Salt Sensitivity of Blood Pressure in Black Individuals with Striatin and Lysine Specific Demethylase-1 Risk Alleles

Abstract

Background: 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.

Methods: 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.

Results: 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 versus the Lower Risk groups (18.9 ± 1.8 mmHg vs 10.8 ± 1.6 mmHg, p-value < 0.0001). Among hypertensive individuals, SSBP was 22.9 ± 2.5 mmHg vs 12.9 ± 2.1 mmHg for the Higher Risk vs Lower Risk groups, respectively (p-value <0.0001). These results were confirmed in a second cohort of 37 Black individuals (p-value=0.029). In 396 White individuals, no differences were observed.

Conclusion: 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.