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Sazonova et al. Threshold heteroplasmy levels of atherogenic mutations

of the investigated nucleotide corresponding to the individuals with atherosclerotic plaques or an increased
presence of 100% normal copies of the mitochondrial IMT CA was detected. It should be noted that the
genome in the sample; “M” is the height of the peak percentage of mitochondrial genome copies with
of the investigated nucleotide corresponding to the higher than the threshold level was associated with the
presence of 100% mutant copies of the mitochondrial occurrence and development of atherosclerotic lesions
genome in the sample. in patients. At the same time, achieving and exceeding
the threshold heteroplasmy level of antiatherogenic
It should be emphasized that, alongside the genetic mutations is thought to have the effect of lowering
screening, a number of biochemical indicators was incidence of this disease.
investigated in blood of the study participants: total
cholesterol, triglycerides blood sugar level, low and The evaluation results of the threshold heteroplasmy
high density lipoproteins [20,21] . level of mutations in atherosclerotic plaques and an
increased IMT CA of the carotid arteries of the study
RESULTS participants are shown in Table 2.

At the first stage of the study, demographic The selection of the optimal threshold heteroplasmy
characteristics of 700 study participants were obtained level for each investigated mutation was detected using
[Table 1]. The data in this table are presented by ROC-curve analysis. It was based on simultaneous
means of an average value with the standard deviation maximizing of the sensitivity values (Y-axis) and
(in parentheses). minimizing the value (1-specificity) (X-axis). The
example of such a ROC-curve analysis of a mutation
In the group of conventionally healthy participants, m.12315G>A connection with the occurrence of
women predominated, while in the group of patients atherosclerotic plaques in carotid arteries is shown
with pre-clinical atherosclerosis, men predominated [Figure 1 and Table 3].
[Table 1]. Patients with pre-clinical atherosclerosis
were characterized by a significantly older age, and Therefore, the threshold heteroplasmy level for
also by higher levels of total cholesterol and low- mitochondrial genome mutation m.12315G>A
density lipoproteins cholesterol in men (P ≤ 0.01). was found to be a rather strong predictor of the
This group showed a tendency to an increase in the atherosclerotic plaques occurrence in carotid arteries.
frequency of smoking (P ≤ 0.1). In terms of body mass The area of a ROC-curve for this mutation was found to
index, blood pressure and triglyceride levels, there be 0.577. The optimal threshold value of heteroplasmy
were no significant differences between the studied level for m.12315G>A was 10.5% (sensitivity was 0.6;
groups. specificity was 0.53).

At the second stage of the study the threshold As can be seen from the Table 2, the levels of
heteroplasmy level of 11 investigated mutations heteroplasmy of investigated mitochondrial mutations
(m.5178C>A, m.15059G>A, m.652delG, m.13513G>A, in a sample of patients with atherosclerotic plaques
m.14846G>A, m.652insG, m.12315G>A, m.3336T>C, and in a sample of patients with an increased IMT CA
m.1555A>G, m.14459G>A and m.3256C>T) in are approximately the same.

Table 1: Demographic characteristics of the study participants
Conventionally healthy Patients with preclinical
Value Significance
study participants atherosclerosis
Systolic blood pressure (mmHg) 129 (15.7) 141 (14.1) 0.26
Body-weight index (kg/sq.m) 25.6 (7.3) 29.3 (6.4) 0.45
Male:female (number of persons) 159:180 203:158 0.002**
Smoking (%) 20 (10.6) 42 (9.5) 0.10*
Cholesterol LDL (mmol/L) 4.03 (1.07) 4.38 (1.09) 0.001**
Diastolic blood pressure (mmHg) 78 (16.7) 89 (17.3) 0.38
Age (years) 53 (8.5) 64 (8.9) 0.003**
Total cholesterol (mmol/L) 6.39 (1.21) 6.76 (1.09) 0.001**
Triglycerides (mmol/L) 1.48 (0.61) 1.51 (0.64) 0.290
Cholesterol HDL (mmol/L) 1.70 (0.48) 1.53 (0.52) 0.002**

*: the differences between conventionally healthy study participants and patients with atherosclerosis are at the significance level P
≤ 0.1; **: significant differences between conventionally healthy study participants and patients with atherosclerosis; LDL: low-density
lipoproteins; HDL: high-density lipoproteins
186 Vessel Plus ¦ Volume 1 ¦ December 28, 2017