Сравнительный анал из гетероплазмии митохондриальной ДНК в лейкоцитах крови и атероклеротически пораженных сосудах

Abstract

Mitochondrial DNA (mtDNA) is exposed to reactive oxygen species in mitochondria, and oxidative stress is important factor in atherosclerosis development. Oxidative damage leads to somatic mtDNA mutations which can persist in cell in heteroplasmic state. The aim of the study was to analyze mtDNA heteroplasmy in carotid atherosclerotic lesions and leucocytes of patients with atherosclerosis (n = 22) and healthy individuals (n = 14). Heteroplasmy was estimated using massive parallel sequencing technology (MiSeq, Illumina). The results of the study show that mtDNA heteroplasmy is abundant phenomenon in both patients and controls (altogether 143 heteroplasmic positions at level >1.5%). However, mean level of mutant molecules was low (<10%). The highest frequency of somatic mutations was registered in noncoding regions, and the lowest frequency was in protein-coding genes. In some positions, recurrent mutations have been found. Among them, heteroplasmy in 16390 position was found only in atherosclerotic plaques, so it can be tissue-specific. In addition, we found heteroplasmy in position 166 in most samples, with mean level in patients higher than in controls.