Dysregulated aldosterone secretion in persons of African descent with endothelin-1 gene variants

Sex-specific differences in endoplasmic reticulum aminopeptidase 1 modulation influence blood pressure and renin-angiotensin system responses

“…To determine how our rodent studies relate to humans, we characterized individuals from the highly environmentally controlled HyperPATH cohort (16,22,23) who were carriers of the ERAP1 rs30187 risk allele. Our results show that as observed in male ERAP1 +/mice, men who carry the rs30187 risk allele have increased BP on a liberal-salt diet, and this increase follows an allelic dose response.…”

“…Data were evaluated from a cohort of participants of the multisite HyperPATH consortium developed to characterize the genetic underpinnings of HTN. A detailed description of this population has been published previously (16,23,(44)(45)(46)(47). Data from some of these subjects have been previously reported; however, the analyses and results shown herein have not.…”

“…Genotyping. DNA was obtained from stored leukocytes, using procedures previously described by us, from the Crimson Biospecimen Core (QIAGEN) (23). Genotyping was done at the Partners Health-Care Center for Personalized Genetic Medicine (PCPGM) Genotyping Facility using the Illumina Bead Station GoldenGate platform.…”

“…Blood pressure was recorded by an automatic recording device (Dinamap, Critikon) at 5-minute intervals and averaged for analysis. RPF was determined by PAH clearance as previously reported (16,23,(44)(45)(46)(47).…”

“…Analyte measurements. Hormones and electrolytes in serum and urine were measured in the Brigham and Women's Hospital's Research Assay Core Laboratory as previously reported (22,23). ALDO levels were measured by using a Coat-A-Count RIA kit (Siemens); PRA by RIA assay (DiaSorin); and ANGII and PAH by LC-MS.…”