Associations of genetic variations in NEDD4L with salt sensitivity, blood pressure changes and hypertension incidence in Chinese adults

Abstract

Neural precursor cell expressed developmentally downregulated 4-like (NEDD4L), a member of the E3 ubiquitin-protein ligases, encoded by NEDD4L gene, was found to be involved in in salt sensitivity by regulating sodium reabsorption in salt-sensitive rats. The authors aimed to explore the associations of NEDD4L genetic variants with salt sensitivity, blood pressure (BP) changes and hypertension incidence in Chinese adults. Participants from 124 families in Northern China in the Baoji Salt-Sensitive Study Cohort in 2004, who received the chronic salt intake intervention, including a 7-day low-salt diet (3.0 g/day) and a 7-day high-salt diet (18 g/day), were analyzed. Besides, the development of hypertension over 14 years was evaluated. NEDD4L single nucleotide polymorphism (SNP) rs74408486 was shown to be significantly associated with systolic BP (SBP), diastolic BP (DBP) and mean arterial pressure (MAP) responses to low-salt diet, while SNPs rs292449 and rs2288775 were significantly associated with pulse pressure (PP) response to high-salt diet. In addition, SNP rs4149605, rs73450471, and rs482805 were significantly associated with the longitudinal changes in SBP, DBP, MAP, or PP at 14 years of follow-up. SNP rs292449 was significantly associated with hypertension incidence over the 14-year follow-up. Finally, this gene-based analysis found that NEDD4L was significantly associated with longitudinal BP changes and the incidence of hypertension over the 14-year follow-up. This study indicated that gene polymorphism in NEDD4L serve an important function in salt sensitivity, longitudinal BP change and development of hypertension in the Chinese population.

Trial registration: ClinicalTrials.gov NCT02734472.

Keywords: NEDD4L; gene polymorphism; hypertension; salt; salt sensitivity.