Genetically, Dietary Sodium Intake Is Causally Associated with Salt-Sensitive Hypertension Risk in a Community-Based Cohort Study: a Mendelian Randomization Approach

Abstract

Purpose of Review

Excessive dietary salt intake is associated with an increased risk of hypertension. Salt sensitivity, i.e., an elevation in blood pressure in response to high dietary salt intake, has been associated with a high risk of cardiovascular disease and mortality. We investigated whether a causal association exists between dietary sodium intake and hypertension risk using Mendelian randomization (MR).

Recent Findings

We performed an MR study using data from a large genome-wide association study comprising 15,034 Korean adults in a community-based cohort study. A total of 1282 candidate single nucleotide polymorphisms associated with dietary sodium intake, such as rs2960306, rs4343, and rs1937671, were selected as instrumental variables. The inverse variance weighted method was used to assess the evidence for causality. Higher dietary sodium intake was associated with salt-sensitive hypertension risk. The variants of SLC8E1 rs2241543 and ADD1 rs16843589 were strongly associated with increased blood pressure. In the logistic regression model, after adjusting for age, gender, smoking, drinking, exercise, and body mass index, the GRK4 rs2960306TT genotype was inversely associated with hypertension risk (OR, 0.356; 95% CI, 0.236–0.476). However, the 2350GG genotype (ACE rs4343) exhibited a 2.11-fold increased hypertension risk (OR, 2.114; 95% CI, 2.004–2.224) relative to carriers of the 2350AA genotype, after adjusting for confounders. MR analysis revealed that the odds ratio for hypertension per 1 mg/day increment of dietary sodium intake was 2.24 in participants with the PRKG1 rs12414562 AA genotype.

Summary

Our findings suggest that dietary sodium intake may be causally associated with hypertension risk.

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Abbreviations

MR:

Mendelian randomization approach

SNP:

Single nucleotide polymorphism

BMI:

Body mass index

SBP:

Systolic blood pressure

DBP:

Diastolic blood pressure

LDL:

Low-density lipoprotein cholesterol

HDL:

High-density lipoprotein cholesterol

TG:

Triglycerides

IVW:

Inverse-variance weighted method

ACE:

Angiotensin-converting enzyme

β2-AR:

β2-adrenergic receptor

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Funding

This study was supported, in part, by a grant from the Korea Center for Disease Control and Prevention (2005-E71013-00, 2006-E71002-00, 2007-E71013-00, 2008-E71004-00, 2009-E71006-00, 2010-E71003-00). This research was supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF), funded by the Ministry of Education (2017R1D1A3B03034119, 2014M3C9A3064552), and the KRIBB Initiative program. This research was also supported by the Medical Research Center Program (2017R1A5A2015369). Furthermore, this work was supported (in part) by the Yonsei University Research Fund 2017. Bioresources for this study were provided by the National Biobank of Korea and the Centers for Disease Control and Prevention, Republic of Korea (2017-009).

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The authors’ responsibilities were as follows—SBK and JRC acquired the data and designed and conducted the research; SJ and JRC analyzed the data and drafted the manuscript; SJ, NK, and JRC analyzed the data and had primary responsibility for final content; J-Y K and YC critically revised the manuscript for important intellectual content; and all authors read and approved the final manuscript. The other authors report no conflicts of interest.

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Correspondence to Namshin Kim or Jung Ran Choi.

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This article is part of the Topical Collection on Nutrition and Hypertension

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Jeong, S., Kim, J., Cho, Y. et al. Genetically, Dietary Sodium Intake Is Causally Associated with Salt-Sensitive Hypertension Risk in a Community-Based Cohort Study: a Mendelian Randomization Approach. Curr Hypertens Rep 22, 45 (2020). https://doi.org/10.1007/s11906-020-01050-4

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Keywords

  • Sodium intake
  • Hypertension
  • Mendelian randomization approach
  • Community-based cohort study