Bioinformatic analysis of the regulatory potential of tagging SNPs provides evidence of the involvement of genes encoding the heat-resistant obscure (Hero) proteins in the pathogenesis of cardiovascular diseases.

Abstract

Although multiple aspects of molecular pathology underlying cardiovascular diseases (CVDs) have been revealed, the complete picture has yet to be elucidated. In this respect, annotation of the novel links between genes and atherosclerosis is of great importance for cardiovascular medicine. Aligning with our previous research, we aimed to analyze the cardiovascular predisposition contribution of the genes encoding Hero-proteins, polypeptides with chaperone activity. Following bioinformatic sources were utilized to annotate data regarding the cardiovascular contribution of Hero-proteins and their genes: SNPinfo Web Server, The Cardiovascular Disease Knowledge Portal, GTEx Portal, HaploReg, rSNPBase, RegulomeDB, atSNP, Gene Ontology, QTLbase, and the Blood eQTL browser. Almost all analyzed genes were characterized by a very high regulatory potential of tag SNPs (except BEX3). Multiple substantial impacts of the analyzed SNPs on histone modifications, eQTL effects on CVD-related genes, and binding to transcription factors involved in biological processes pathogenetically significant for CVDs have been discovered. Here we provide in silico evidence of the involvement of genes C9orf16 (BBLN), C11orf58, SERBP1, SERF2, and C19orf53 in CVDs and their risk factors (high blood pressure, dyslipidemia, obesity, arrhythmias, etc.), thus revealing Hero-proteins as putative actors in the pathobiology of the heart and vessels.