Association of Circulating Biomarkers of lnc-IGSF3-1:1, SCOC-AS1, and SLC8A1-AS1 with Salt Sensitivity of Blood Pressure in Chinese Population

Genome-wide association studies suggest that there is a significant genetic susceptibility to salt sensitivity of blood pressure (SSBP), but it still needs to be verified in varied and large sample populations. We attempted to verify the associations between single-nucleotide polymorphisms (SNPs) in candidate genes and SSBP and to estimate their interaction with potential risk factors. A total of 29 candidate SNPs were genotyped in the 2,057 northern Han Chinese population from the Systems Epidemiology Study on Salt Sensitivity. A modified Sullivan’s acute oral saline load and diuresis shrinkage test (MSAOSL-DST) was used to identify SSBP. A generalized linear model was conducted to analyze the association between SNPs and SSBP, and Bonferroni correction was used for multiple testing. Mediation analysis was utilized to explore the mediation effect of risk factors. Eleven SNPs in eight genes (PRKG1, CYBA, BCAT1, SLC8A1, AGTR1, SELE, CYP4A11, and VSNL1) were identified to be significantly associated with one or more SSBP phenotypes (P < 0.05). Four SNPs (PRKG1/rs1904694 and rs7897633, CYP4A11/rs1126742, and CYBA/rs4673) were still significantly associated after Bonferroni correction (P < 0.0007) adjusted for age, sex, fasting blood glucose, total cholesterol, salt-eating habit, physical activity, and hypertension. Stratified analysis showed that CYBA/rs4673 was significantly associated with SSBP in hypertensive subjects (P < 0.0015) and CYP4A11/rs1126742 was significantly associated with SSBP in normotensive subjects (P < 0.0015). Subjects carrying both CYBA/rs4673-AA and AGTR1/rs2638360-GG alleles have a higher genetic predisposition to salt sensitivity due to the potential gene co-expression interaction. Expression quantitative trait loci analysis (eQTL) suggested that the above positive four SNPs showed cis-eQTL effects on the gene expression levels. Mediation analysis suggested that several risk factors were mediators of the relation between SNP and SSBP. This study suggests that the genetic variants in eight genes might contribute to the susceptibility to SSBP, and other risk factors may be the mediators.

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Faculty Opinions recommendation of Increased salt sensitivity of ambulatory blood pressure in women with a history of severe preeclampsia.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.718087164.793489124 ◽

2014 ◽

Author(s):

Richard P Sloan ◽

Julie Spicer

Keyword(s):

Blood Pressure ◽

Ambulatory Blood Pressure ◽

Salt Sensitivity ◽

Severe Preeclampsia ◽

History Of

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Salt sensitivity in middle-aged population with normal blood pressure and method for determining salt sensitivity

Academic Journal of Second Military Medical University ◽

10.3724/sp.j.1008.2012.00747 ◽

2013 ◽

Vol 32 (7) ◽

pp. 747-749

Author(s):

Fei-zhou HAN ◽

Zheng WANG ◽

Yan-ping DING ◽

Qian WANG ◽

Hong-ling LIN

Keyword(s):

Blood Pressure ◽

Salt Sensitivity ◽

Normal Blood ◽

Normal Blood Pressure ◽

Middle Aged ◽

Aged Population

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Urinary sodium excretion and the risk of cardiovascular disease: A community-based cohort study in Taiwan

British Journal Of Nutrition ◽

10.1017/s0007114521001768 ◽

2021 ◽

pp. 1-42

Author(s):

Yi-Jie Wang ◽

Kuo-Lioug Chien ◽

Hsiu-Ching Hsu ◽

Hung-Ju Lin ◽

Ta-Chen Su ◽

...

Keyword(s):

Blood Pressure ◽

Metabolic Syndrome ◽

Systolic Blood Pressure ◽

Sodium Excretion ◽

Urinary Sodium Excretion ◽

Salt Sensitivity ◽

Urinary Sodium ◽

Mediating Effect ◽

Cvd Risk ◽

Media Thickness

Abstract Urinary sodium excretion is a potential risk factor for cardiovascular diseases (CVD). However, the underlying biological mechanisms and effects of salt sensitivity are unclear. The purpose of this study was to characterize the relative contribution of biological factors to the sodium-CVD association. A total of 2112 participants were enrolled in this study. Structured questionnaires and blood and urine samples were obtained. Twenty-four-hour sodium excretion was estimated using a single overnight urine sample. Hypertension, metabolic syndrome, and overweight status were considered to indicate salt sensitivity. Cox proportional hazard models were used to investigate the effects of salt sensitivity on urinary sodium excretion and CVD risk. The traditional mediation approach was used to calculate the proportion of mediation. The mean age (standard deviation) of the 2112 participants was 54.5 (12.2) years, and they were followed up for a mean of 14.1 [8.1] years. Compared with those in the lowest quartile, the highest baseline urinary sodium excretion (>4.2g/24 hours) was associated with a 43% higher CVD risk (hazard ratio, 1.43; 95% confidence interval, 1.02-1.99). Participants with high urinary sodium excretion, hypertension, or metabolic syndrome had a significantly high risk of CVD. The carotid intima-media thickness had the largest mediating effect (accounting for 35% of the sodium-CVD association), followed by systolic blood pressure (33%), left ventricular mass (28%), and diastolic blood pressure (14%). Higher urinary sodium excretion increased the risk of CVD, which was explained largely by carotid media-thickness and systolic blood pressure.

