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.

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.

Mutations of mitochondrial DNA in atherosclerosis and atherosclerosis-related diseases.

Atherosclerosis, the primary cause of cardiovascular disease, is a complex and multifactorial pathology resulted from the harmful interactions between genetic and environmental factors. There is a growing body of evidence in support of the role of mitochondrial factors in the pathogenesis of atherosclerosis. Impaired mitochondrial function and structural and qualitative changes in mitochondrial components such as mitochondrial DNA (mtDNA) damage may be directly involved in the development of multiple mechanisms of atherogenesis.

Quantitative assessment of heteroplasmy of mitochondrial genome: perspectives in diagnostics and methodological pitfalls.

The role of alterations of mitochondrial DNA (mtDNA) in the development of human pathologies is not understood well. Most of mitochondrial mutations are characterized by the phenomenon of heteroplasmy which is defined as the presence of a mixture of more than one type of an organellar genome within a cell or tissue. The level of heteroplasmy varies in wide range, and the expression of disease is dependent on the percent of alleles bearing mutations, thus allowing consumption that an upper threshold level may exist beyond which the mitochondrial function collapses.