This study was undertaken to examine the association between the level of heteroplasmy for the mutation C3256T in human white blood cells and the extent of carotid atherosclerosis, as well as the presence of coronary heart disease (CHD), the major clinical manifestation of atherosclerosis. Totally, 191 participants (84 men, 107 women) aged 65.0 years (SD 9.4) were recruited in the study; 45 (24%) of them had CHD. High-resolution B-mode ultrasonography of carotids was used to estimate the extent of carotid atherosclerosis by measuring of the carotid intima-media thickness (cIMT). DNA samples were obtained from whole venous blood, and then PCR and pyrosequencing were carried out. On the basis of pyrosequencing data, the levels of C3256T heteroplasmy in DNA samples were calculated. The presence of the mutant allele was detected in all study participants; the level of C3256T heteroplasmy in white blood cells ranged from 5% to 74%. The highly significant relationship between C3256T heteroplasmy level and predisposition to atherosclerosis was revealed. In individuals with low predisposition to atherosclerosis the mean level of C3256T heteroplasmy was 16.8%, as compared to 23.8% in moderately predisposed subjects, and further to 25.2% and 28.3% in significantly and highly predisposed subjects, respectively. The level of C3256T heteroplasmy of mitochondrial genome in human white blood cells is a biomarker of mitochondrial dysfunction and risk factor for atherosclerosis; therefore, it can be used as an informative marker of genetic susceptibility to atherosclerosis, coronary heart disease and myocardial infarction.
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| http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0046573 | PLOS |
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Analysis of mitochondrial DNA heteroplasmic mutations A1555G, C3256T, T3336C, С5178А, G12315A, G13513A, G14459A, G14846А and G15059A in CHD patients with the history of myocardial infarction.
Exp Mol Pathol
February 2016
Laboratory of Angiopathology, Institute of General Pathology and Pathophysiology, Moscow, Russian Federation; Institute for Atherosclerosis Research, Skolkovo Innovative Centre, Moscow Region, Russian Federation; Department of Biophysics, Biological Faculty, Moscow State University, Moscow, Russian Federation.
The present study was undertaken in order to advance our earlier studies directed to define genetic risk of atherosclerotic vascular lesion development on a base on the analysis of sets of mutational load relevant to the mitochondrial genome mutations. A comparative evaluation of the two study participants' populations (that included coronary heart disease (CHD) patients who underwent myocardial infarction and apparently healthy donors with no clinical manifestations of coronary heart disease) on heteroplasmy levels of nine mutations of the mitochondrial genome (A1555G, C3256T, T3336C, С5178А, G12315A, G13513A, G14459A, G14846А and G15059A) that were shown previously to be associated with risk factors for atherosclerosis was performed. Close associations with the risk of cardiovascular disease were confirmed for mutation C3256T (gene MT-TL1), G12315A (gene MT-TL2), G13513A (gene MT-ND5) and G15059A (gene MT-CYB) by RT-PCR.
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Exp Mol Pathol
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Laboratory of Angiopathology, Institute of General Pathology and Pathophysiology, Moscow, Russian Federation; Institute for Atherosclerosis Research, Skolkovo Innovative Centre, Moscow Region, Russian Federation; Department of Biophysics, Biological Faculty, Moscow State University, Moscow, Russian Federation.
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Laboratory of Angiopathology, Institute of General Pathology and Pathophysiology, 8 Baltiyskaya Street, Moscow 125315, Russia ; Institute for Atherosclerosis Research, Skolkovo Innovation Centre, Moscow 121552, Russia.
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Association of mitochondrial genetic variation with carotid atherosclerosis.
PLoS One
February 2014
Russian Cardiology Research and Production Complex, Moscow, Russia.
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