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The albumin-to-alkaline phosphatase ratio as an independent predictor of future non-alcoholic fatty liver disease in a 5-year longitudinal cohort study of a non-obese Chinese population

Lipids in Health and Disease ◽

10.1186/s12944-021-01479-9 ◽

2021 ◽

Vol 20 (1) ◽

Author(s):

Guotai Sheng ◽

Nan Peng ◽

Chong Hu ◽

Ling Zhong ◽

Mingchun Zhong ◽

...

Keyword(s):

Risk Factors ◽

Blood Pressure ◽

Fatty Liver Disease ◽

Chinese Population ◽

Independent Predictor ◽

Multiple Regression Model ◽

Obese People ◽

Alcoholic Fatty Liver ◽

Obese Subjects ◽

Alcoholic Fatty Liver Disease

Abstract Background The albumin-to-alkaline phosphatase ratio (AAPR) is a newly developed index of liver function, but its association in patients with non-alcoholic fatty liver disease (NAFLD) has not been established. The aim of this study was to investigate the association between the AAPR and NAFLD in a non-obese Chinese population. Methods The study included 10,749 non-obese subjects without NAFLD at baseline and divided them into quintiles according to the AAPR. A Cox multiple regression model was used to examine the association between the AAPR and its quintiles and the incidence of NAFLD. Results The average age of the study population was 43.65 ± 15.15 years old. During the 5-year follow-up, 1860 non-obese subjects had NAFLD events. In the Cox multiple regression model, after adjusting the model according to important risk factors, the AAPR and NAFLD risk were independently correlated, and with a gradual increase in the AAPR, the NAFLD risk decreased gradually (HR: 0.61, 95% CI: 0.47, 0.81; P-trend< 0.0001). Additionally, there were significant interactions between the AAPR and BMI, blood pressure and lipids (P-interaction < 0.05). Stratified analysis showed that the risk of AAPR-related NAFLD decreased in people with normal blood pressure and lipid levels, while the risk of AAPR-related NAFLD increased abnormally in people who were underweight. Conclusions This longitudinal cohort study provides the first evidence that the AAPR is an independent predictor of future NAFLD events in non-obese people. For non-obese people with a low AAPR, especially those with BMI < 18.5 kg/m2, more attention should be given to the management of risk factors for NAFLD to prevent future NAFLD.

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Abstract 101: Tissue-specific Deletion of Collectrin in the Proximal Tubular Epithelium Increases Arterial Pressure and Augments Salt-sensitivity

Hypertension ◽

10.1161/hyp.70.suppl_1.101 ◽

2017 ◽

Vol 70 (suppl_1) ◽

Author(s):

Sylvia Cechova ◽

Pei-Lun Chu ◽

Joseph C Gigliotti ◽

Fan Chan ◽

Thu H Le

Keyword(s):

