Association of mitochondrial DNA C7028T, G3010A, G9055A polymorphisms and the severity of chronic heart failure of ischemic genesis
https://doi.org/10.29001/2073-8552-2025-40-4-123-130
Abstract
Introduction. Common mitochondrial DNA (mtDNA) polymorphisms can affect the intensity of cellular respiration and the production of reactive oxygen species. Excessive amounts of reactive oxygen species lead to oxidative stress, which contributes to the development of multifactorial diseases. It can be expected that mtDNA polymorphisms can act as candidate risk loci for the development or progression of cardiovascular pathology.
Aim: To evaluate the association of mtDNA polymorphisms C7028T, G3010A and G9055A with the severity of chronic heart failure (CHF) in patients with ischemic heart disease.
Material and Methods. The sample included 97 patients aged 63 (58; 68) years. A history of myocardial infarction was diagnosed in 74 (76.3%) patients. Standard clinical and instrumental research methods were performed. The mtDNA polymorphisms were determined using polymerase chain reaction followed by restriction fragment length polymorphism analysis.
Results. It was found that among patients with a moderately reduced ejection fraction, the 7028T allele was found 2 times more often than among patients with preserved and reduced ejection fraction (EF) (78.9% versus 34.3% and 34.9%, p = 0.002). In patients with low EF and right atrial dilation, the frequency of the 7028C allele was 8 (44.4%), the 7028T allele – 10 (55.6%); without dilation – 20 (80.0%) and 5 (20.0%) (p = 0.024). There was no association between the G3010A polymorphism and parameters characterizing the severity of CHF. However, the frequency of 3010A substitution was lower among patients requiring diuretic therapy than among those not taking diuretics (8.6% vs. 30.8%, p = 0.005). Only 3 patients (3.1%) were identified with the 9055A allele.
Conclusion. Among patients with CHF of ischemic genesis, an association of mtDNA C7028T polymorphism with a heart failure phenotype with a moderately reduced left ventricular EF and in group with low EF with right atrial dilation was revealed. The mtDNA G3010A polymorphism was associated with a diuretic prescription.
Keywords
About the Authors
E. F. MuslimovaРоссия
Elvira F. Muslimova - Cand. Sci. (Med.), Research Scientist, Laboratory of Molecular and Cellular Pathology and Gene Diagnostics, Cardiology Research Institute, Tomsk NRMC.
634012, Tomsk, Kievskaya str., 111a
E. A. Kuzheleva
Россия
Elena A. Kuzheleva - Cand. Sci. (Med.), Senior Research Scientist, Department of Myocardial Pathology, Cardiology Research Institute, Tomsk NRMC.
634012, Tomsk, Kievskaya str., 111a
A. A. Garganeeva
Россия
Alla A. Garganeeva - Dr. Sci. (Med.), Professor, Head of the Department of Myocardial Pathology, Cardiology Research Institute, Tomsk NRMC.
634012, Tomsk, Kievskaya str., 111a
S. A. Afanasiev
Россия
Sergey A. Afanasiev - Dr. Sci. (Med.), Professor, Head of the Laboratory of Molecular and Cellular Pathology and Gene Diagnostics, Cardiology Research Institute, Tomsk NRMC.
634012, Tomsk, Kievskaya str., 111a
References
1. Wallace D.C. Mitochondria as chi. Genetics. 2008;179(2):727–735. https://doi.org/10.1534/genetics.104.91769
2. Poznyak A.V., Ivanova E.A., Sobenin I.A., Yet S.-F., Orekhov A.N. The role of mitochondria in cardiovascular diseases. Biology. 2020;9(6):137. https://doi.org/10.3390/biology9060137
3. Gori T., Münzel T. Oxidative stress and endothelial dysfunction: Therapeutic implications. Ann. Med. 2011;43(4):259–272. https://doi.org/10.3109/07853890.2010.543920
4. Mohammed S.A., Ambrosini S., Lüscher T., Paneni F., Costantino S. Epigenetic сontrol of mitochondrial function in the vasculature. Front. Cardiovasc. Med. 2020;7:28. https://doi.org/10.3389/fcvm.2020.00028
5. Li Y., Liu X. Novel insights into the role of mitochondrial fusion and fission in cardiomyocyte apoptosis induced by ischemia/reperfusion. J. Cellular Physiology. 2018;233(8):5589–5597. https://doi.org/10.1002/jcp.26522
6. Martínez-Redondo D., Marcuello A., Casajús J.A., Ara I., Dahmani Y., Montoya J. et al. Human mitochondrial haplogroup H: The highest VO2max consumer – is it a paradox? Mitochondrion. 2010;10(2):102–107. https://doi.org/10.1016/j.mito.2009.11.005
