Salt Sensitivity of Blood Pressure in Black Individuals With Striatin and Lysine-specific Demethylase-1 Risk Alleles.

Abstract

Risk alleles in lysine-specific demethylase 1 (LSD1) and striatin (STRN) are independently associated with greater salt-sensitive blood pressure (SSBP) and increased aldosterone and/or mineralocorticoid receptor (MR) activity. We tested the hypothesis that Black, but not White, risk allele carriers in both genes would have a more severe degree of SSBP than those carrying a single risk allele from either gene alone. Individuals from the HyperPATH cohort were assessed for blood pressure and hormone levels after controlled low- and liberal-sodium diets. Black and White individuals with genotype data for LSD1 (rs587168) and STRN diplotype (rs888083 and rs6744560) were included. A total of 127 Black individuals were categorized: (1) higher risk: individuals who carried 1 or 2 risk alleles from both LSD1 and STRN and (2) lower risk: individuals who did not meet these criteria. In multivariable analysis, SSBP was higher among the higher risk vs the lower risk groups (18.9 ± 1.8 mm Hg vs 10.8 ± 1.6 mm Hg, P < .0001). Among hypertensive individuals, SSBP was 22.9 ± 2.5 mm Hg vs 12.9 ± 2.1 mm Hg for the higher risk vs lower risk groups, respectively (P < .0001). These results were confirmed in a second cohort of 37 Black individuals (P = .029). In 396 White individuals, no differences were observed. Black, but not White, individuals with risk alleles from both LSD1 and STRN (44% of subjects) exhibited a higher degree of SSBP. In light of the MR-related drivers of SSBP in this population, MR blockade may be particularly effective.