Hypertension and Genetics: Why the DASH Diet Doesn't Work for Everyone

The DASH diet is one of the most thoroughly studied approaches to lowering blood pressure: less salt, less saturated fat, more vegetables and whole grains. But in practice, this approach does not work the same way for everyone.

In some people, lowering dietary sodium is genuinely accompanied by a reduction in blood pressure. Others may notice no meaningful change even with substantial dietary restriction (Maaliki et al., Frontiers in Physiology, 2022).

This difference may relate to individual variability in how the body responds to salt — determined by a combination of biological mechanisms, including genetically regulated features of blood pressure control.

Why the Body Responds to Salt Differently: The Underlying Mechanism

The renin-angiotensin-aldosterone system (RAAS) governs fluid-salt balance and blood pressure regulation in the body. In simple terms: after salt intake, the kidneys sense a change in fluid volume → produce renin → this triggers a chain of reactions → ultimately aldosterone is produced → the kidneys retain sodium and water → pressure rises. Under normal conditions, this system self-balances: when fluid volume is sufficient, aldosterone falls and sodium is excreted.

Research shows that in salt-sensitive individuals this balance is disrupted because the RAAS response to changes in dietary salt is blunted or abnormal: renin does not rise adequately when salt is restricted, nor fall when it is in excess. Sodium accumulates, but the system "fails to notice" the problem. Genetic variants in several genes of this system directly influence the likelihood of salt sensitivity (Maaliki et al., Frontiers in Physiology, 2022). Among them:

SGK1 gene (serum and glucocorticoid-regulated kinase 1)

This gene encodes a kinase that regulates the epithelial sodium channel (ENaC) in the distal tubules of the kidney. ENaC is the key "gateway" for sodium reabsorption. Variants of SGK1 are associated with elevated activity of this channel: sodium is retained longer than necessary, even with modest increases in salt intake. SGK1 acts as an amplifier of the aldosterone signal: in carriers of the risk variant rs2758151, aldosterone acts more "loudly" — and sodium reabsorption increases disproportionately (Haas et al., Hypertension, 2021).

WNK1 gene (With-No-Lysine kinase 1)

Another regulator of sodium transport in the distal tubules. Variants of WNK1 influence NCC transporter activity and determine how aggressively the kidney retains sodium. Elevated activity along this pathway is one mechanism of salt-dependent blood pressure elevation not directly linked to RAAS. A review of the genetic mechanisms of salt-sensitive hypertension describes the role of WNK1 variants as one of the key pathways of renal sodium retention (Maaliki et al., Frontiers in Physiology, 2022).

ACE gene (angiotensin-converting enzyme)

The ACE gene encodes the enzyme that converts angiotensin I into angiotensin II — a potent vasoconstrictor, i.e. a peptide that narrows blood vessels and directly raises blood pressure. Variants of this gene influence baseline enzyme activity and determine how actively RAAS maintains vascular tone and sodium retention. ACE polymorphisms are among the most well-studied genetic determinants of blood pressure (Padmanabhan & Dominiczak, Nat Rev Cardiol, 2021).

A systematic review of the genetics of salt sensitivity (Maaliki et al., Frontiers in Physiology, 2022) confirms: different genetic variants across the RAAS, the sympathetic nervous regulation system, and renal sodium transport genes collectively shape the physiological portrait of a salt-sensitive individual. This explains why salt sensitivity cannot be reliably identified through diet alone or standard blood tests: it is linked to the genetic architecture of blood pressure physiology.

What the Largest Hypertension Study Found

In 2024, the largest GWAS meta-analysis of blood pressure to date was published (Keaton et al., Nature Genetics, 2024). It pooled data from over one million individuals of European ancestry. Researchers identified more than 2,000 genetic loci associated with blood pressure measures, including 113 previously unknown. Among the new findings were loci in genes linked to iron metabolism and adrenergic receptors.

The main practical result: based on these data, a Polygenic Risk Score (PRS) was developed that enables assessment of genetic predisposition to hypertension. People with the highest genetic risk by this measure were seven times more likely to have clinically confirmed hypertension compared to those with low genetic risk (Keaton et al., Nature Genetics, 2024). This confirms that hypertension is a polygenic condition. Individual gene variants explain only a small fraction of risk. But a cumulative genetic profile can now identify elevated hereditary predisposition more precisely — before blood pressure has crossed a diagnostic threshold.

