Just like how water exerts pressure on the walls of the pipes when flowing, blood too exerts pressure on the surface blood vessels.

The pressure exerted must be constant and of a particular value. A drop or hike in this pressure may likely be a warning of an abnormality.

When the pressure exerted by blood on the walls increases beyond a certain level, it is known as hypertension or high blood pressure.

Hypertension is a common health condition. Nearly half the American population is expected to be diagnosed with hypertension. 

Symptoms Of Hypertension

Most people don’t experience any particular symptom until the condition becomes severe. That is why hypertension is rightly known as the "silent killer”. Even when people do experience the symptoms, they are almost always associated with other issues.

What Are The Symptoms Of Hypertension?

What Causes Hypertension?

The causes of hypertension or high blood pressure are still being studied. Some of the well-accepted and scientifically proven causes are smoking, obesity or being overweight, diabetes, having a sedentary lifestyle (one involving very minimal physical activities), and unhealthy eating habits. 

When it comes to diet, a high salt intake can result in hypertension, especially if you are 'salt-sensitive.'

What Is Salt Sensitivity?

We all require some amount of salt in our diets to survive. As its chemical name sodium chloride suggests, salt contains an important mineral, sodium.

Salt sensitivity is a measure of how your blood pressure responds to salt intake. People are either salt-resistant - their blood pressure doesn't change much with salt intake or salt-sensitive - their blood pressure increases upon salt consumption.

About 60% of people with high blood pressure are thought to be salt-sensitive.

How To Determine If You Are Salt Sensitive?

If you suspect salt sensitivity, the best way forward is to approach your medical practitioner. 

Your practitioner may initially put you on a low sodium diet. This can then be switched to a high sodium diet. 

If there's a rise in the blood pressure by 5-10% after the switch, then you may be considered salt sensitive.

The Story Behind Salt Sensitivity

When our ancestors were roaming about in Africa, many thousands of years ago, salt may have been a scarce nutrient in their diets.

Our bodies require salt for a lot of important functions like muscle contraction, maintaining blood volume, and sending messages and signals between the cells.

Salt also plays a role in water retention in the body. In archaic times when our ancestors were out and about in the Savannah, exposed to the sun for long periods of time, being salt-sensitive would have given them an advantage by losing less water to the environment. 

Salt retention became even more essential when infectious diseases (which often cause people to lose sodium through diarrhea and vomiting) started to spread.

Researchers speculate that this is the reason why humans probably developed the sensitivity to salt. 

So, an ability to hold on to this nutrient was a survival advantage in many ways. 

Unfortunately for many of us, we have retained this evolutionary ability to hold on to calories and sodium ever so dearly. Being surrounded by an environment filled with high-salt and high-calorie foods has automatically ended up increasing our risk of obesity and hypertension. 

Surprisingly, salt is not only found in salty foods, but many sweet-tasting foods have large amounts of salt in them. Salt is used as a taste enhancer and a preservative.

Many brands that make cake and pastries hide some amount of salt in them in order to enhance the taste. 

ACE Gene, Salt (Sodium), And Blood Pressure Control - Molecular aspect

The kidneys control blood pressure by either excreting or reabsorbing sodium. Since sodium moves with water, it is excreted as urine when the blood pressure needs to be lowered. By contrast, the kidneys reabsorb sodium in order to increase the blood pressure.

Our blood pressure is also regulated by the widening and narrowing of the blood vessels to regulate the blood flow.

The ACE gene produces the angiotensin-converting enzyme and plays a key role in controlling blood pressure.  

Whenever there's a drop in the blood pressure, it triggers the release of a hormone, renin, from the kidneys. Renin helps form a molecule, angiotensin 1. Angiotensin 1 and 2 are two forms of the hormone angiotensin, that controls the narrowing of the blood vessels to regulate blood pressure. Angiotensin-converting enzyme or ACE, released by the lungs, converts angiotensin 1 to angiotensin 2. Angiotensin 2 triggers the release of another hormone, aldosterone, that helps kidneys reabsorb sodium and water, thereby increasing the blood pressure.

The Genetics Behind Salt Sensitivity and Blood Pressure

Some types of ACE gene increase the production of the angiotensin-converting enzyme. This results in an increased sodium absorption, thereby causing a higher than normal spike in the blood pressure. 

rs4343

The SNP rs4343 influences the production of the angiotensin-converting enzyme in response to sodium (salt) in blood. The A allele of rs4343 has been associated with increased blood pressure on high salt intake.

Food recommendations for salt-sensitivity

People who are salt sensitive should watch the sodium content in their diet. Foods that are low in sodium and high in potassium are recommended - potassium lessens the effect of sodium.

The DASH diet is popular among people with high blood pressure. This diet emphasizes fruits and vegetables - both of which are low in sodium and high in potassium. It also includes nuts, whole grains, poultry, and fish. 

Dairy products also are a good addition to the diet. Milk, yogurt, cheese, and other dairy products are major sources of calcium, vitamin D, and protein.

Other low sodium foods include basil, apples, cinnamon, brown rice, kidney beans, and pecans.