7. Golubenko M.V., Shumakova T.V., Makeeva O.A., Tarasenko N.V., Salakhov R.R., Shipulin V.M. et al. Mitochondrial DNA polymorphism and myocardial ischemia: Association of haplogroup H with heart failure. Siberian Journal of Clinical and Experimental Medicine. 2021;36(4):70–77. (In Russ.). https://doi.org/10.29001/2073-8552-2021-36-4-70-77
8. Luppi E., De Luise M., Bini C., Pelletti G., Tioli G., Kurelac I. et al. The landscape of rare mitochondrial DNA variants in sudden cardiac death: A potential role for ATP synthase. Heliyon. 2025;11(1):e41592. https://doi.org/10.1016/j.heliyon.2024.e41592
9. Ganetzky R.D., Stendel C., McCormick E.M., Zolkipli-Cunningham Z., Goldstein A.C., Klopstock T. et al. MT-ATP6 mitochondrial disease variants: Phenotypic and biochemical features analysis in 218 published cases and cohort of 14 new cases. Human Mutation. 2019;40:499–515. https://doi.org/10.1002/humu.23723
10. Heidari M.M., Khatami M., Kamalipour A., Kalantari M., Movahed M., Emmamy M.H. et al. Mitochondrial mutations in protein coding genes of respiratory chain including complexes IV, V, and mt-tRNA genes are associated risk factors for congenital heart disease. EXCLI J. 2022;21:1306–1330. https://doi.org/10.17179/excli2022-5298
11. Scheffer D.L., Garcia A.A., Lee L., Mochly-Rosen D., Ferreira J.C.B. Mitochondrial fusion, fission, and mitophagy in cardiac diseases: Challenges and therapeutic opportunities. Antioxid Redox Signal. 2022;36(13-15):844–863. https://doi.org/10.1089/ars.2021.0145
12. Domínguez-Garrido E., Martínez-Redondo D., Martín-Ruiz C., GómezDurán A., Ruiz-Pesini E., Madero P. et al. Association of mitochondrial haplogroup J and mtDNA oxidative damage in two different North Spain elderly populations. Biogerontology. 2009;10:435–442. https://doi.org/10.1007/s10522-008-9186-y
13. Wallace D.C. Bioenergetics in human evolution and disease: implications for the origins of biological complexity and the missing genetic variation of common diseases. Philos. Trans. R. Soc. Lond. B. Biol. Sci. 2013;368(1622):20120267. https://doi.org/10.1098/rstb.2012.0267
14. Atabekov T., Korepanov V., Krivolapov S., Khlynin M., Afanasiev S., Golubenko M. et al. Mitochondrial DNA polymorphisms of peripheral blood mononuclear cells associated with sustained ventricular tachycardia in patients with cardioverter-defibrillator implantation indications. Rev. Cardiovasc. Med. 2025;26(3):26744. https://doi.org/10.31083/RCM26744
15. Minasyan L., Sreekumar P.G., Hinton D.R., Kannan R. Protective mechanisms of the mitochondrial-derived peptide humanin in oxidative and endoplasmic reticulum stress in RPE cells. Oxid. Med. Cell Longev. 2017;2017:1675230. https://doi.org/10.1155/2017/1675230
16. Cobb L.J., Lee C., Xiao J., Yen K., Wong R.G., Nakamura H.K. et al. Naturally occurring mitochondrial-derived peptides are age-dependent regulators of apoptosis, insulin sensitivity, and inflammatory markers. Aging (Albany NY). 2016;8(4):796–809. https://doi.org/10.18632/aging.100943
17. Bai R-K., Leal S.M., Covarrubias D., Liu A., Wong L.-J.C. Mitochondrial genetic background modifies breast cancer risk. Cancer Res. 2007;67(10):4687–4694. https://doi.org/10.1158/0008-5472.CAN-06-3554
18. Castañeda V., Haro-Vinueza A., Salinas I., Caicedo A., Méndez M.Á. The MitoAging Project: Single nucleotide polymorphisms (SNPs) in mitochondrial genes and their association to longevity. Mitochondrion. 2022;66:13–26. https://doi.org/10.1016/j.mito.2022.06.008
19. Shlyakhtina N.V., Antonenok E.A., Galantsev A.O. Clinical and pathogenetic features of chronic heart failure with mid-range ejection fraction. Siberian Journal of Clinical and Experimental Medicine. 2021;36(3):45–50. (In Russ.). https://doi.org/10.29001/2073-8552-2021-36-3-45-50
20. Kirichenko T.V., Sobenin I.A., Khasanova Z.B., Orekhova V.A., Melnichenko A.A., Demakova N.A. et al. Data on association of mitochondrial heteroplasmy and cardiovascular risk factors: Comparison of samples from Russian and Mexican populations. Data in Brief. 2018;18:16–21. https://doi.org/10.1016/j.dib.2018.02.068
Review
For citations:
Muslimova E.F., Kuzheleva E.A., Garganeeva A.A., Afanasiev S.A. Association of mitochondrial DNA C7028T, G3010A, G9055A polymorphisms and the severity of chronic heart failure of ischemic genesis. Siberian Journal of Clinical and Experimental Medicine. 2025;40(4):123-130. (In Russ.) https://doi.org/10.29001/2073-8552-2025-40-4-123-130
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