Genetic Predisposition and Salt Sensitivity in a Chinese Han Population: The EpiSS Study

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=0.013, respectively) compared with participants with PRSs in the first tertile. In the normotensive group, participants with PRSs in the middle tertile (OR = 1.94, 95% CI: 1.01-3.71, P=0.046) and top tertile (OR = 2.30, 95% CI: 1.19-4.44, P=0.013) had an increased risk of a greater than 5 mmHg increase in BP during acute salt loading than those with PRSs in the first tertile. In the hypertension group, neither the continuous PRS nor PRS tertile was significantly associated with the risk of SS. 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.