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

Abstract

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.