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Sazonova et al. Threshold heteroplasmy levels of atherogenic mutations

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.

INTRODUCTION arteries (IMT CA); (3) with a normal carotid intima.

Atherosclerosis of human major vessels is often a It should be emphasized that at the present time there
morphological basis of mortality from cardiovascular are no published studies which have investigated the
diseases. In this pathology intima of arteries is threshold heteroplasmy level of mitochondrial genome
damaged, luminal occlusion occurs and blood supply mutations in atherosclerosis. Therefore, this article,
to organs deteriorates [1-5] . Atherosclerosis is difficult dedicated to the identification of this parameter in
to recognize in the early stages. Molecular genetic patients with atherosclerotic lesions in blood vessels’
markers could help the diagnostics of this disease. wall, is quite relevant, well-timed and novel.
Unfortunately, compared to traditional single risk
factors of atherosclerosis, nuclear genome mutations METHODS
have rather low diagnostic and prognostic significance.
The relative risk of one such mutation is 1.06-1.40. Inclusion criteria
The total risk of cardiovascular diseases caused The present research was carried out according to the
due to all known mutations in the nuclear genome is Helsinki Declaration of 1975 as revised in 1983. It was
approximately 5% [6-10] . endorsed by the local ethics committees of the Institute
for Atherosclerosis Skolkovo Innovation Center,
According to the literature, a variety of diseases is Moscow, Russia and Research Institute of General
associated with some mutations in mitochondrial Pathology and Pathophysiology, Moscow. Prior to their
DNA (mtDNA). These mutations often correlate inclusion in the study, all the study participants gave an
with pathologies which often occur together with informed consent in written form.
atherosclerosis [11-15] . The penetrance of mtDNA
mutations depends on the percentage of normal The participants in the study were enrolled consecutively
and mutant copies of genome, i.e. the heteroplasmy from the number of patients at Moscow municipal
level of mitochondrial mutations. That is why, during outpatient clinics No. 202, who were examined for
the analysis of the linkage of mitochondrial genome cardiovascular risk factors (mainly arterial blood
mutations with human diseases, the value of pressure and blood cholesterol). The investigated
heteroplasmy level above which in a person begins sample included 700 study participants. The age of
the occurrence and development of pathologies men was over 40-year-old, and the age of women was
or begins to show a protective effect caused by over 50 [20,21] . The average age of the participants in
mutations is determined. The information about the the sample was 62.3 years (SD = 8.7), the ratio of men
threshold heteroplasmy level of mitochondrial genome and women was 362:338 (51.7%/48.3%). As a result of
mutations associated with certain diseases, can help ascertaining the clinical diagnosis of atherosclerosis,
in assessing the predisposition and the early diagnosis the sample was divided into 2 groups: (1) conventionally
of these pathologies. healthy participants without ultrasonographic signs
of atherosclerosis (339 people, or 48.4% of the
In preliminary studies, a total of 11 of 42 mtDNA sample); (2) patients without clinical manifestations of
mutations associated with different pathologies was atherosclerosis who have ultrasonographic signs of
found to have an association with atherosclerosis [16-19] . preclinical atherosclerosis: the presence of lesions in
In view of these facts, the aim of the present article the carotid artery lumen (more than 10% of the artery
was the detection of threshold heteroplasmy level lumen) (361 people, or 51.6% of the sample).
of mtDNA mutations, above which atherosclerotic
lesions were found in patients. Besides, this parameter The criteria for exclusion were: anatomical organization
was detected for mutations, in which after reaching of the neck and carotid arteries which prevented
the threshold heteroplasmy level started to appear a qualitative ultrasonography, serious life-threatening
protective antiatherogenic effect. diseases and the refusal to sign an informed consent
to the investigation. Individuals with a history of, or a
The estimation of the mutations’ threshold heteroplasmy diagnoses of the following diseases were excluded from
level was carried out in the following samples of the the study: breast cancer or nodal form of mastopathy;
study participants: (1) with atherosclerotic plaques; (2) stroke or coronary heart disease; liver dysfunction;
with an increased intima-medial thickness of carotid chronic kidney disease; type 2 diabetes; obesity (body

Vessel Plus ¦ Volume 1 ¦ December 28, 2017 183