Cargando…

Impact of Mitochondrial DNA Mutations on Carotid Intima-Media Thickness in the Novosibirsk Region

The search for markers of predisposition to atherosclerosis development is very important for early identification of individuals with a high risk of cardiovascular disease. The aim of the present study was to investigate the association of mitochondrial DNA mutations with carotid intima-media thick...

Descripción completa

Detalles Bibliográficos
Autores principales: Kirichenko, Tatiana V., Ryzhkova, Anastasia I., Sinyov, Vasily V., Sazonova, Marina D., Orekhova, Varvara A., Karagodin, Vasily P., Gerasimova, Elena V., Voevoda, Mikhail I., Orekhov, Alexander N., Ragino, Yulia I., Sobenin, Igor A., Sazonova, Margarita A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7554768/
https://www.ncbi.nlm.nih.gov/pubmed/32842589
http://dx.doi.org/10.3390/life10090160
_version_ 1783593850821935104
author Kirichenko, Tatiana V.
Ryzhkova, Anastasia I.
Sinyov, Vasily V.
Sazonova, Marina D.
Orekhova, Varvara A.
Karagodin, Vasily P.
Gerasimova, Elena V.
Voevoda, Mikhail I.
Orekhov, Alexander N.
Ragino, Yulia I.
Sobenin, Igor A.
Sazonova, Margarita A.
author_facet Kirichenko, Tatiana V.
Ryzhkova, Anastasia I.
Sinyov, Vasily V.
Sazonova, Marina D.
Orekhova, Varvara A.
Karagodin, Vasily P.
Gerasimova, Elena V.
Voevoda, Mikhail I.
Orekhov, Alexander N.
Ragino, Yulia I.
Sobenin, Igor A.
Sazonova, Margarita A.
author_sort Kirichenko, Tatiana V.
collection PubMed
description The search for markers of predisposition to atherosclerosis development is very important for early identification of individuals with a high risk of cardiovascular disease. The aim of the present study was to investigate the association of mitochondrial DNA mutations with carotid intima-media thickness and to determine the impact of mitochondrial heteroplasmy measurements in the prognosis of atherosclerosis development. This cross-sectional, population-based study was conducted in 468 subjects from the Novosibirsk region. It was shown that the mean (carotid intima-media thickness) cIMT correlated with the following mtDNA mutations: m.15059G>A (r = 0.159, p = 0.001), m.12315G>A (r = 0.119; p = 0.011), m.5178C>A (r = 0.114, p = 0.014), and m.3256C>T (r = 0.130, p = 0.011); a negative correlation with mtDNA mutations m.14846G>A (r = −0.111, p = 0.042) and m.13513G>A (r = −0.133, p = 0.004) was observed. In the linear regression analysis, the addition of the set of mtDNA mutations to the conventional cardiovascular risk factors increased the ability to predict the cIMT variability from 17 to 27%. Multi-step linear regression analysis revealed the most important predictors of mean cIMT variability: age, systolic blood pressure, blood levels of total cholesterol, LDL and triglycerides, as well as the mtDNA mutations m.13513G>A, m.15059G>A, m.12315G>A, and m.3256C>T. Thus, a high predictive value of mtDNA mutations for cIMT variability was demonstrated. The association of mutation m.13513G>A and m.14846G>A with a low value of cIMT, demonstrated in several studies, represents a potential for the development of anti-atherosclerotic gene therapy.
format Online
Article
Text
id pubmed-7554768
institution National Center for Biotechnology Information
language English
publishDate 2020
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-75547682020-10-14 Impact of Mitochondrial DNA Mutations on Carotid Intima-Media Thickness in the Novosibirsk Region Kirichenko, Tatiana V. Ryzhkova, Anastasia I. Sinyov, Vasily V. Sazonova, Marina D. Orekhova, Varvara A. Karagodin, Vasily P. Gerasimova, Elena V. Voevoda, Mikhail I. Orekhov, Alexander N. Ragino, Yulia I. Sobenin, Igor A. Sazonova, Margarita A. Life (Basel) Article The search for markers of predisposition to atherosclerosis development is very important for early identification of individuals with a high risk of cardiovascular disease. The aim of the present study was to investigate the association of mitochondrial