Striatin Genotype and Its Association with Salt-Sensitivity of Blood Pressure
Presentation Number: SUN 531
Date of Presentation: April 2nd, 2017
Tina Gupta*1, Molly Connors2, Jiawei Tan2, Noha Ahmed2, Gail K. Adler1, Luminita H Pojoga1, Tham Yao1, Amanda Elizabeth Garza1, Jonathan S Williams3, Jose R Romero1 and Gordon H Williams1
1Brigham and Women's Hospital, Harvard Medical School, Boston, MA, 2Brigham and Women's Hospital, 3Brigham & Women's Hospital, Harvard Medical School, Boston, MA
Striatin Genotype and its Association with Salt-Sensitivity of Blood Pressure
Gupta T, Connors M, Tan JW, Ahmed N, Adler GK, Pojoga LH, Yao T, Garza AE, Williams JS, Romero JR, Williams GH
Division of Endocrinology, Diabetes, and Hypertension, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA
Abstract: Investigation of the relationship between genotype and blood pressure (BP) is vital to understanding and addressing limitations to our current approach to hypertension (HTN) treatment. This study focused on newly identified associations between striatin (STRN) and three factors: aldosterone (ALDO)’s mechanisms of action/secretion, vascular function and salt intake. In pre-clinical studies, we documented that salt intake modifies vascular function, ALDO secretion and the level of the cytosolic scaffolding protein STRN. These facts led us to hypothesize that polymorphic variants in the STRN gene would be associated with salt sensitivity of blood pressure (SSBP) and hypertension (HTN). We studied 718 individuals from the HyperPATH Cohort with no known cardiovascular (CV) or other major diseases except that some participants had mild to moderate HTN and/or diabetes.. Subjects were genotyped at SNP rs2540923 and were studied after one-week of a liberal salt (200 mmol Na+/day) and one-week of a low salt (10 mmol Na+/day) diet. On each diet, BP, ALDO, cortisol, plasma renin activity (PRA) and catecholamines were measured. Linear regression analyses adjusted for race, sex, disease state (HTN or diabetes), age and body mass index were performed. Minor allele carriers had significantly greater SSBP than non-carriers (p = 0.004). This difference persisted in all subcategories: hypertensives, normotensives, older, younger, African, Caucasian, male or female. Of potential mechanistic interest, we observed significantly lower plasma epinephrine levels in risk allele carriers than non-carriers (p = 0.014). These results suggest that the striatin risk allele status could be useful in directing personalized medicine to specific individuals for targeted treatment. Furthermore, given that normotensive risk allele carriers also had greater SSBP, this risk allele may identify at risk individuals in the pre-hypertensive state for preventive therapy. Finally, our findings underscore the heritability of SSBP.
Nothing to Disclose: No disclosures for any of the authors.
Sources of Research Support: NIH RO1 HL114765, NIH K24 HL103845 and NIH T32 HL007609
Nothing to Disclose: TG, MC, JT, NA, GKA, LHP, TY, AEG, JSW, JRR, GHW