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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? 

StageSeverityBlood pressure range (mm Hg)
IPrehypertension120/80 to 139/89
IIMild Hypertension140/90 to 159/99
IIIModerate Hypertension160/100 to 179/109
IVSevere Hypertension180/110 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.

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.

SNPGenotypeImplications
rs2106809 AASmall decrease in the diastolic blood pressure when treated with captopril
AGSmall decrease in diastolic blood pressure when treated with captopril
GGHigher 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 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/

The hepatic lipase gene (LIPC) is associated with the synthesis of hepatic lipase enzyme (LIPC) which catalyzes the hydrolysis of fat. Hepatic lipase converts intermediate-density lipoprotein (IDL) to low-density lipoprotein (LDL).It is expressed in the liver and in the adrenal glands. Specific alleles of this gene are known to either increase or decrease hepatic lipase levels, and due to linkage disequilibrium, the levels of lipoprotein lipase, which is associated with variations in the plasma HDL levels.  People with the T variant of the gene are shown to be associated with higher baseline HDL levels.

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

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

Association with Weight Loss Upon Exercise:

People with the C variant of the gene were associated with reduction in weight, body fat and visceral fat.

Association with Plasma Lipoprotein Levels upon Exercising (atherogenic effects):

In a study investigating the effects of endurance training on plasma lipoprotein levels, people with the C variant of the gene have been found to be associated with exercise mediated reduction in VLDL and increase in HDL. The benefit of exercise was found to be more in men with CC genotype than women.

Association with Childhood Obesity:

In a meta-analysis study conducted on children, boys with the T allele had a higher BMI and higher risk of obesity. In another study, boys with the T variant of the gene were found to be associated with higher HDL level on high fat intake.

Association with Dietary Fat intake:

In a study conducted to determine gene-nutrient interactions, people with the T variant on a low fat diet (less than 30% of energy from fat) have been shown to be associated with higher HDL levels. In a study conducted to identify how Chinese, Malays and Asian Indians in Singapore were exposed to similar environment but where Asian Indians had three times the rates of myocardial infarction compared to Chinese, found that a complex interplay of environmental and genetic factors gave rise to these ethnic differences. A high fat diet was shown to be associated with higher serum triglyceride and lower HDL-cholesterol concentrations in people with the T variant while those with the C variant were shown to be associated with lower serum triglyceride and higher HDL cholesterol under the same dietary conditions. People with the T variant of the gene may have an impaired adaptation to a high fat diet, increasing the risk for cardiovascular disease.

Association with Insulin Sensitivity:

In a study conducted on the LIPC gene variant and insulin sensitivity, the baseline insulin sensitivity was found to be similar between the gene variants but, upon exercising, people with the C variant were shown to be associated with higher insulin sensitivity. In a similar study, men with the T variant were shown to be associated with an improvement in insulin sensitivity when MUFA and carbohydrate rich are consumed instead of SFA fat. There was no association with women with the T variant and between diet and insulin sensitivity among men and women with the C variant.

GenotypePhenotypeRecommendation
CC[Limitation] More likely to have lower baseline HDL [Advantage] More likely to have higher HDL level upon exercising [Advantage] More likely to have higher HDL on high fat diet [Advantage] More Likely to have improvement in insulin sensitivity upon exercising [Limitation] Less Likely to have improvement in insulin sensitivity when on MUFA and Carbohydrate rich dietLikely increase in HDL upon exercising Including exercise routines is beneficial to HDL levels and insulin sensitivity
CTSlightly improved insulin sensitivity upon exercisingLikely increase in HDL upon exercising Including exercise routines is beneficial to HDL levels and insulin sensitivity
TT[Advantage] More likely to have higher baseline HDL [Limitation] Less likely to have higher HDL level upon exercising [Limitation] More likely to have Lower HDL on high fat diet [Limitation] Less Likely to have improvement in insulin sensitivity upon exercising [Advantage] More Likely to have improvement in insulin sensitivity when on MUFA and Carbohydrate rich dietLikely increase in HDL level when on MUFA and Carbohydrate rich diet People with this gene variant would benefit from consuming low fat diet and carbohydrate rich diet


References
:

  1. https://www.ncbi.nlm.nih.gov/pubmed/12403660
  2. http://ajcn.nutrition.org/content/81/6/1429.full.pdf
  3. https://www.ncbi.nlm.nih.gov/pubmed/9114024
  4. https://www.ncbi.nlm.nih.gov/pubmed/23550552
  5. https://goo.gl/I8cAcl
  6. http://apjcn.nhri.org.tw/server/APJCN/14/s/72.pdf
  7. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3053582/

Nutrigenetics, fitness genetics, health genetics are all nascent but rapidly growing areas within human genetics. The information provided herein is based on preliminary scientific studies and it is to be read and understood in that context.”