Blood Pressure ◽

Blood Flow ◽

Renal Blood Flow ◽

Collecting Duct ◽

Critical Role ◽

Specific Effect ◽

Salt Sensitivity ◽

Kidney Cortex ◽

Mrna Levels ◽

Proximal Tubular

Background: Collectrin ( Tmem27 ) is a key regulator of blood pressure (BP) and modulator of the bioavailability of nitric oxide (NO) and superoxide. It is highly expressed in the kidney in the proximal tubule (PT), collecting duct, and throughout the vascular endothelium. We reported that collectrin plays a critical role as a chaperone for the reabsorption of all amino acids (AAs) in the PT, and for the uptake of the cationic AA L-arginine (L-Arg) in endothelial cells. Global collectrin knockout ( Tmem27 Y/- ) mice display baseline hypertension (HTN), augmented salt-sensitive hypertension (SSH), and decreased renal blood flow. Objective and Methods: To determine the PT-specific effect of collectrin on BP homeostasis and salt sensitivity, we used the Cre -loxP approach and PEPCK-Cre to generate a mouse line lacking collectrin specifically in the PT-- PEPCK-Cre + Tmem27 Y/Flox mice. PEPCK-Cre - Tmem27 Y/Flox mice were used as control. Radiotelemetry was used to measure BP for 2 weeks at baseline and 2 weeks on high salt diet (HSD). Renal blood flow at baseline and on HSD was measured using contrast enhanced ultrasound in the same mice. Results: Successful deletion of collectrin in the PT was confirmed by assessing mRNA levels using real-time RT-PCR, immunohistochemistry staining of renal tissues using anti-collectrin antibody, and quantitation of protein from kidney cortex by Western analysis. Compared to control PEPCK-Cre - Tmem27 Y/Flox mice (n=6), PEPCK-Cre + Tmem27 Y/Flox mice (n=6) displayed significantly higher systolic BP (SBP) at baseline (120.0 ± 2.5 vs 131.6 ± 2.9 mm Hg; p = 0.014) and after HSD (135.3 ± 2.6 vs 151.5 ± 5.2 mm Hg; p = 0.019). Renal blood flow was not different between groups, at baseline nor after HSD. Conclusion: Collectrin in the PT plays an important role in blood pressure homeostasis and response to sodium intake, independent of renal blood flow. Increasing proximal tubular collectrin activity may be a novel therapeutic strategy for the treatment of hypertension and salt-sensitivity.

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Renal denervation alters ambulatory blood pressure-derived salt sensitivity index in patients with uncontrolled hypertension

Journal of Hypertension ◽

10.1097/hjh.0000000000003050 ◽

2021 ◽

Vol Publish Ahead of Print ◽

Author(s):

Revathy Carnagarin ◽

Janis M. Nolde ◽

Rebecca Lee ◽

Leslie Marisol Lugo-Gavidia ◽

Natalie C. Ward ◽

...

Keyword(s):

Blood Pressure ◽

Ambulatory Blood Pressure ◽

Renal Denervation ◽

Salt Sensitivity ◽

Uncontrolled Hypertension ◽

Sensitivity Index

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Abstract P262: Resequencing Study Identifies Epithelial Sodium Channel Genes and Novel Low Frequency Variants Associated with Blood Pressure Salt-sensitivity: The GenSalt Study

Circulation ◽

10.1161/circ.133.suppl_1.p262 ◽

2016 ◽

Vol 133 (suppl_1) ◽

Author(s):

Christopher E Anderson ◽

Changwei Li ◽

Jiang He ◽

Dongfeng Gu ◽

Dabeeru C Rao ◽

...

Keyword(s):

Blood Pressure ◽

Family Structure ◽

Sodium Channel ◽

Association Studies ◽

Low Frequency ◽

Epithelial Sodium Channel ◽

Salt Sensitivity ◽

Minor Allele ◽

Indicator Variable ◽

High Sodium

Christopher E. Anderson, Changwei Li, Jiang He, Dongfeng Gu, Dabeeru C. Rao, James E. Hixson, Lawrence C. Shimmin, Jianfeng Huang, Charles C. Gu, Jichun Chen, Jianxin Li, Tanika N. Kelly Genetic association studies have identified significant associations between common variants from the epithelial sodium channel (ENaC) genes and blood pressure responses to dietary sodium interventions. The roles of low-frequency and rare ENaC variants in blood pressure salt-sensitivity remain largely unexplored. To test this hypothesis, we conducted an ENaC candidate gene resequencing study among participants in the Genetic Epidemiology Network of Salt-Sensitivity (GenSalt). The GenSalt study was conducted among 1,906 participants from 633 families who underwent a 7-day low-sodium (51.3 mmol sodium/day) followed by a 7-day high-sodium (307.8 mmol sodium/day) feeding-study. We chose the 300 GenSalt subjects with the highest and 300 GenSalt subjects with the lowest mean arterial pressure responses to the high sodium intervention to participate in the current resequencing study. Functional regions of three ENaC subunit genes ( SCNN1A , SCNN1B and SCNN1G ) were resequenced using the VariantSEQr TM system (Applied Biosystems; Foster City, CA). For gene-based analyses, variants with MAF less than 5% were first collapsed within each ENaC gene. The collapsed indicator variable was then tested for association with blood pressure salt-sensitivity using generalized estimating equations (GEE) to accommodate correlation of genotypes due to family structure and adjust for the fixed effects of age, gender and field center. Single variant analyses were performed for all low-frequency variants with a minor allele frequency (MAF) greater than 1% and less than 5%, again using GEE to accommodate family structure and adjust for covariables. We did not identify any associations between ENaC genes and blood pressure salt-sensitivity in the gene-based analyses. However, single variant analysis identified a novel association between a low-frequency variant in SCNN1G , rs148083677, and blood pressure salt-sensitivity (P=0.02). Each minor allele was associated with 71% lower odds of blood pressure salt-sensitivity. Although replication studies are needed, these findings provide promising evidence of a role for low-frequency ENaC variants in blood pressure salt-sensitivity.

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