Abstract 12: The Etiology Of Inverse Salt Sensitivity Of Blood Pressure: Mirna-485-5p Binds To The Dopamine Type 2 Receptor (d 2 R) Snp Rs6276 And Decreases D 2 R Expression

Abstract

Inverse salt sensitivity is the paradoxical increase in blood pressure of individuals to a low sodium diet. rs6276, a single nucleotide polymorphism found in the 3’ untranslated region of the D2R gene (DRD2), which is associated with decreased expression and is also associated with the inverse salt sensitive phenotype (ISS). Urine derived renal proximal tubule cells grown from ISS participants with homozygous rs6276 SNPs vs salt resistant (SR) wild type for rs6276 SNPs have decreased expression of D2R as measured by receptor binding studies using BodipyFL-Spiperone (100 nM for 2 hrs, -36.9% ± 2.6% reduction in ISS-10 vs SR-6, n=5, p<0.01). miRNA-485-5p potentially binds to the rs6276 SNP in the 3’ UTR site and therefore could be a member of a newly identified classification of SNPs called miRSNPs. We transfected a miRNA-485-5p miRNA mimic and a miRNA blocker (20 nM for 72 hrs) to determine the effect on D2R expression on both wild type and homozygous variant SNP participant cell lines. Transfection of mir-485-5p only alters the expression of D2R in the ISS cell lines with SNPs (52619 ± 2001 RFU ISS control miRNA vs 69496 ± 2108 RFU ISS-10 miRNA blocker and vs 30434 ± 1824 RFU ISS-10 miRNA mimic, n=9, p<0.01, one-way ANOVA). The miRNA-485-5p blocker was able to return the D2R expression levels back to levels found in SR cells. Further studies are necessary to determine if the miRNA-485-5p mimic enhances and miRNA-485-5p blocker reverses any of the ISS cell phenotypes identified.