Abstract
Objectives Genome-wide association studies and candidate gene studies have found many single nucleotide polymorphisms (SNPs) that affect salt sensitivity (SS). We constructed a polygenic risk score (PRS) to estimate the joint effect of these SNPs on SS. Methods We recruited 762 Chinese participants into the study. An unweighted PRS was constructed using 42 known genetic risk variants associated with SS or salt sensitivity blood pressure. A modified Sullivan's acute oral saline load and diuresis shrinkage test was used to detect salt sensitivity. Logistic regression was used to estimate the joint effect of the SNPs on SS both overall and after stratification by hypertension. Results The mean age of the participants was 57.1 years, and most of them were female (77.4%). The prevalence of SS was 28.7%. Both the continuous PRS and PRS tertiles were significantly associated with the risk of SS and a BP increase of more than 5 mmHg during acute salt loading but were not associated with a BP decrease of more than 10 mmHg during the diuresis shrinkage process. In the normotensive group, participants with PRSs in the middle and top tertiles had a more than twofold increased risk of SS (OR = 2.18, 95% CI: 1.15–4.12, P = 0.016, and OR = 2.28, 95% CI: 1.19–4.38, P = 0.016, and OR = 2.28, 95% CI: 1.19–4.38, P = 0.016, and OR = 2.28, 95% CI: 1.19–4.38, P = 0.016, and OR = 2.28, 95% CI: 1.19–4.38, Conclusion The 42 investigated SNPs were jointly and significantly associated with SS, especially in the normotensive Chinese population. These findings may provide genetic evidence for identifying target populations that would benefit from salt restriction policies.
Highlights
Salt sensitivity of blood pressure (SSBP) is characterized as individual heterogeneity of the blood pressure (BP) response to salt intake
The polygenic risk score (PRS) was significantly associated with salt sensitivity in the normotensive population, and this association was robust to adjustment for potential confounders
Our study is one of the few to investigate the joint effect of BP loci on salt sensitivity, which could provide evidence of a high-risk population when implementing salt restriction strategies
Summary
Salt sensitivity of blood pressure (SSBP) is characterized as individual heterogeneity of the blood pressure (BP) response to salt intake. Genome-wide association studies (GWAS) and candidate gene studies found evidence of an association between genes of other pathways, including a polymorphism of ENaC subunits in ion and water channels [5], an NAD(P)H oxidase p22phox gene C242T polymorphism in the endothelial system [6], a beta-2 adrenergic receptor diplotype in the sympathetic nervous system [7], and SSBP. In these previous studies, each SNP only contributed a minor effect on the blood pressure response in salt loading/depletion, and the results were inconsistent. Evidence regarding the association between the PRS and salt sensitivity remains limited, and the results are inconsistent (see below)
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