Type: Conference abstract and poster presentation
Abstract:
Hypertension directly affects about one in five adults in United States and approximately 1,300 Americans die from hypertension-related causes every day. Hypertension is known to be highly heritable through genetics; however, the effect of genetic variants in blood pressure regulation is not well established. In a 200,000-individual genome study, we identified five single nucleotide polymorphisms (SNPs) on the calcineurin homologous protein (CHP) genes that were significantly correlated with increased blood pressure. Using computational analysis, we mapped the SNPs location within putative transcription factor binding sites in non-coding regions of CHP genes. CHP is a binding partner of Na+/H+ exchanger-3 (NHE3), a key player in renal salt regulation and blood pressure control. Furthermore, the level of CHP protein expression is known to regulate NHE3 activity. We hypothesized that these SNPs affect NHE3 activity through CHP gene regulation, with a downstream effect on blood pressure. We cloned the human CHP promoters and measured activity of each SNP on its respective CHP promoter expressed in human kidney cells using the luciferase reporter system. Major to minor allele replacements of three of four SNPs revealed significant effects on CHP promoter activity. Expression of the other one SNP did not show a significant effect on promoter activity. Ongoing research involves identifying changes in the binding of transcription factors to SNP regions of CHP genes dependent on the switch from major to minor alleles. Functional analysis of CHP genetic variants might aid the discovery of novel susceptibility loci responsible for genetic predisposition to the development of hypertension.
Conference:
Experimental Biology 2021
Publication Date:
May 14, 2021
DOI:
Tom Fusillo, DO, MS, MHA 