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Sinyov et al. mtDNA mutations in buccal epithelium

Table 1: Significance of rank differences in heteroplasmy levels between human buccal epithelium and whole blood
m.12315G>A m.13513G>A m.1555A>G m.3256C>T m.3336T>C
Mann-Whitney U-test 8,167 7,761 7,625 6,554 595
P value 0.20 0.18 0.36 0.08 0.80

Table 2: Ranking of atherosclerotic plaques in the mitochondrial genome mutations associated with this
lumen of blood vessels of the brachiocephalic bed, disease.
depending on the degree of stenosis
Atherosclerotic plaque size (points) Degree of stenosis (%) To check the distribution of heteroplasmy values in
0 0 different cell types and their association with gender,
1 < 20 age, the degree of angiostenosis, and IMT, a correlation
2 20-40 analysis of heteroplasmy levels in the buccal epithelium
3 > 40
and whole blood was carried out. The parametric
variables of age and IMT were compared with the
heteroplasmy level of mitochondrial genome mutations average heteroplasmy levels of the mitochondrial
on different human diseases can be evaluated using genome mutations m.12315G>A, m.13513G>A,
the percentage expression of mutational burden. To m.1555А>G, m.3256C>T, and m.3336T>C, while the
determine the difference in heteroplasmy levels among non-parametric variables of atherosclerotic plaques and
samples, it is necessary to convert heteroplasmy gender were compared with threshold heteroplasmy
levels into rank values using the threshold value of level distributions. Variability was assessed according
heteroplasmy percentage. It should be noted that, to the available data on the size of an atherosclerotic
despite the fact that the average heteroplasmy level plaque (in points) [Table 2].
for a number of mutations was much lower than
the threshold level (e.g. for mutation m.13513G>A, A correlation analysis was performed between the
the threshold heteroplasmy level was 32.5% while threshold levels of heteroplasmy in the mitochondrial
the average value of this parameter for the buccal genome mutations m.12315G>A, m.13513G>A,
epithelium and whole blood was 15% and 14%, m.1555А>G, m.3256C>T, and m.3336T>C in the buccal
respectively), some individuals had heteroplasmy epithelium and whole blood, and the atherosclerotic
levels above the threshold level. plaque size, IMT, age, and gender of individuals from the
investigated sample [Tables 3 and 4]. The differences
After ranking the heteroplasmy levels, differences were considered significant at 95% probability of
in the mutational burden distribution in buccal faultless prognosis. These analyses found that the
epithelium and whole blood were determined using heteroplasmy level of mutation m.1555А>G in the
the Mann-Whitney U-test [Table 1]. As can be seen buccal epithelium was significantly positively correlated
in Table 1, the threshold heteroplasmy level of the with IMT and negatively correlated with age [Table 3].
mutations m.12315G>A, m.13513G>A, m.1555А>G, In whole blood, the heteroplasmy level of mutation
m.3256C>T, and m.3336T>C, which are associated m.1555А>G was significantly positively correlated with
with atherosclerotic plaques, did not significantly differ IMT, similar to the correlation in the buccal epithelium.
between the buccal epithelium and whole blood.
DISCUSSION
Consequently, DNA samples from both the buccal
epithelium and the whole blood may be of use for the A range of scientific publications have indicated that
molecular genetic diagnosis of atherosclerosis using mitochondrial genome mutations, which are associated

Table 3: Correlation of heteroplasmy level of mtDNA mutations in human buccal epithelium with plaques, IMT,
gender, and age
Variable m.13513G>A m.12315G>A m.1555A>G m.3256C>T m.3336T>C
Plaque Spearman correlation coefficient 0.09 0.03 -0.11 -0.12 -0.02
P value 0.31 0.78 0.22 0.19 0.81
Gender Spearman correlation coefficient 0.02 -0.02 0.15 -0.16 -0.10
P value 0.87 0.79 0.10 0.10 0.33
Age Pearson correlation coefficient -0.07 -0.13 -0.33* -0.21 -0.06
P value 0.40 0.16 0.01 0.20 0.56
IMT Pearson correlation coefficient -0.07 0.14 0.53* 0.04 -0.05
P value 0.40 0.12 0.01 0.67 0.61
*Highly significant. mtDNA: mitochondrial DNA; IMT: intima-medial thickness
148 Vessel Plus ¦ Volume 1 ¦ September 26, 2017