Summary

While retaining salt in the body was a survival advantage for our ancestors, the same has become a villain in this day and age of high-calorie and high-salt foods all around. Hypertension, characterized by a persistent elevation in the blood pressure, is a risk factor for many serious conditions like heart disease and stroke. Depending on our sensitivity to the sodium in salt, our blood pressure either spikes or lurks in the normal range upon consumption of salt. The ACE gene plays an important role in determining our sensitivity to salt. The ‘salt-sensitive’ individuals must be wary of the amount of sodium (salt) intake in order to maintain their blood pressure in the normal range. The DASH diet is popular among people who are trying to limit their salt intake.

References

  1. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3214830/
  2. https://pubmed.ncbi.nlm.nih.gov/11711524/
  3. https://en.wikipedia.org/wiki/Angiotensin
  4. https://www.healthline.com/nutrition/dash-diet

ACE gene: An introduction

ACE gene codes for Angiotensin-Converting Enzyme.

This enzyme is a part of the Renin-Angiotensin System, which is responsible for maintaining blood pressure, and fluid and salt balance in the body.

The enzyme cleaves the protein angiotensin I at a particular site, converting it into angiotensin II.

This angiotensin II brings about constriction of blood vessels, thereby increasing the blood pressure.

ACE gene is located on the long arm of chromosome 17.

Mutations in the ACE gene have been associated with a severe form of the renal disease called renal tubular dysgenesis.

What are ACE inhibitors? 

As the name goes, ACE inhibitors are medications that slow down or inhibit the effects of angiotensin-converting enzyme (ACE).

Such medications are involved in relaxing the blood vessels and reducing blood pressure levels.

They are primarily used as anti-hypertensive drugs.

The ACE inhibitors prevent the angiotensin-converting enzyme from producing angiotensin II.

This reduces blood pressure and makes it easier for the heart to pump blood, thereby improving the functioning of the heart.

ACE inhibitors can be used to treat the following conditions:

Common examples of ACE inhibitors are:

What are the side effects of ACE inhibitors? 

Like any other medication, ACE inhibitors too, have a few side effects. But, most of them are not a cause of worry.

These include:

ACE inhibitors and weight loss 

According to a study conducted by researchers in Australia, it was observed that ACE deficient mice weighed 20% lesser than the mice with ACE activity. It was also observed that the ACE deficient mice had 50% less body fat, especially around the belly area. 

The results from this study have suggested that ACE inhibitors might help in weight loss around the mid-section in humans.

This, along with the other effects of ACE inhibitors, might be cardio-protective.

Handpicked article for you: Is Dr. Rhonda Patrick Diet For You? Analyze Your DNA Raw Data To Find Out Your Nutritional Needs!

Are ACE inhibitors safe for the kidneys? 

ACE inhibitors are cardio and renoprotective.

They reduce systemic vascular resistance in patients with hypertension, chronic renal disease, and heart failure.

ACE inhibitors as we know by now cause a fall in the blood pressure.

Intrarenal efferent vasodilation is also observed along with a fall in the glomerular filtration pressure.

These events are said to be renoprotective.

However, when the glomerular filtration is critically dependent on the angiotensin II-mediated efferent vascular tone, giving ACE inhibitors to the patient can induce acute renal failure.

The systemic and renal hemodynamic consequences, both benefits and adverse effects, are brought about by the depletion of sodium. 

Treating such patients with diuretics and ACE inhibitors, along with some sodium intake restrictions, can improve their therapeutic efficiency.

So, if the patients have a high risk of adverse renal effects to ACE inhibitors, their dosages should be titrated appropriately, and renal function and potassium levels should be closely monitored.

ACE inhibitors vs. beta-blockers 

ACE inhibitors and beta-blockers are both classes of drugs that are used to treat hypertension.

Though their goal is the same, their mechanism of action is entirely different. 

ACE inhibitors work by preventing the conversion of angiotensin I to angiotensin II.

Thus, they cause the relaxation of blood vessels and lower the blood pressure.

Beta-blockers, on the other hand, block epinephrine (adrenaline) and norepinephrine (noradrenaline) from binding to beta receptors on the nerves.

This reduces the heart rate and subsequently lowers blood pressure.

Both these classes of drugs have their side effects and drawbacks.

In most cases, a combination of one or more anti-hypertensive drugs is used to treat high blood pressure.

What is hypertension? 

Hypertension is a widespread and highly prevalent lifestyle disease.

It is a medical term given for consistently high blood pressure over 120mm Hg systolic and 80mm Hg diastolic.

Hypertension is characterized by the flow of blood at high pressure against the walls of the blood vessels. 

As a result, the workload of the blood vessels and the heart increases substantially.

Over a period of time, this force and friction on these tissues end up damaging them, and this can precipitate many conditions.

Some of them include:

What are the leading causes and symptoms of hypertension? 

Hypertension can be of two types: Primary and secondary.

When the rise in blood pressure levels is due to a non-identifiable cause, it is known as primary hypertension.

However, when there is an increase in the blood pressure levels due to an underlying condition, it is called secondary hypertension.