I am your heart. I work really hard to keep you alive. Every minute I pump out 5 litres of oxygen rich blood to every cell in your body so you can think, move, speak, work and live. In return all I ask is that you keep me healthy. Not many people around the world do that. In fact approximately 17.3 million people die every year because heart disease. By 2020, it will be the leading cause of death around the world.

So let’s have a conversation. Heart to heart. Here are 7 natural ways you can prevent a heart attack.

 

1. Eat Healthy

Look towards healthy foods that help lower cholesterol. Eat vegetables and fish that have lots of good fats. Don’t eat as much red meat, choose lean meats instead. Eat a serving of nuts (walnuts, almonds etc.) every day. Drink less of carbonated beverages and drink natural fruit juices without added sugar. Get 4-5 servings of fresh vegetables. Feeling like having a snack? Skip the chips and salty foods and munch on some fresh carrots instead. Search and build your own book of healthy recipes for breakfast, lunch and dinner. Trust me, your heart will thank you for it.

2. Exercise

With more of us having less active jobs than ever before, a lack of exercise is a big risk factor for heart disease. On the bright side, it also means that exercising regularly in addition to eating healthy is one of the fastest ways to reduce your risk! Research shows that getting just 30 minutes of aerobic exercise five times a week can significantly reduce the risk of a heart attack. Can’t spare 30 minutes at a stretch? Sneak in three 10 minute sessions of brisk walking or exercise whenever you get a break.

3. Get adequate rest

We’re living in a 24X7 world. The computers and mobile devices that allow us to connect to the internet and each other whenever we want have also taken away proper sleep habits. We sacrifice sleep for work and for leisure without realizing the effect that it has on our body. Scientific studies have shown that people who get less than 6 hours of sleep a night have a higher chance of getting high blood pressure and high cholesterol both of which contribute to heart disease. So put down that phone, turn off the TV and get some sleep.

4. Quit smoking

Smoking can double the risk of you having a heart attack. Smoking damages the blood vessels and increases the risk of them being blocked leading to higher chances of a heart attack. Women who take birth control pills and smoke are particularly at a higher risk to develop heart disease. Even smoking for a brief period of time damages the heart. Nicotine in cigarettes or chewing tobacco reduces the oxygen supply to the heart and increases blood pressure. So if you smoke, make a healthy start and quit today.

5. Drink alcohol in strict moderation

If you drink alcohol, be sure to strictly control how much you drink. Drinking alcohol excessively has been shown to increase the risk for hypertension, obesity and heart disease. Alcohol intake above moderate levels also increases cholesterol levels leading to formation of plaques and blood vessel blockage.

6. Practice Yoga and Meditation

Among other benefits, yoga and meditation have been shown to significantly reduce stress and have positive effects on mind and body. Yoga comprises of physical exercises as well as training to control the breath. In combination with meditation, yoga can improves many physiological functions and be extremely effective as a preventive mechanism for heart attacks.

7. Know your numbers and your risk factors

Lastly, always be aware of your health status. According to Barry A Franklin PhD Director of Preventive Cardiology and Rehabilitation at William Beaumont Hospital in Michigan USA and an American Heart Association Volunteer “Regular cardiovascular screening is important because it helps you detect risk factors in their earliest stages”. See your physician regularly and get your cholesterol and triglyceride levels checked. Your genes can play a role in whether you are more likely to get heart disease. Know your family history and whether that puts you at an increased risk. In addition, an advanced program like Xcode’s Lifelong Wellness can analyze your genes for health risks and metabolic traits and give you a personalized nutrition and fitness plan that will put you on the on the path to a healthier lifestyle.

 

 

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