Analysis of the heteroplasmy level of the mitochondrial genome G15059A mutation of the CYTB gene in lipofibrous plaques of the human aortic intima

Abstract

Target. Mitochondrial mutations are associated with certain human pathologies. Their penetrance and expressiveness depends on the level of heteroplasmy. Therefore, when studying the association of mitochondrial mutations with human diseases, it is necessary to quantify the mutant allele of the mitochondrial genome. The aim of this study was a pilot analysis of the heteroplasmy level of the m.C15059A mutation of the CYTV gene (MT-CYB) in lipofibrous plaques and normal intima of the human aorta. As is known from the literature, this mutation is associated with mitochondrial myopathy, myoglobinuria, arterial hypertension and some other human pathologies. Material and methods. The material for the study was tissue samples from the aortic intima of seven persons who died in an accident or sudden death. Normal aortic intima was compared with lipofibrous plaques. The DNA amplifications containing the region of the mutation under study were analyzed by an original method for quantifying the mutant allele of the mitochondrial genome based on pyrosequencing technology. Statistical processing of the results was carried out using bootstrap analysis. Results. According to the data obtained, the level of heteroplasmy of the mitochondrial genome mutation m. C15059A was significantly higher in lipofibrous plaques compared to normal vascular tissue in 43% of aortas. In the rest of the analyzed aortas, the level of heteroplasmy of this mutation in the normal and atherosclerotic intima of the aorta was approximately the same. Correlation analysis, carried out by the bootstrap method, showed that the mutation m.С15059А is associated with lipofibrous plaque of the aorta at a significance level of p≤0.0 5. Due to the fact that m.С15059А is a nonsense mutation causing the formation of a stop codon, in As a result of which there is a loss of 244 amino acid residues of cytochrome B, it can be assumed that this genetic defect in the respiratory chain enzyme can cause oxidative stress in the aortic intima, leading to the local occurrence of atherosclerotic lesions in humans. Conclusion. In the present study, it was found that the somatic mutation of the mitochondrial genome m. C15059A, localized in the gene encoding cytochrome B, is associated with lipofibrous plaques of the human aortic intima. This information can be useful to scientists specializing in the study of atherogenesis.