Associations of plasma uromodulin and genetic variants with blood pressure responses to dietary salt interventions

Abstract

Uromodulin, also named Tamm Horsfall protein, have been associated with renal function and sodium homeostasis regulation. The authors sought to examine the effects of salt intake on plasma and urinary uromodulin levels and the association of its genetic variants with salt sensitivity in Chinese adults. Eighty patients from our natural population cohort were maintained sequentially either on a usual diet for 3 days, a low-salt diet (3.0 g) for 7 days, and a high-salt diet (18.0 g) for an additional 7 days. In addition, the authors studied 514 patients of the Baoji Salt-Sensitive Study, recruited from 124 families who received the same salt intake intervention, and investigated the association of genetic variations in uromodulin gene with salt sensitivity. Plasma uromodulin levels were significantly lower on a high-salt diet than on a baseline diet (28.3 ± 4.5 vs.54.9 ± 8.8 ng/ml). Daily urinary excretions of uromodulin were significantly decreased on a high-salt diet than on a low-salt diet (28.7 ± 6.7 vs. 157.2 ± 21.7 ng/ml). SNPs rs7193058 and rs4997081 were associated with the diastolic blood pressure (DBP), mean arterial pressure (MAP) responses to the high-salt diet. In addition, several SNPs in the uromodulin gene were significantly associated with pulse pressure (PP) response to the low-salt intervention. This study shows that dietary salt intake affects plasma and urinary uromodulin levels and that uromodulin may play a role in the pathophysiological process of salt sensitivity in the Chinese populations.

Salt loading decreases urinary excretion and increases intracellular accumulation of uromodulin in stroke-prone spontaneously hypertensive rats

“…Retrospective analysis of the DASH-Sodium trial showed that higher urine UMOD levels were not associated with an increase in BP in response to an increase in salt intake [ 11 ]. Recently, an interventional study in a Chinese cohort showed that high salt intake reduced significantly both plasma and urinary UMOD levels [ 12 ].…”

Associations of Renalase With Blood Pressure and Hypertension in Chinese Adults

“…From April to November 2004, we established the cohort of Baoji Salt-Sensitive Study, which recruited 514 adults from 124 families in seven villages in Baoji city, Shaanxi, China. The detailed study design has been published previously ( 20 – 22 ). To identify the associations of potential genetic variants with longitudinal BP changes and the incidence of hypertension, we followed this cohort in 2009, 2012, and 2018.…”

“…From April to November 2004, we established the cohort of Baoji Salt-Sensitive Study, which recruited 514 adults from 124 families in seven villages in Baoji city, Shaanxi, China. The detailed study design has been published previously (20)(21)(22).…”

Evolving Concepts in Uromodulin Biology, Physiology, and Its Role in Disease: a Tale of Two Forms

“…This has been reviewed by Padmanabhan et al 46 . Single nucleotide polymorphism variants in the UMOD promoter area have been linked to risk of HTN, 47,48 but such association may be dependent on other factors, including ethnicity (single nucleotide polymorphism variants association with HTN may be different in patients of African descent compared with European or Chinese 49 ). Uromodulin regulation of salt handling, NKCC2 and NCC activity could be the link to HTN.…”