Some common causes of hypertension include:

Though hypertension is often silent, in some cases, the patient does show some symptoms. Like:

What are the four stages of hypertension? 

[table id=124 /]

Individuals who are in the prehypertension stage can progress to the other stages if immediate action is not taken.

Untreated cases of hypertension can even be fatal.

Diet recommendations to reduce blood pressure

One of the primary causes that result in hypertension is poor lifestyle choices, which includes an unhealthy diet.

So, to reduce the blood pressure levels and maintain it under the limit, certain dietary recommendations should be followed.

What is the DASH diet? 

DASH diet is an acronym for Dietary Approaches to Hypertension diet.

The plan includes adopting a diet which includes fruits, vegetables, whole grains, low-fat dairy, nuts and seeds, legumes, fish, and poultry.

The most important aspect is to eat foods that are rich in potassium, calcium, magnesium, protein, and fiber and avoiding foods rich in sodium.

DASH diet is low salt and low sugar diet that does not allow the intake of desserts, sweetened drinks and beverages, red meat, and processed meats and fats.

The diet allows a maximum of 2000 calories a day, which includes:

  1. 7-8 servings of grains
  2. 4-5 servings each of fruits and vegetables
  3. 2-3 servings of low-fat or fat-free dairy products
  4. 1-2 servings of lean meat or fish 
  5. 4-5 servings of nuts and seeds per week
  6. 2-3 servings of oil or fat 
  7. Not more than five servings of sweets per week 

Can high blood pressure be cured?

In most cases of primary hypertension, blood pressure levels can be brought down by a combination of medications, dietary changes, regular exercise, and lifestyle modifications.

Once the blood pressure has been controlled, the individual can maintain his/her blood pressure levels within a reasonable range by living and eating healthy.

In many cases, a precautionary medication is advised to prevent the blood pressure from shooting up. 

Salt intake and high blood pressure 

Our kidneys are responsible for water and salt regulation.

More the salt we consume, more the kidneys tend to retain water.

The increased water retention results in an increase in our systemic blood pressure.

This leads to increased pressure on the walls of many blood vessels, which may result in organ damage. 

ACE gene and hypertension 

Of the many factors that can cause hypertension, the ACE gene also plays a role.

We know that the blood pressure in the body is controlled by the kidneys.

But, to be more specific, the Renin-Angiotensin System or RAS system is responsible for regulating it.

Some genetic variations are related to the RAS system, the most common one being the insertion/deletion polymorphism of the ACE gene.

So, essentially, the interactions between the ACE I/D polymorphism, sodium intake the RAS system determine your blood pressure and influence the risk of developing hypertension.

rs2106809

It was observed that the DD genotype of ACE and the TT genotype of ACE2 were significantly high in female hypertensives and the T allele of ACE2 was also linked to male hypertensives.

[table id=123 /]

rs4308

SNP rs4308 is located on chromosome 17.

Presence of the A allele is responsible for the increase in the diastolic blood pressure.

This SNP locus also features as a target of anti-hypertensive drugs.

ACE gene and fitness 

The ACE gene has been linked to athletic performance.

A genetic variation consisting of 287 DNA bases when inserted into the ACE gene causes a decrease in the ACE enzyme activity.

This version of the gene is called the ‘I’ version.

This variation is shown to be present in athletes, especially sprinters.

The presence of this insertion has been seen in many athletes who perform well in endurance sports such as wrestling, swimming, triathlons, etc.

Though the exact mechanism of how the ACE I gene contributes to fitness and athleticism is unknown, it probably has something to do with an increase in the heart rate, blood pressure, and muscle growth during training.

rs4343

SNP rs4343 of the ACE gene has the ‘A’ and ‘G’ allele.

The A allele is associated with the insertion or I variation, whereas the G allele of the gene is associated with deletion or the D variation.

The G allele results in an increased risk of heart disease (GG) whereas, the minor A allele shows an increased association with endurance-based athletes. 

SNP rs4343 has also recently been linked to susceptibility to migraine, where a G/G polymorphism was seen in patients with migraine with aura as compared to patients of migraine without aura.

Does your 23andme, Ancestry DNA, FTDNA raw data have ACE gene variant information?

CHIP VersionVDR SNPs
23andMe (Use your 23andme raw data to know your ACE Variant)
v1 23andmePresent
v2 23andmePresent
v3 23andmePresent
v4 23andmePresent
V5 23andme (current chip)Present
AncestryDNA  (Use your ancestry DNA raw data to know your ACE Variant)
v1 ancestry DNAPresent
V2 ancestry DNA (current chip)Present
Family Tree DNA  (Use your FTDNA raw data to know your ACE Variant)
OmniExpress microarray chipPresent

References:

  1. https://ghr.nlm.nih.gov/gene/ACE#synonyms
  2. https://www.ncbi.nlm.nih.gov/pubmed/8879974
  3. https://www.ncbi.nlm.nih.gov/pubmed/17473847?dopt=Abstract
  4. https://www.ncbi.nlm.nih.gov/pubmed/24112034
  5. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5972004/
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