MtDNA mutations linked with left ventricular hypertrophy

Abstract

Aim: In left ventricular hypertrophy (LVH), the heart muscle thickens. One third of individuals with LVH never complain of heart problems. However, such patients have a high risk of sudden death. LVH can be caused by arterial atherosclerotic lesions. The linkage of mtDNA mutations 652insG, m.5178C>A, m.3336T>C, m.14459G>A, 652delG, m.14846G>A, m.1555A>G, m.15059G>A, m.3256C>T, m.12315G>A and m.13513G>A with atherosclerosis was described earlier by our laboratory. The aim of the study was to analyze the linkage of these mtDNA mutations with LVH. Methods: DNA from white blood cells was isolated using a phenol-chloroform method. PCR-fragments of DNA contained the region of the investigated mutations. The heteroplasmy level of mtDNA mutations was analyzed using a pyrosequencing-based method developed by our laboratory. Results: We investigated two groups of individuals. One hundred and ninety-four patients with LVH. Two hundred and ten were conventionally healthy. It was found that mtDNA mutation m.5178C>A was significantly associated with LVH. Single nucleotide replacement m.1555A>G was associated with LVH at the level of significance P ≤ 0.1. At the same time m.12315G>A and m.3336T>C were significantly associated with the absence of this pathology. Single nucleotide replacement m.14459G>A was associated with the absence of LVH at the significance level P ≤ 0.1. Conclusion: MtDNA mutations m.5178C>A and m.1555A>G can be used for molecular genetic assessment of the predisposition of individuals to the occurrence of left ventricular hypertrophy. They can also be used for the family analysis of this pathology. Mutations m.12315G>A, m.3336T>C and m.14459G>A can be used in the development of LVH gene therapy methods.

Some Molecular and Cellular Stress Mechanisms Associated with Neurodegenerative Diseases and Atherosclerosis

“…Most of mutations, linked with atherosclerosis, cardiovascular diseases and aging, belong to genes of subunits of mitochondrial respiratory chain enzymes ( MT-ND1 , MT-ND2 , MT-ND5 , MT-ND6 , MT-CYTB ) [ 18 , 235 , 245 , 246 , 247 , 248 , 249 ]. The occurrence of such mutations can lead to energy deficiency in cells, for the reason of enzyme dysfunction [ 18 , 235 , 245 , 246 , 247 , 248 ]. This, in its turn, can lead to mitochondrial dysfunction and oxidative stress in cells and in the human organism.…”

“…Part of the detected mutations belongs to tRNA genes ( MT-TL1 , MT-TL2 ) and rRNA (MT- RNR1 ). Mutations in these genes can lead to dysfunction of tRNA and rRNA [ 18 , 235 , 245 , 246 , 247 ]. As a result, the amount of normal RNA and proteins in mitochondria decreases.…”

Creation of Cybrid Cultures Containing mtDNA Mutations m.12315G>A and m.1555G>A, Associated with Atherosclerosis

“…Every year, a large number of people die of it [11,12,13,14,15]. According to the literature, one of the causes of atherosclerosis is mitochondrial dysfunction [16,17,18,19,20]. In particular, the association of atherosclerosis with mitophagy was detected [16,17,18].…”

“…According to the literature, one of the causes of atherosclerosis is mitochondrial dysfunction [16,17,18,19,20]. In particular, the association of atherosclerosis with mitophagy was detected [16,17,18]. Signal pathways that link mitochondrial dysfunction with shortening of telomeres, oxidative stress, and atherosclerosis were found [18,19,20,21].…”

“…In particular, the association of atherosclerosis with mitophagy was detected [16,17,18]. Signal pathways that link mitochondrial dysfunction with shortening of telomeres, oxidative stress, and atherosclerosis were found [18,19,20,21]. Moreover, it was found that metabolic disorders can lead to a defect in the mitochondrial membrane, leading to mitochondrial dysfunction.…”