Associations of Genetic Variations in the <i>NR3C2</i> With Salt Sensitivity, Longitudinal Blood Pressure Changes, and Incidence of Hypertension in Chinese Adults

Nuclear receptor subfamily 3 group C member 2 (NR3C2) encodes the mineralocorticoid receptor (MR), which plays a pivotal role in the regulation of electrolyte and fluid homeostasis by mediating the physiological actions of mineralocorticoids, primarily aldosterone. In this study, we analyzed data from the Baoji Salt-Sensitivity Study, a population-based dietary intervention conducted in 2004 in northern China. A total of 514 adults from 124 families were enrolled and underwent a controlled salt intake protocol consisting of a 3-day baseline diet, followed by sequential 7-day low-salt (3.0 g/day) and high-salt (18.0 g/day) phases. Participants were prospectively followed for 14 years to evaluate the long-term incidence of hypertension. Our results demonstrated a significant negative association between the NR3C2 single nucleotide polymorphism (SNP) rs5522 and pulse pressure (PP) response during the low-salt intervention. During the high-salt phase, rs5522 was significantly associated with systolic blood pressure (SBP), while SNP rs3910053 showed significant negative correlations with SBP, diastolic blood pressure (DBP), and mean arterial pressure (MAP). Furthermore, rs3910053 was significantly associated with the incidence of hypertension over 14 years. These findings highlight the important role of NR3C2 in salt sensitivity (SS) and the risk of developing hypertension in the Chinese population. Trial Registration: ClinicalTrials.gov. registration number: NCT02734472.