New markers of atherosclerosis: a threshold level of heteroplasmy in mtDNA mutations

Aim: The aim of the present article was the detection of threshold heteroplasmy level of mitochondrial DNA mutations, above which a patient is at increased risk of atherosclerotic lesions. Besides, this parameter was detected for mutations, in which after reaching threshold heteroplasmy level, a protective antiatherogenic effect started to appear.Methods: The participants of the study were 700 women and men from the Moscow region. Fragments of DNA, amplified by polymerase chain reaction, were analyzed with pyrosequencing technology. Then on the basis of pyrograms’ peaks in the samples, the heteroplasmy level of the investigated mitochondrial genome mutations was detected.Results: The threshold heteroplasmy level of 11 investigated mutations (m.5178C>A, m.15059G>A, m.652delG, m.13513G>A, m.14846G>A, m.652insG, m.12315G>A, m.3336T>C, m.1555A>G, m.14459G>A, m.3256C>T) in individuals with atherosclerotic plaques or thickening of the intima-medial layer of carotid arteries was detected.Conclusion: Using the method developed in our laboratory, the authors managed to determine threshold heteroplasmy levels of 11 mitochondrial genome mutations associated with atherosclerosis. The authors suggest that threshold heteroplasmy levels of these mutations is a new criterion for evaluation of predisposition to the occurrence and development of atherosclerotic lesions in human arteries