8758 The Amplified Salt Sensitivity of Blood Pressure of Striatin and LSD1 Risk Alleles in Black Individuals

Abstract Disclosure: H. Ngu: None. R. Uddin: None. A.V. Haas: None. M. heydarpour: None. G.H. Williams: None. J.S. Williams: None. The Amplified Salt Sensitivity of Blood Pressure of Striatin and LSD1 Risk Alleles in Black Individuals Background: Salt sensitivity of blood pressure (SSBP) is an important predictor of cardiovascular disease and renal morbidity. Genetic factors are increasingly becoming recognized as risk factors for the development of SSBP. Specifically, risk alleles in lysine specific demethylase 1 (LSD1) and striatin are independently associated with greater SSBP. LSD1 protein is an epigenetic regulator of gene transcription and is associated with increased mineralocorticoid receptor activity while striatin protein is a scaffolding/signaling protein and is associated with increased aldosterone levels. Objective: Given that LSD1 and striatin are both involved in the volume homeostatic pathway (striatin by enhancing aldosterone production and LSD1 by activating the mineralocorticoid receptor), we tested the hypothesis that Black individuals who carry risk alleles in both LSD1 and striatin would have a more severe form of SSBP than those carrying a single risk allele from either gene alone. Methods: Data was obtained from the international HyperPATH cohort. Hypertensive individuals studied in HyperPATH stopped antihypertensive medication for at least 2 weeks prior to entering the study. Individuals completed assessments for blood pressure and hormone levels after 7 days of a restricted sodium diet (< 10 mEq sodium/day) and again after 7 days of a liberal sodium diet (> 200 mEq sodium/day). Individuals who self-identified as Black with genotype data for both LSD1 gene (rs587168) and Striatin diplotype (rs888083 and rs6744560) were included. SSBP was defined as the change in systolic blood pressure on liberal sodium diet compared to restricted sodium diet. Results: 131 Black individuals were included in the analysis; 65 individuals carried a risk allele from both LSD1 and striatin genes (double risk) and 66 individuals lacked a risk allele from both genes (non-double risk). In multivariate analysis (correcting for site, hypertensive status, sex, age), SSBP was significantly higher among double risk compared to non-double risk individuals (17.9 +/- 13.4 mmHg vs 10.4 +/- 11.1 mmHg, p-value < 0.0001). Among hypertensive individuals (n=89), SSBP was 22.2 +/- 13.8 mmHg vs 11.9 +/- 11.3 mmHg for double risk vs non-double risk groups, respectively (p-value 0.0001). Conclusion: We demonstrated that individuals with risk alleles from both LSD1 and striatin exhibited a more severe form of SSBP. Given that striatin and LSD1 protein are involved in the same volume homeostatic pathway, our findings suggest there may be important interactions between these proteins. Further, a mineralocorticoid receptor blocker may be particularly effective in treating elevated blood pressure in these individuals. Presentation: 6/3/2024