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. 2020 May 17;21(10):3542.
doi: 10.3390/ijms21103542.

Single-Nucleotide Polymorphisms (SNPs) Both Associated with Hypertension and Contributing to Accelerated-Senescence Traits in OXYS Rats

Vasiliy A Devyatkin  1   2 , Olga E Redina  1 , Natalia A Muraleva  1 , Nataliya G Kolosova  1
Affiliations

Single-Nucleotide Polymorphisms (SNPs) Both Associated with Hypertension and Contributing to Accelerated-Senescence Traits in OXYS Rats

Vasiliy A Devyatkin et al. Int J Mol Sci. .

Abstract

Aging is a major risk factor of numerous human diseases. Adverse genetic variants may contribute to multiple manifestations of aging and increase the number of comorbid conditions. There is evidence of links between hypertension and age-related diseases, although the genetic relationships are insufficiently studied. Here, we investigated the contribution of hypertension to the development of accelerated-senescence syndrome in OXYS rats. We compared transcriptome sequences of the prefrontal cortex, hippocampus, and retina of OXYS rats with the genotypes of 45 rat strains and substrains (which include models with hypertension) to find single-nucleotide polymorphisms (SNPs) both associated with hypertension and possibly contributing to the development of age-related diseases. A total of 725 polymorphisms were common between OXYS rats and one or more hypertensive rat strains/substrains being analyzed. Multidimensional scaling detected significant similarities between OXYS and ISIAH rat genotypes and significant differences between these strains and the other hypertensive rat strains/substrains. Nonetheless, similar sets of SNPs produce a different phenotype in OXYS and ISIAH rats depending on hypertension severity. We identified 13 SNPs causing nonsynonymous amino-acid substitutions having a deleterious effect on the structure or function of the corresponding proteins and four SNPs leading to functionally significant structural rearrangements of transcripts in OXYS rats. Among them, SNPs in genes Ephx1, Pla2r1, and Ccdc28b were identified as candidates responsible for the concomitant manifestation of hypertension and signs of accelerated aging in OXYS rats.

Keywords: SNP; age-related disease; aging; hypertension; senescence-accelerated OXYS rat.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
Analysis of genetic similarities of rat strains and substrains in terms of single-nucleotide polymorphisms (SNPs). The dendrogram is based on the identity of alleles by state. SNPs were identified in the transcriptomes of three tissues of OXYS/Icgn rats and in the corresponding loci of the WAG/GSto-Icgn, ISIAH/Icgn, and Wistar/Icgn rat transcriptomes or genomes available in the databases for the other 42 rat strains and substrains.
Figure 2
Figure 2
Multidimensional-scaling analysis of distances (allele identity by state) between the genotype of OXYS/Icgn rats and genotypes of 12 other hypertensive rat strains and substrains.
Figure 3
Figure 3
Numbers of common SNPs between OXYS rats and hypertensive rat strains. The colors correspond to the SNPs that were identified in one of the strains of hypertensive rats being analyzed.
See this image and copyright information in PMC

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