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Page 2 of 10 Sobenin et al. Vessel Plus 2019;3:14 I http://dx.doi.org/10.20517/2574-1209.2018.63

pressure; m.14846G>A-with fasting glucose). There was no correlation between integral severity of MetS and cIMT.

Conclusion: In this study, the MetS phenotype was not explained directly by atherosclerosis-related mtDNA variants. It
is possible to hypothesize that mtDNA-related mechanisms in atherosclerosis and MetS may be different, in spite of the
similarity of several phenotypic characteristics.

Keywords: Metabolic syndrome, carotid atherosclerosis, mitochondrial DNA mutations, risk factors

INTRODUCTION
Excessive body mass, obesity, metabolic syndrome (MetS) and Type 2 diabetes are metabolic disturbances
affecting the population, often occurring in parallel with atherosclerosis development, contributing
to morbidity. All of these pathologies are characterized by excessive deposition of body fat and health
impairment. Cardiovascular and metabolic diseases are in part of genetic, in part of behavioral origin.
Genetic influences are either hereditary or due to somatic (acquired) mutations. Pathogenic mutations
can occur either in the nuclear DNA or in the mitochondrial DNA (mtDNA). A number of genome-wide
[1-4]
association studies (GWAS) have been carried out in order to discover genes related to metabolic diseases .
However, commercially available GWAS arrays used in such studies rarely cover mitochondrial variants
in the population very well. Therefore, the role of mitochondrial genes in metabolic diseases has been less
well studied, even though the mitochondria play the definitive role in energy production and metabolism,
and in the development of oxidative stress. Despite the ever increasing prevalence and high heritability of
atherosclerosis and metabolic diseases, as well as intensive and long research efforts, the causal genes remain
poorly known. Mitochondria are the center of energy metabolism in the human body; therefore, variations
of their genes and function are expected to influence metabolism and reactive oxygen species (ROS)
production.

Epidemiological and clinical studies have revealed a clustering of conventional cardiovascular risk
factors including obesity, MetS, Type 2 diabetes mellitus, atherosclerosis, and coronary artery disease.
Each conventional risk factor alone increases the risk of clinical manifestations of atherosclerosis with
the combination of several risk factors exacerbating clinical sequelae. This is also true in the setting
of MetS, with multiple risk factors resulting in heightened risk of atherosclerotic disease together with
cardiometabolic abnormalities. MetS is also generally defined in clinical studies and clinical practice as a
cluster of risk factors associated with Type 2 diabetes mellitus and cardiovascular disease [5-10] . It is further
generally recognized that conventional risk factors possess a significant genetic component, but the evidence
[11]
of the role of genetic factors in risk factor clustering in individuals remains uncertain .
It has recently been shown that several mutations of mtDNA are associated with atherosclerosis. Namely,
heteroplasmic mutations m.652delG, m.1555A>G, m.3336T>C, m.3256C>T, m.5178C>A, m.12315G>A,
m.13513G>A, m.14459G>A, m.14846G>A, and m.15059G>A were found in atherosclerotic plaques of human
aortic intima, and there were significant differences in the heteroplasmy level between unaffected and
atherosclerotic tissues. These mutations occurred in mitochondrial genes MT-RNR1 (rRNA 12S); MT-TL1
and MT-TL2 (tRNA-Leu); MT-ND1, MT-ND2, MT-ND5, and MT-ND6 (subunits 1, 2, 5 and 6, of NADH
dehydrogenase, respectively), and MT-CYB (cytochrome b) [12-15] . Further, most of these mutations were
found to be associated with the severity of carotid atherosclerosis and, with lesser extent, the presence of
coronary heart disease [16-20] .

Since MetS shares common risk factors with atherosclerosis and, moreover, is considered itself as the
independent risk factor for atherosclerosis, this study was performed to test the hypothesis that MetS and
atherosclerosis-related heteroplasmic mtDNA mutations are associated.