Mitochondrial DNA Polymorphisms of Peripheral Blood Mononuclear Cells Associated with Sustained Ventricular Tachycardia in Patients with Cardioverter-Defibrillator Implantation Indications
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 t...
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IMR Press
2025-03-01
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| Series: | Reviews in Cardiovascular Medicine |
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| Online Access: | https://www.imrpress.com/journal/RCM/26/3/10.31083/RCM26744 |
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| author | Tariel Atabekov Viacheslav Korepanov Sergey Krivolapov Mikhail Khlynin Sergey Afanasiev Maria Golubenko Roman Batalov Sergey Popov |
| author_facet | Tariel Atabekov Viacheslav Korepanov Sergey Krivolapov Mikhail Khlynin Sergey Afanasiev Maria Golubenko Roman Batalov Sergey Popov |
| author_sort | Tariel Atabekov |
| collection | DOAJ |
| description | 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). |
| format | Article |
| id | doaj-art-9024d3d63421405db3d1d431ab850fee |
| institution | Kabale University |
| issn | 1530-6550 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | IMR Press |
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| series | Reviews in Cardiovascular Medicine |
| spelling | doaj-art-9024d3d63421405db3d1d431ab850fee2025-08-20T03:42:25ZengIMR PressReviews in Cardiovascular Medicine1530-65502025-03-012632674410.31083/RCM26744S1530-6550(24)01720-4Mitochondrial DNA Polymorphisms of Peripheral Blood Mononuclear Cells Associated with Sustained Ventricular Tachycardia in Patients with Cardioverter-Defibrillator Implantation IndicationsTariel Atabekov0Viacheslav Korepanov1Sergey Krivolapov2Mikhail Khlynin3Sergey Afanasiev4Maria Golubenko5Roman Batalov6Sergey Popov7Department of Surgical Arrhythmology and Cardiac Pacing, Cardiology Research Institute, Tomsk National Research Medical Center, Russian Academy of Sciences, 634012 Tomsk, RussiaLaboratory of Molecular and Cellular Pathology and Gene Diagnostics, Cardiology Research Institute, Tomsk National Research Medical Center, Russian Academy of Sciences, 634012 Tomsk, RussiaDepartment of Surgical Arrhythmology and Cardiac Pacing, Cardiology Research Institute, Tomsk National Research Medical Center, Russian Academy of Sciences, 634012 Tomsk, RussiaDepartment of Surgical Arrhythmology and Cardiac Pacing, Cardiology Research Institute, Tomsk National Research Medical Center, Russian Academy of Sciences, 634012 Tomsk, RussiaLaboratory of Molecular and Cellular Pathology and Gene Diagnostics, Cardiology Research Institute, Tomsk National Research Medical Center, Russian Academy of Sciences, 634012 Tomsk, RussiaLaboratory for Population Genetics, Research Institute of Medical Genetics, Tomsk National Research Medical Center, Russian Academy of Sciences, 634050 Tomsk, RussiaDepartment of Surgical Arrhythmology and Cardiac Pacing, Cardiology Research Institute, Tomsk National Research Medical Center, Russian Academy of Sciences, 634012 Tomsk, RussiaDepartment of Surgical Arrhythmology and Cardiac Pacing, Cardiology Research Institute, Tomsk National Research Medical Center, Russian Academy of Sciences, 634012 Tomsk, RussiaBackground: 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).https://www.imrpress.com/journal/RCM/26/3/10.31083/RCM26744sustained ventricular tachycardiamitochondrial dnaperipheral blood mononuclear cellscardioverter-defibrillator |
| spellingShingle | Tariel Atabekov Viacheslav Korepanov Sergey Krivolapov Mikhail Khlynin Sergey Afanasiev Maria Golubenko Roman Batalov Sergey Popov Mitochondrial DNA Polymorphisms of Peripheral Blood Mononuclear Cells Associated with Sustained Ventricular Tachycardia in Patients with Cardioverter-Defibrillator Implantation Indications Reviews in Cardiovascular Medicine sustained ventricular tachycardia mitochondrial dna peripheral blood mononuclear cells cardioverter-defibrillator |
| title | Mitochondrial DNA Polymorphisms of Peripheral Blood Mononuclear Cells Associated with Sustained Ventricular Tachycardia in Patients with Cardioverter-Defibrillator Implantation Indications |
| title_full | Mitochondrial DNA Polymorphisms of Peripheral Blood Mononuclear Cells Associated with Sustained Ventricular Tachycardia in Patients with Cardioverter-Defibrillator Implantation Indications |
| title_fullStr | Mitochondrial DNA Polymorphisms of Peripheral Blood Mononuclear Cells Associated with Sustained Ventricular Tachycardia in Patients with Cardioverter-Defibrillator Implantation Indications |
| title_full_unstemmed | Mitochondrial DNA Polymorphisms of Peripheral Blood Mononuclear Cells Associated with Sustained Ventricular Tachycardia in Patients with Cardioverter-Defibrillator Implantation Indications |
| title_short | Mitochondrial DNA Polymorphisms of Peripheral Blood Mononuclear Cells Associated with Sustained Ventricular Tachycardia in Patients with Cardioverter-Defibrillator Implantation Indications |
| title_sort | mitochondrial dna polymorphisms of peripheral blood mononuclear cells associated with sustained ventricular tachycardia in patients with cardioverter defibrillator implantation indications |
| topic | sustained ventricular tachycardia mitochondrial dna peripheral blood mononuclear cells cardioverter-defibrillator |
| url | https://www.imrpress.com/journal/RCM/26/3/10.31083/RCM26744 |
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