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Page 8 of 10 Sobenin et al. Vessel Plus 2019;3:14 I http://dx.doi.org/10.20517/2574-1209.2018.63

measure the plaque size and/or the intima-media thickness in a quantitative manner. In our study, the
principal point was the use of cIMT as the continuous variable, which allows further correlation and
regression analyses. Second, statistical analysis has shown that the sample size was insufficient to exclude
type 2 error for mutations m.652delG, m.1555A>G, m.12315G>A, and m.13513G>A. It means that the null-
hypothesis on the presence of the differences for these variables in the case when we failed to observe them
in our study due to insufficient sample size, cannot be rejected.

In conclusion, the phenotype of MetS in this study was not explained directly by atherosclerosis-related
mtDNA variants, or the known proatherogenic mtDNA mutations. By far, it may be hypothesized that
mtDNA-related mechanisms in atherosclerosis and MetS are different, in spite of the similarity of several
phenotypic characteristics. However, there is a convincing evidence that mtDNA damage may play a
mechanistic role in arising and development of cardiovascular and metabolic disorders. Complexity of the
MetS phenotype should be taken into account, as well as the uncertainty about the common pathogenic
mechanisms explaining the clustering of metabolic abnormalities, and modulating effects of lifestyle
[46]
factors . The conventional role of modified low density lipoprotein in the development of atherosclerosis
should be also assumed [47,48] . It may be speculated that the sets of mtDNA mechanistic biomarkers may be
different in MetS and atherosclerosis. As an example, in the East Finland Founder Population Hypertension
Genetics Study (EFFGE) the whole mtDNA was sequenced in 1,204 adult subjects, and the variants with
the strongest association with obesity were retested in 1,656 subjects from the Young Finns Study. At least 7
novel mtDNA variants were found to be associated with body mass index, and 6 - with obesity (body mass
2
index above 30 kg/m ) (J.T. Salonen, personal communication). Interestingly, none of these mtDNA variants
were ever shown to be associated with atherosclerosis or its clinical manifestations (or, more correct, tested
for such association). So, the search for genetic determinants of the MetS remains the challenge.

DECLARATIONS
Authors’ contributions
Concept of the study, general coordination and supervision of the research project, data analysis, statistical
analysis, and manuscript writing: Sobenin IA
Concept elaboration and discussion, and manuscript editing: Salonen JT
MtDNA genotyping: Khasanova ZB, Sinyov VV, Melnichenko AA
Patients’ recruitment, clinical examination and clinical data acquisition: Kirichenko TV, Prokudina AI,
Orekhova VA, Grechko AV

Availability of data and materials
Not applicable.

Financial support and sponsorship
The study was supported by the Russian Science Foundation (Grant #14-14-01038).

Conflicts of interest
All authors declared that there are no conflicts of interest.

Ethical approval and consent to participate
This study was kept in accordance with the Helsinki Declaration of 1975 as revised in 1983, 2008 and 2013.
It was approved by the local ethics committee of the Institute for Atherosclerosis Research, Skolkovo
Innovation Center, Moscow, Russia. All participants gave their written informed consent prior to their
inclusion in the study.

Consent for publication
Not applicable.