Abstract
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.
Highlights
Current knowledge about the mechanisms of atherosclerosis development has significantly increased in recent decades, but atherosclerotic-based diseases still occupy a leading position in the structure of mortality in developed countries [1]
It was demonstrated that variants of mitochondrial heteroplasmy m.15059G>A, m.12315G>A, m.5178C>A, and m.3256C>T significantly correlated with the intima-media thickness of common carotid arteries; a negative correlation of m.13513G>A and m.14846G>A with mean cIMT was revealed
In subjects derived from a Kazakhstan population, m.12315G>A was associated with cIMT only in women, but a negative correlation of m.13513G>A with cIMT was confirmed in the total group [16]
Summary
Current knowledge about the mechanisms of atherosclerosis development has significantly increased in recent decades, but atherosclerotic-based diseases still occupy a leading position in the structure of mortality in developed countries [1]. In this regard, the early detection and treatment of patients with a high risk of atherosclerosis development is a primary medical and social problem. The thickness of the intimal-medial layer of the carotid arteries (cIMT) is considered to be a direct non-invasive marker of subclinical atherosclerosis, used in clinical and epidemiological studies to assess the effect of conventional and new cardiovascular risk factors (CVRFs) on the progression of atherosclerotic lesions [2,3]. Conventional CVRFs are poorly associated with cIMT, which suggests the presence of other factors determining the risk atherosclerosis development [4,5]
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