A candidate locus in the renalase gene and susceptibility to blood pressure responses to the dietary salt

Abstract

Background: High dietary salt confers a risk of elevating blood pressure (BP) and the development of hypertension. BP to salt intake may be determined in part by individual genetic predisposition. Identifying these genetic underpinnings will enhance our understanding of the biological mechanisms of BP regulation. This study aims to assess the genetic association with salt sensitivity of BP (SSBP) within two well-phenotyped multinational cohorts. Methods: A total of 720 white participants from the HyperPATH consortium program were selected and genotyped using a multiethnic genotyping array. Individuals consumed two study diets containing high (>200 mEq/day) and low (<10 mEq/day) sodium content, after which SSBP, aldosterone, and plasma renin activity (PRA) were assessed in a controlled inpatient research setting. Results: A top signal (rs10887801; beta = 4.57, P = 5.03E − 07) at the renalase gene ( RNLS ) region was significantly associated with SSBP. We also identified seven single nucleotide variants with linkage disequilibrium to the top signal at this region that comprised a significant haplotype (TCTTAGTT, P = 0.00081). Homozygous carriers of the T-risk allele of the key single nucleotide variant had higher SSBP ( P ≤ 0.00001) and lower PRA ( P = 0.0076) compared with the nonrisk allele. Conclusion: We identified significant associations between genetic variants of the RNLS gene and BP responses to dietary salt intervention and PRA that suggest susceptibility to volume-driven hypertension. These findings may contribute to a better understanding of the genetic mechanisms underlying BP regulation, support the role of RNLS in the pathogenesis of SSBP, and identify individuals who may be at risk from excess dietary salt intake.

Enhancing Genetic Association Power in Endometriosis through Unsupervised Clustering of Clinical Subtypes Identified from Electronic Health Records

“…It was the only significant association with the cardiometabolic cluster. RNLS is highly expressed in the heart and contributes to regulating blood pressure (43). In genetic association studies, RNLS has been previously associated with type 1 diabetes (44) and smoking initiation (45).…”

Research progress of autoimmune diseases based on induced pluripotent stem cells

“…confirmed RNLS as a potential target for β cell protection in T1D, aiming to mitigate immune recognition of β cells ( 63 ). RNLS, responsible for degrading circulating catecholamines and regulating blood pressure ( 152 ), was first discovered as a susceptible factor in autoimmune destruction of pancreatic β cells through a GWAS study of monocytes, including their derivatives, such as macrophages and dendritic cells, from T1D patients ( 153 ). Cai et al.’s study demonstrated that RNLS deletion did not affect the ability of iPSCs into β cells and secrete insulin ( 63 ).…”

Coexistence of Cardiovascular Risk Factors and Blood Renalase Concentration

“…In human studies, by selecting 720 participants from the HyperPATH consortium program and genotyping with the use of a multiethnic genotyping array of their renalase (RNLS) gene, the research group of Heydarpour et al determined that certain genetic variants of the RNLS gene associated with salt sensitivity of blood pressure and responded to dietary salt intervention [42]. Many other studies also confirm a decrease in blood renalase concentration caused by the influence of a high-salt diet [43][44][45].…”