

审稿时长

1 months

期刊介绍： RCM is an international, peer-reviewed, open access journal. RCM publishes research articles, review papers and short communications on cardiovascular medicine as well as research on cardiovascular disease. We aim to provide a forum for publishing papers which explore the pathogenesis and promote the progression of cardiac and vascular diseases. We also seek to establish an interdisciplinary platform, focusing on translational issues, to facilitate the advancement of research, clinical treatment and diagnostic procedures. Heart surgery, cardiovascular imaging, risk factors and various clinical cardiac & vascular research will be considered.