DNA mutations with carotid intima-media thickness and to determine the impact of mitochondrial heteroplasmy measurements in the prognosis of atherosclerosis development. This cross-sectional, population-based study was conducted in 468 subjects from the Novosibirsk region. It was shown that the mean (carotid intima-media thickness) cIMT correlated with the following mtDNA mutations: m.15059G>A (r = 0.159, p = 0.001), m.12315G>A (r = 0.119; p = 0.011), m.5178C>A (r = 0.114, p = 0.014), and m.3256C>T (r = 0.130, p = 0.011); a negative correlation with mtDNA mutations m.14846G>A (r = −0.111, p = 0.042) and m.13513G>A (r = −0.133, p = 0.004) was observed. In the linear regression analysis, the addition of the set of mtDNA mutations to the conventional cardiovascular risk factors increased the ability to predict the cIMT variability from 17 to 27%. Multi-step linear regression analysis revealed the most important predictors of mean cIMT variability: age, systolic blood pressure, blood levels of total cholesterol, LDL and triglycerides, as well as the mtDNA mutations m.13513G>A, m.15059G>A, m.12315G>A, and m.3256C>T. Thus, a high predictive value of mtDNA mutations for cIMT variability was demonstrated. The association of mutation m.13513G>A and m.14846G>A with a low value of cIMT, demonstrated in several studies, represents a potential for the development of anti-atherosclerotic gene therapy. MDPI 2020-08-22 /pmc/articles/PMC7554768/ /pubmed/32842589 http://dx.doi.org/10.3390/life10090160 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Kirichenko, Tatiana V.
Ryzhkova, Anastasia I.
Sinyov, Vasily V.
Sazonova, Marina D.
Orekhova, Varvara A.
Karagodin, Vasily P.
Gerasimova, Elena V.
Voevoda, Mikhail I.
Orekhov, Alexander N.
Ragino, Yulia I.
Sobenin, Igor A.
Sazonova, Margarita A.
Impact of Mitochondrial DNA Mutations on Carotid Intima-Media Thickness in the Novosibirsk Region
title Impact of Mitochondrial DNA Mutations on Carotid Intima-Media Thickness in the Novosibirsk Region
title_full Impact of Mitochondrial DNA Mutations on Carotid Intima-Media Thickness in the Novosibirsk Region
title_fullStr Impact of Mitochondrial DNA Mutations on Carotid Intima-Media Thickness in the Novosibirsk Region
title_full_unstemmed Impact of Mitochondrial DNA Mutations on Carotid Intima-Media Thickness in the Novosibirsk Region
title_short Impact of Mitochondrial DNA Mutations on Carotid Intima-Media Thickness in the Novosibirsk Region
title_sort impact of mitochondrial dna mutations on carotid intima-media thickness in the novosibirsk region
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7554768/
https://www.ncbi.nlm.nih.gov/pubmed/32842589
http://dx.doi.org/10.3390/life10090160
work_keys_str_mv AT kirichenkotatianav impactofmitochondrialdnamutationsoncarotidintimamediathicknessinthenovosibirskregion
AT ryzhkovaanastasiai impactofmitochondrialdnamutationsoncarotidintimamediathicknessinthenovosibirskregion
AT sinyovvasilyv impactofmitochondrialdnamutationsoncarotidintimamediathicknessinthenovosibirskregion
AT sazonovamarinad impactofmitochondrialdnamutationsoncarotidintimamediathicknessinthenovosibirskregion
AT orekhovavarvaraa impactofmitochondrialdnamutationsoncarotidintimamediathicknessinthenovosibirskregion
AT karagodinvasilyp impactofmitochondrialdnamutationsoncarotidintimamediathicknessinthenovosibirskregion
AT gerasimovaelenav impactofmitochondrialdnamutationsoncarotidintimamediathicknessinthenovosibirskregion
AT voevodamikhaili impactofmitochondrialdnamutationsoncarotidintimamediathicknessinthenovosibirskregion
AT orekhovalexandern impactofmitochondrialdnamutationsoncarotidintimamediathicknessinthenovosibirskregion
AT raginoyuliai impactofmitochondrialdnamutationsoncarotidintimamediathicknessinthenovosibirskregion
AT sobeninigora impactofmitochondrialdnamutationsoncarotidintimamediathicknessinthenovosibirskregion
AT sazonovamargaritaa impactofmitochondrialdnamutationsoncarotidintimamediathicknessinthenovosibirskregion