Page 53 - Read Online

Page 2 of 9 Sazonova et al. Vessel Plus 2019;3:5 I http://dx.doi.org/10.20517/2574-1209.2018.56

Keywords: Left ventricular hypertrophy, heteroplasmy level, mutation, mitochondrial genome, mtDNA

INTRODUCTION
In case of left ventricular hypertrophy (LVH), the heart muscle thickens. Often septum between the left and
[1]
right ventricles mutates in this disease . In LVH muscle fibers in the myocardium are arranged randomly.
The main criterion for LVH is considered to be an increase in myocardial thickness larger than or equal to
[1-3]
1.5 cm in the presence of left ventricular diastolic dysfunction . The third part of individuals with LVH
never complain of heart problems. However, such patients have a high risk of sudden death, which reaches
[2,3]
4% per year . Echocardiography helps to identify such patients. It can be used to identify a left ventricle
and left atrium enlargements. It can also detect heart rhythm disorders. This helps to assess the risk of
sudden death. About 50% of deaths from left ventricular hypertrophy per year happen precisely because of
ventricular arrhythmias. The second cause of death of patients with LVH is congestive heart failure. It is
[4,5]
most common in patients older than 40 years .

The onset and development of left ventricular hypertrophy can be caused by atherosclerotic lesions of the
arteries, in particular, atherosclerotic plaques and thickening of the intima-medial layer of these vessels [6-10] .
Risk factors for LVH include diabetes mellitus, stress, smoking, hyperlipoproteinemia, hypodynamia,
arterial hypertension, hyperfibrinogenemia, homocysteinemia, obesity, hypothyroidism and metabolic
syndrome [11-15] .

In addition, left ventricular hypertrophy may occur due to hereditary and somatic mutations of the human
genome. At present, many scientists are studying, basically, the single-nucleotide polymorphism (SNP) of
the nuclear genome associated with this pathology [16-20] . However, nuclear polymorphisms are associated
only with a small number of LVH cases. Meanwhile mitochondrial genome mutations with left ventricular
hypertrophy were analyzed by a very small number of research groups around the world [21-23] .

It should be noted that in human cells there are plenty of mitochondria. Each mitochondria contains
several copies of the mitochondrial genome. Therefore, during the analysis of DNA samples from the study
participants it is necessary to determine the heteroplasmy level of each investigated mitochondrial genome
mutation (ratio of mtDNA molecules containing the mutation to the total number of mtDNA molecules) [24-28] .
It differs significantly from SNP analysis of the nuclear genome, where it is necessary to identify homozygous
and heterozygous individuals according to this SNP.

The linkage of mtDNA mutations 652insG, m.5178C>A, m.3336T>C, m.14459G>A, 652delG, m.14846G>A,
m.1555A>G, m.15059G>A, m.3256C>T, m.12315G>A and m.13513G>A with atherosclerosis was described
earlier by our laboratory researchers [24,28-31] . Since LVH has common risk factors with atherosclerosis, it was
decided to analyze the relationship of these mutations to mtDNA with left ventricular hypertrophy.

METHODS
In this study two groups of study participants were examined. One hundred and ninety-four patients had
left ventricular hypertrophy. Two hundred and ten study participants were conventionally healthy. For
identifying patients with LVH among the study participants, the method of echocardiography was used.
The main criterion of LVH was considered to be an increase in myocardial thickness of more than or
equal to 1.5 cm in the presence of left ventricular diastolic dysfunction. Individuals with diabetes mellitus,
hypercholesterolemia and patients, who used drugs, were excluded from the study. In order to compare the
samples of patients with LVH and conventionally healthy study participants more correctly, the composition
of the samples was changed so that they did not contain significant differences in age, sex, diastolic and
systolic blood pressure.