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Sazonova et al. Threshold heteroplasmy levels of atherogenic mutations

Table 2: The threshold value of heteroplasmy level of ROC curve
mtDNA mutations associated with atherosclerosis 1.0
Threshold
Threshold value value of
of heteroplasmy 0.8
Gene Mutation level in heteroplasmy
level in
atherosclerotic thickened
plaques (%)
IML CA (%) 0.6
MT-TL1 m.3256C>T 15.5 16.5
MT-RNR1 m.652delG 20.5 21.5 Sensitivity
MT-CYTB m.14846G>A* 17.5 17.5 0.4
MT-TL2 m.12315G>A 7.5 10.5
MT-ND1 m.3336T>C 6.5 7.5
MT-RNR1 m.652insG 20.0 20.0 0.2
MT-CYTB m.15059G>A 24.5 26.5
MT-RNR1 m.1555A>G* 17.5 19.5
MT-ND5 m.13513G>A* 32.5 33.5
MT-ND2 m.5178C>A 6.5 6.5 0.0
MT-ND6 m.14459G>A 4.5 4.5 0.0 0.2 0.4 0.6 0.8 1.0
1 - Specificity
*: antiatherosclerotic mutations; IML CA: intima-medial layer of Figure 1: ROC-curve for the analysis of the link of the heteroplasmy
carotid arteries level in mitochondrial genome mutation m.12315G>A with the
occurrence of atherosclerotic plaques in carotid arteries: area
Table 3: Detection of the optimal threshold heteroplasmy under the curve 0.577 (standard error 0.015); P ≤ 0.042. ROC:
level value for m.12315G>A on the basis of ROC-analysis receiver operating characteristic
Coordinates of the curve DISCUSSION
Threshold Sensitivity 1 - Specificity
heteroplasmy level
4.50 0.825 0.795 Atherosclerosis of human major vessels is often a
5.50 0.789 0.667 cause of mortality from cardiovascular diseases.
6.50 0.719 0.643 In this pathology, the intima of arteries is damaged,
7.50 0.684 0.608 luminal occlusion occurs and blood supply to
8.50 0.632 0.544 organs deteriorates [1-5] . Atherosclerosis is difficult
9.50 0.614 0.485 to recognize in the early stages. Molecular genetic
10.50* 0.596 0.468
11.50 0.579 0.468 markers could help the diagnostics of this disease.
12.50 0.561 0.433 Unfortunately, compared to traditional single risk
13.50 0.544 0.415 factors of atherosclerosis, nuclear genome mutations
14.50 0.544 0.398 have rather low diagnostic and prognostic significance.
16.00 0.526 0.363
17.50 0.474 0.339 According to the literature, a variety of diseases is
18.50 0.421 0.310 associated with some mutations in mtDNA. These
19.50 0.404 0.287 mutations often correlate with pathologies which
20.50 0.386 0.269 [11-15]
21.50 0.386 0.246 often occur together with atherosclerosis . The
22.50 0.351 0.24 penetrance of mtDNA mutations depends on the
23.50 0.333 0.228 percentage of normal and mutant copies of genome,
24.50 0.333 0.216 i.e. the heteroplasmy level of mitochondrial mutations.
25.50 0.316 0.193 That is why, during the analysis of the linkage of
26.50 0.298 0.187 mitochondrial genome mutations with human diseases,
27.50 0.298 0.181
the value of heteroplasmy level above which a person
ROC: receiver operating characteristic begins the occurrence and development of pathologies
or begins to show a protective effect of mutations
It is necessary to mention that during the analysis needs to be determined. The information about the
of all the 11 investigated mutations in patients, it threshold heteroplasmy level of mitochondrial genome
was possible to explain more than 84% of cases of mutations, associated with certain diseases, can help
atherosclerotic plaques occurrence and thickening of in assessing the predisposition and the early diagnosis
intima-medial layer of carotid arteries. of these pathologies.

Vessel Plus ¦ Volume 1 ¦ December 28, 2017 187