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Sinyov et al. mtDNA mutations in buccal epithelium

Table 4: Correlation of heteroplasmy level of mtDNA mutations in human whole blood 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 -0.01 -0.08 0.04 -0.02 -0.08
P value 0.89 0.37 0.66 0.82 0.42
Gender Spearman correlation coefficient 0.10 -0.11 0.11 0.10 -0.10
P value 0.29 0.21 0.22 0.30 0.32
Age Pearson correlation coefficient 0.04 0.08 -0.07 -0.11 0.03
P value 0.68 0.34 0.43 0.25 0.79
IMT Pearson correlation coefficient 0.35 0.05 0.26* 0.07 -0.01
P value 0.10 0.56 0.01 0.49 0.91
*Highly significant. mtDNA: mitochondrial DNA; IMT: intima-medial thickness
with several human diseases, can be unequally suggest that defects in mitochondrial ribosomes can
distributed in tissues and organs. [15,16] This has been lead to a decrease in the protein chains of respiratory
shown in research with both healthy participants enzymes. This might result in decreased ATP synthesis
and those affected by disease. [17,18] Therefore, we in cells, leading to oxidative stress and the unlimited
studied the heteroplasmy levels of the mutations proliferation of mutant cells. Such a process might
m.12315G>A, m.13513G>A, m.1555А>G, m.3256C>T, culminate in increased IMT in the carotid arteries
and m.3336T>C, which have been associated with and the formation of atherosclerotic plaques (i.e.
atherosclerosis, and the distribution of these mutations atherosclerosis).
in different tissues and organs. To compare different
cells and tissues, we used the parameter of the In conclusion, the buccal epithelium and whole
threshold heteroplasmy level of mutations. This enabled blood are quite common subjects of investigation
us to calculate average differences in heteroplasmy in medicine, in particular in the genetic diagnosis of
levels among samples from various participants. various human diseases. The data obtained during the
This parameter was calculated on the basis of the present study suggest that DNA samples from either
correlation between mtDNA mutations and the degree the buccal epithelium or whole blood can be used to
of atherosclerosis of the arterial vessel wall. The determine the heteroplasmy levels of the mitochondrial
[9]
results indicate the absence of significant differences genome mutations m.12315G>A, m.13513G>A,
in threshold heteroplasmy levels of the mitochondrial m.1555A>G, m.3256C>T, and m.3336T>C, which
genome mutations m.12315G>A, m.13513G>A, have been associated with atherosclerosis. It should
m.1555А>G, m.3256C>T, and m.3336T>C between be emphasized that buccal epithelial samples are far
human buccal epithelium and whole blood. In addition, easier to collect, making this a preferable tissue for
we studied the variability of heteroplasmy levels in the studying the association of mitochondrial genome
same mutations in participants with different IMTs and mutations with atherosclerosis and the search for new
different degrees of luminal occlusion. No correlation biomarkers.
between the heteroplasmy level of mtDNA mutations
and atherosclerotic plaque size was found. This may These findings will be of particular interest to specialists
indicate an insufficient sample size to identify such a in medical genetics and medical practitioners.
relationship. However, a significant direct correlation
of mutation m.1555А>G with IMT was detected for Authors’ contributions
DNA samples from both the buccal epithelium and Manuscript’s conception and writing: V.V. Sinyov, M.A.
whole blood. In line with previous research, [16,19-21] we Sazonova, A.Y. Postnov, A.N. Orekhov
found no correlation between the level of mutational Data base fulfillment: V.V. Sinyov, M.A. Sazonova, A.I.
burden and either gender or age, apart from an inverse Ryzhkova, E.V. Galitsyna, A.A. Melnichenko
correlation of mutation m.1555А>G with age in buccal Manuscript’s revision: A.V. Grechko, I.A. Sobenin
epithelial samples.
Financial support and sponsorship
It is possible that the data on mutation m.1555A>G
indicate that individuals with a high heteroplasmy This study was supported by the Russian Science
level of this mutation may have a higher IMT than their Foundation (grant #14-14-01038).
peers with lower heteroplasmy levels. It is important
to note that mutation m.1555A>G is localized in the Conflicts of interest
gene of subunit 12S of the mitochondrial genome. The The authors declare that the research was conducted
association of this mutation with increased IMT may in the absence of any commercial or financial

Vessel Plus ¦ Volume 1 ¦ September 26, 2017 149