What This Means for Blood Pressure Management

If a person follows recommendations but their blood pressure does not respond to dietary changes, this does not always mean a mistake was made in counting salt — or that the person is insufficiently disciplined in following their doctor's advice. It may mean that the mechanism driving that person's elevated pressure requires a personalized rather than a standard approach.

For salt-resistant people with hypertension, salt restriction may produce little effect, while regular physical activity or weight reduction can improve outcomes. For salt-sensitive individuals, conversely, even a moderate increase in dietary salt can substantially worsen the situation (Maaliki et al., Front Physiol, 2022).

What may support better outcomes in people with a genetic predisposition to elevated blood pressure:

• Regular BP monitoring to catch trends early — not once a year at a checkup, but at least monthly in a calm setting.

• Managing risk factors — body weight, stress levels, physical activity, sleep quality: genetic predisposition does not cancel their importance, but may change their relative priority.

• Understanding salt's effect on your body: with a salt-sensitive predisposition, even an "ordinary" amount of salt in the daily diet may be excessive.

• Evaluating family history: hypertension in parents or siblings before age 55 is a meaningful signal to examine individual genetic characteristics.

• Timely cardiology consultation, especially when several risk factors are present simultaneously.

What a Genetic Test Analyzes and Why Knowing in Advance Matters

A genetic test does not determine whether a person has hypertension. Instead, it analyzes genetic features that may influence blood pressure regulation throughout life and, as a consequence, predisposition to hypertension. These are different things: the first is a clinical fact, the second is context for medical decisions.

The DNA test "Cardiovascular System" from Apixmed Prism covers three groups of genetic indicators:

• Cardiovascular diseases — genetic factors associated with risk of hypertension, myocardial infarction and ischemic heart disease, stroke, arrhythmias (including atrial fibrillation), aneurysm, and varicose veins.

• Metabolic risks — genetic variants linked to salt sensitivity (the effect of salt intake on blood pressure), non-alcoholic fatty liver disease, gout, and aerobic capacity and VO₂max.

• Lipids and inflammatory markers — genetic factors associated with levels of total cholesterol and HDL, apolipoprotein A1, homocysteine, C-reactive protein, and indicators of glucose and lipid metabolism disorders.

This information reflects not the current state of health but genetically determined predispositions and risks — to be considered alongside clinical data and lifestyle factors.

Blood Pressure and Genetics: Two Sides of the Same Problem

Diet and lifestyle remain the foundation of blood pressure management. But the answer to "why isn't it working for me" often lies not in the diet itself, but in how the blood pressure regulation system is organized at the genetic level. Genetics does not eliminate the need for effort. But it provides a context in which those efforts can be more effective.

A person who knows their genetic characteristics comes to the cardiologist not with the question "what is wrong," but with a specific request: given these hereditary predispositions, what approach makes most sense? This changes the quality of the conversation — and of the decisions that follow.

This material is informational and does not constitute medical advice. Blood pressure depends on many factors, including age, lifestyle, comorbidities, and heredity. Genetic test results are not a diagnosis and do not replace a physician's consultation. The Apixmed Prism report provides genetic context that complements examination results and supports decision-making together with a doctor.

References

• Keaton JM, et al. Genome-wide analysis in over 1 million individuals of European ancestry yields improved polygenic risk scores for blood pressure traits. Nat Genet. 2024;56(5):778–791. https://doi.org/10.1038/s41588-024-01714-w

• Maaliki D, Itani MM, Itani HA. Pathophysiology and genetics of salt-sensitive hypertension. Front Physiol. 2022;13:1001434. https://doi.org/10.3389/fphys.2022.1001434

• Padmanabhan S, Dominiczak AF. Genomics of hypertension: the road to precision medicine. Nat Rev Cardiol. 2021;18(4):235–250. https://doi.org/10.1038/s41569-020-00466-4

• Haas AV, Yee LE, Yuan YE, et al. Genetic predictors of salt sensitivity of blood pressure: the additive impact of 2 hits in the same biological pathway. Hypertension. 2021;78(6):1809–1817. https://doi.org/10.1161/HYPERTENSIONAHA.121.18033

• Elijovich F, et al. Salt sensitivity of blood pressure: a scientific statement from the American Heart Association. Hypertension. 2016;68:e7–e46. https://doi.org/10.1161/HYP.0000000000000047