Insilico Test of Functional Role of rs8068318 Polymorphism of Arterial Hypertension-Associated TBX2 Candidate Gene

Abstract

Maria Yu. Abramova, Tatyana A. Usacheva, Inna N. Sorokina, Irina N. Verzilina, Irina S. Polyakova, Vladimir F. Kulikovsky

Arterial hypertension is the most common disease, and cardiovascular pathology has for a long time topped the list of causes of global mortality. Despite the large number of scientific works devoted to this problem, the etiology of essential arterial hypertension is unknown. However, in recent years, genetic factors have become highly important, namely, the contribution of individual single nucleotide polymorphisms of various genes encoding single biological pathways that are involved in the development of hypertension. In the course of this study, the functional role of rs8068318 polymorphism of the TBX2 candidate gene associated with the development of arterial hypertension was studied. The selection of the polymorphic locus was based on the data of the catalog of genome-wide association study (GWAS) of the National Human Genome Research Institute. The functional role was evaluated using online software: HaploReg (v4.1), GTExportal, and PolyPhen-2. The already conducted 68 genome-wide studies detected 382 single nucleotide hypertension-associated polymorphisms. The polymorphic locus - rs8068318 - of the TBX2 candidate gene is associated with the development of hypertension in 4 full-genomic studies, two of which examined its involvement in the development of hypertension in the European population. It was established that this SNP is in the area of hypersensitivity to DNase, the region of regulatory DNA motifs to 4 transcription factors; in the field of histones marking promoters and enhancers in 8 tissues; significantly associated with the expression of the TBX2-AS1 gene and the TBX2 gene in various organs and tissues. The polymorphic locus rs8068318 was found to be in disequilibrium in linkage (r2≥0.8) with 15 SNPs, which have significant epigenetic effects. Thus, the polymorphic locus rs8068318 of the TBX2 candidate gene, which is GWAS-significant for AH, and the 15SNPs linked to it have a significant functional role in the body.