ACE Gene: The Key To A Fit And Healthy Lifestyle!

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:

High blood pressure
Heart failure
Diabetes
Chronic kidney disease
Coronary artery disease
Scleroderma
Migraines

Common examples of ACE inhibitors are:

Enalapril
Captopril
Ramipril
Lisinopril

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:

Cough
Red, itchy skin or rash
Dizziness and lightheadedness
Metallic taste
Decreased ability to taste
Severe vomiting and diarrhea
Swelling of the neck, tongue, and face
Hyperkalaemia or excessive potassium in the blood
Kidney failure

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.

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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:

Stroke
Vision loss
Heart attack
Heart failure
Kidney disease

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:

Environmental factors such as lack of exercise, stress
Increase in blood plasma volume
Hormonal activity
Some medications
Smoking
Familial history of high blood pressure
Diabetes
Chronic kidney conditions
Hyperthyroidism
Hyperparathyroidism
Pregnancy
Obesity
Pheochromocytoma
Sleep apnea

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

Sweating
Anxiety
Blushing and flushing
Sleep problems
Frequent headaches
Nosebleeds

What are the four stages of hypertension?

Stage	Severity	Blood pressure range (mm Hg)
I	Prehypertension	120/80 to 139/89
II	Mild Hypertension	140/90 to 159/99
III	Moderate Hypertension	160/100 to 179/109
IV	Severe Hypertension	180/110 or higher

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.

Count your calories and keep track of what you eat.
- Reducing caloric intake and eating adequate portions of high fiber foods can help you reduce weight, lose fat, and reduce cholesterol levels in the body.
- All these together can bring down your blood pressure levels.
Avoid sodium.
- Increased sodium in your diet results in increased blood pressure levels.
- Therefore, reduce your sodium intake and increase the absorption of other minerals, such as potassium and magnesium.
Increase your intake of fresh fruits and vegetables.
Consume probiotics.
Avoid high carbohydrate foods.
Avoid excessive fatty foods, especially those who are rich in saturated fats.

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:

7-8 servings of grains
4-5 servings each of fruits and vegetables
2-3 servings of low-fat or fat-free dairy products
1-2 servings of lean meat or fish
4-5 servings of nuts and seeds per week
2-3 servings of oil or fat
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.

SNP	Genotype	Implications
rs2106809	AA	Small decrease in the diastolic blood pressure when treated with captopril
	AG	Small decrease in diastolic blood pressure when treated with captopril
	GG	Higher decrease in diastolic blood pressure when treated with captopril as compared to women with the AA or AG genotype.

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