Impact of Mitochondrial DNA Mutations on Carotid Intima-Media Thickness in the Novosibirsk Region
Tatiana V. Kirichenko,
Anastasia I. Ryzhkova,
Vasily V. Sinyov,
Marina D. Sazonova,
Varvara A. Orekhova,
Vasily P. Karagodin,
Elena V. Gerasimova,
Mikhail I. Voevoda,
Alexander N. Orekhov,
Yulia I. Ragino,
Igor A. Sobenin,
Margarita A. Sazonova
Affiliations
Tatiana V. Kirichenko
Laboratory of Cellular and Molecular Pathology of Cardiovascular System, Research Institute of Human Morphology, 3 Tsyurupy Str., 117418 Moscow, Russia
Anastasia I. Ryzhkova
Laboratory of Angiopathology, Institute of General Pathology and Pathophysiology, 8 Baltiyskaya Str., 125315 Moscow, Russia
Vasily V. Sinyov
Laboratory of Angiopathology, Institute of General Pathology and Pathophysiology, 8 Baltiyskaya Str., 125315 Moscow, Russia
Marina D. Sazonova
Laboratory of Angiopathology, Institute of General Pathology and Pathophysiology, 8 Baltiyskaya Str., 125315 Moscow, Russia
Varvara A. Orekhova
Laboratory of Angiopathology, Institute of General Pathology and Pathophysiology, 8 Baltiyskaya Str., 125315 Moscow, Russia
Vasily P. Karagodin
Laboratory of Angiopathology, Institute of General Pathology and Pathophysiology, 8 Baltiyskaya Str., 125315 Moscow, Russia
Elena V. Gerasimova
V.A.Nasonova Research Institute of Rheumatology, 34A Kashirskoe sh., 115522 Moscow, Russia
Mikhail I. Voevoda
Research Institute of Internal and Preventive Medicine–Branch of the Institute of Cytology and Genetics, Siberian Branch of Russian Academy of Sciences, 630089 Novosibirsk, Russia
Alexander N. Orekhov
Laboratory of Cellular and Molecular Pathology of Cardiovascular System, Research Institute of Human Morphology, 3 Tsyurupy Str., 117418 Moscow, 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, 630089 Novosibirsk, Russia
Igor A. Sobenin
Laboratory of Cellular and Molecular Pathology of Cardiovascular System, Research Institute of Human Morphology, 3 Tsyurupy Str., 117418 Moscow, Russia
Margarita A. Sazonova
Laboratory of Angiopathology, Institute of General Pathology and Pathophysiology, 8 Baltiyskaya Str., 125315 Moscow, Russia
The search for markers of predisposition to atherosclerosis development is very important for early identification of individuals with a high risk of cardiovascular disease. The aim of the present study was to investigate the association of mitochondrial DNA mutations with carotid intima-media thickness and to determine the impact of mitochondrial heteroplasmy measurements in the prognosis of atherosclerosis development. This cross-sectional, population-based study was conducted in 468 subjects from the Novosibirsk region. It was shown that the mean (carotid intima-media thickness) cIMT correlated with the following mtDNA mutations: m.15059G>A (r = 0.159, p = 0.001), m.12315G>A (r = 0.119; p = 0.011), m.5178C>A (r = 0.114, p = 0.014), and m.3256C>T (r = 0.130, p = 0.011); a negative correlation with mtDNA mutations m.14846G>A (r = −0.111, p = 0.042) and m.13513G>A (r = −0.133, p = 0.004) was observed. In the linear regression analysis, the addition of the set of mtDNA mutations to the conventional cardiovascular risk factors increased the ability to predict the cIMT variability from 17 to 27%. Multi-step linear regression analysis revealed the most important predictors of mean cIMT variability: age, systolic blood pressure, blood levels of total cholesterol, LDL and triglycerides, as well as the mtDNA mutations m.13513G>A, m.15059G>A, m.12315G>A, and m.3256C>T. Thus, a high predictive value of mtDNA mutations for cIMT variability was demonstrated. The association of mutation m.13513G>A and m.14846G>A with a low value of cIMT, demonstrated in several studies, represents a potential for the development of anti-atherosclerotic gene therapy.
