Variability of Mitochondrial DNA Heteroplasmy: Association with Asymptomatic Carotid Atherosclerosis
Margarita A. Sazonova,
Tatiana V. Kirichenko,
Anastasia I. Ryzhkova,
Marina D. Sazonova,
Natalya A. Doroschuk,
Andrey V. Omelchenko,
Nikita G. Nikiforov,
Yulia I. Ragino,
Anton Yu. Postnov
Affiliations
Margarita A. Sazonova
Laboratory of Angiopathology, Institute of General Pathology and Pathophysiology, 8 Baltiiskaya Street, Moscow 125315, Russia
Tatiana V. Kirichenko
Laboratory of Cellular and Molecular Pathology of Cardiovascular System, Federal State Budgetary Scientific Institution, Petrovsky National Research Centre of Surgery (FSBSI “Petrovsky NRCS”), Moscow 117418, Russia
Anastasia I. Ryzhkova
Laboratory of Angiopathology, Institute of General Pathology and Pathophysiology, 8 Baltiiskaya Street, Moscow 125315, Russia
Marina D. Sazonova
Laboratory of Angiopathology, Institute of General Pathology and Pathophysiology, 8 Baltiiskaya Street, Moscow 125315, Russia
Natalya A. Doroschuk
Laboratory of Angiopathology, Institute of General Pathology and Pathophysiology, 8 Baltiiskaya Street, Moscow 125315, Russia
Andrey V. Omelchenko
Laboratory of Angiopathology, Institute of General Pathology and Pathophysiology, 8 Baltiiskaya Street, Moscow 125315, Russia
Nikita G. Nikiforov
Laboratory of Cellular and Molecular Pathology of Cardiovascular System, Federal State Budgetary Scientific Institution, Petrovsky National Research Centre of Surgery (FSBSI “Petrovsky NRCS”), Moscow 117418, Russia
Yulia I. Ragino
Research Institute of Internal and Preventive Medicine—Branch of the Institute of Cytology and Genetics, Siberian Branch of Russian Academy of Sciences, Novosibirsk 630089, Russia
Anton Yu. Postnov
Laboratory of Medical Genetics, Institute of Experimental Cardiology, Chazov National Medical Research Center of Cardiology, 15a, 3rd Cherepkovskaya Str., Moscow 121552, Russia
Background and Objectives: Atherosclerosis is one of the main reasons for cardiovascular disease development. This study aimed to analyze the association of mtDNA mutations and atherosclerotic plaques in carotid arteries of patients with atherosclerosis and conditionally healthy study participants from the Novosibirsk region. Methods: PCR fragments of DNA containing the regions of 10 investigated mtDNA mutations were pyrosequenced. The heteroplasmy levels of mtDNA mutations were analyzed using a quantitative method based on pyrosequencing technology developed by M. A. Sazonova and colleagues. Results: In the analysis of samples of patients with atherosclerotic plaques of the carotid arteries and conditionally healthy study participants from the Novosibirsk region, four proatherogenic mutations in the mitochondrial genome (m.5178C>A, m.652delG, m.12315G>A and m.3256C>T) and three antiatherogenic mutations in mtDNA (m.13513G>A, m.652insG, and m.14846G>A) were detected. A west–east gradient was found in the distribution of the mtDNA mutations m.5178C>A, m.3256C>T, m.652insG, and m.13513G>A. Conclusions: Therefore, four proatherogenic mutations in the mitochondrial genome (m.5178C>A, m.652delG, m.12315G>A, and m.3256C>T) and three antiatherogenic mutations in mtDNA (m.13513G>A, m.652insG, and m.14846G>A) were detected in patients with atherosclerotic plaques in their carotid arteries from the Novosibirsk region.
