Role of Mitochondrial Genome Mutations in Pathogenesis of Carotid Atherosclerosis.

Margarita A Sazonova,Elena I Yarygina,Zukhra B Khasanova,Igor A Sobenin,Vasily V Sinyov,Elena V Galitsyna,Anastasia I Ryzhkova,Anton Yu Postnov,Alexander N Orekhov

doi:10.1155/2017/6934394

Abstract

Mutations of mtDNA, due to their higher frequency of occurrence compared to nuclear DNA mutations, are the most promising biomarkers for assessing predisposition of the occurrence and development of atherogenesis. The aim of the present article was an analysis of correlation of several mitochondrial genome mutations with carotid atherosclerosis. Leukocytes from blood of study participants from Moscow polyclinics were used as research material. The sample size was 700 people. The sample members were diagnosed with “atherosclerosis” on the basis of ultrasonographic examination and biochemical and molecular cell tests. DNA was isolated from blood leukocyte samples of the study participants. PCR fragments of DNA, containing the region of 11 investigated mutations, were pyrosequenced. The heteroplasmy level of these mutations was detected. Statistical analysis of the obtained results was performed using the software package SPSS 22.0. According to the obtained results, an association of mutations m.652delG, m.3336C>T, m.12315G>A, m.14459G>A m.15059G>A with carotid atherosclerosis was found. These mutations can be biomarkers for assessing predisposition to this disease. Additionally, two single nucleotide substitutions (m.13513G>A and m.14846G>A), negatively correlating with atherosclerotic lesions, were detected. These mutations may be potential candidates for gene therapy of atherosclerosis and its risk factors.

Highlights

More and more attention is paid to molecular genetic diagnostics of polygenic multifactorial diseases, including cardiovascular pathologies and atherosclerosis
A search of molecular genetic markers which can be appreciated as early predictors of atherosclerosis is an important task, because it is very hard to recognize atherosclerosis by the existing “classical” clinical methods in the early stages of the disease
The importance of detecting mtDNA mutations linked with occurrence and development of atherosclerotic lesions in humans does not admit of doubt due to the fact that the mortality from atherosclerosis is at a very high level

Summary

Introduction

More and more attention is paid to molecular genetic diagnostics of polygenic multifactorial diseases, including cardiovascular pathologies and atherosclerosis. Atherosclerosis occurs in many men and women of middle age [1, 2]. Atherosclerotic lesions are occurring nowadays in a far higher percentage of young people than before. A search of molecular genetic markers which can be appreciated as early predictors of atherosclerosis is an important task, because it is very hard to recognize atherosclerosis by the existing “classical” clinical methods in the early stages of the disease. MtDNA mutations, due to their higher frequency of occurrence compared to nuclear DNA mutations, are the most promising biomarkers for assessing predisposition of the occurrence and development of atherogenesis. Each cell of a human organism, depending on the tissue, which

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