TY - JOUR

T1 - Identification of Single-Nucleotide Polymorphisms in Mitochondria-Associated Genes Capable of Affecting the Development of Hypertrophic Cardiomyopathy in Senescence-Accelerated OXYS Rats

AU - Devyatkin, V. A.

AU - Muraleva, N. A.

AU - Kolosova, N. G.

PY - 2020/4/1

Y1 - 2020/4/1

N2 - Hypertrophic cardiomyopathy (HC) is a heterogeneous myocardial disease with a wide range of clinical manifestations, and the risk of its development increases with age against the background of myocardial changes that are characteristic of aging. The contribution of the genetic component to the development of HC is obvious; however, the etiology and pathogenesis of this disease remain unclear in 50% of cases. The goal of the study was to search for single-nucleotide polymorphisms in mitochondria-associated genes, which can contribute to the development of myocardial hypertrophy in senescence-accelerated OXYS rats, based on the results of RNA-Seq. Polymorphisms with a potential negative effect on the function of the protein product in the mitochondria-associated genes Fbxl4 and Slc25a32, mutations in which were not previously associated with HC, were revealed. Changes in the expression of these genes in the myocardium of OXYS rats at different stages of the development of pathological changes indicate that the identified polymorphisms can contribute to the development of HC. Thus, polymorphisms in the genes Fbxl4 and Slc25a32, as well as the genes themselves, can be considered promising molecular targets in the study of the contribution of mitochondrial dysfunction to the development of myocardial hypertrophy.

AB - Hypertrophic cardiomyopathy (HC) is a heterogeneous myocardial disease with a wide range of clinical manifestations, and the risk of its development increases with age against the background of myocardial changes that are characteristic of aging. The contribution of the genetic component to the development of HC is obvious; however, the etiology and pathogenesis of this disease remain unclear in 50% of cases. The goal of the study was to search for single-nucleotide polymorphisms in mitochondria-associated genes, which can contribute to the development of myocardial hypertrophy in senescence-accelerated OXYS rats, based on the results of RNA-Seq. Polymorphisms with a potential negative effect on the function of the protein product in the mitochondria-associated genes Fbxl4 and Slc25a32, mutations in which were not previously associated with HC, were revealed. Changes in the expression of these genes in the myocardium of OXYS rats at different stages of the development of pathological changes indicate that the identified polymorphisms can contribute to the development of HC. Thus, polymorphisms in the genes Fbxl4 and Slc25a32, as well as the genes themselves, can be considered promising molecular targets in the study of the contribution of mitochondrial dysfunction to the development of myocardial hypertrophy.

KW - Fbxl4

KW - Keywords: aging

KW - myocardial hypertrophy

KW - OXYS rats

KW - single-nucleotide polymorphisms

KW - Slc25a32

UR - http://www.scopus.com/inward/record.url?scp=85088159462&partnerID=8YFLogxK

U2 - 10.1134/S2079057020020058

DO - 10.1134/S2079057020020058

M3 - Article

AN - SCOPUS:85088159462

VL - 10

SP - 121

EP - 127

JO - Advances in Gerontology

JF - Advances in Gerontology

SN - 2079-0589

IS - 2

ER -