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Gene, Diet, Disease

ACE and Blood Pressure

Carriers of ACE gene D allele are more likely to develop hypertension with a high sodium and low potassium diet.  Over 50% of Africans and Caucasians and about 40% of Asians carry this allele.

Blood pressure is one of the parameters in monitoring a person’s health status. Hypertension (high blood pressure) is a strong risk factor for cardiovascular and renal diseases, including coronary heart disease, stroke, heart failure, and kidney failure. The blood pressure in human body is controlled by the renin–angiotensin system (RAS), which is modulated by genetic makeup and environmental factors (diet, life style, stress etc). Many blood pressure controlling drugs target the RAS system.

With regard to blood pressure regulation, the most common and well understood genetic variation is the angiotensin-converting enzyme (ACE) insertion/deletion (ACE I/D) polymorphism and the most influential dietary factor is sodium intake. Interactions between ACE I/D polymorphism, sodium intake and the RAS system dictates effectiveness of most blood pressure management regimens.

A key component of the RAS system, ACE acts as an enzyme that converts the inactive oligopeptides angiotensin I to the active form angiotensin II.  The later is a hormone that activates a series of reactions in human body, ultimately leading to blood pressure increase. The ACE I/D polymorphism is characterized by the presence (insertion, I) or absence (deletion, D) of a 287-bp Alu repeat sequence in an intron (non-coding segment) of the ACE gene.  The presence of the Alu repeat sequence affects the expression of the ACE gene, resulting in an increased ACE protein level, thus a more active RAS system in the D allele carriers and differential response to environmental factors such as dietary, exercise or medicines.

With regard to dietary interaction, the D allele carriers have a higher risk of blood pressure increase in response to high sodium intake. Therefore, low sodium diets are recommended for them.  In hypertensive, diabetic, overweight and obese, and other chronic cardiovascular or renal diseases populations, the harmful effects of high sodium on D allele carriers are aggravated. For D allele carriers in these populations, sodium restriction through low sodium and/or high potassium diet is especially important.

Most natural food does not contain significant amount of sodium.  Human dietary sodium comes mostly from added salt, either in the processed food or home cooking meals.  In modern Western life style, only a small amount of salt intake comes from the salt added at the table. Processed foods account for most of the added sodium. Therefore, the most effect way to reduce sodium intake is to choose low- or reduced-sodium, or no-salt-added versions of foods and condiments during shopping. Meanwhile, increase potassium intake also have the effect of sodium reduction since the absorption of sodium is operated by the Na+/K+ channel that transport Na+ and K+ at opposite directions.  A high sodium intake leads to potassium loss through urine. Vice versa, a high potassium intake leads to sodium excretion to the urine. The following table shows the most common potassium rich food sources.

Table 1. Common food sources that are rich in potassium (Derived from the DASH eating plan, USDA 2006).

Food Group Food Serving Size Potassium (mg)
Vegetables Potato 1 medium 926
Sweet potato 1 medium 540
Spinach, cooked 1/2 cup 290
Zucchini, cooked 1/2 cup 280
Tomato, fresh 1/2 cup 210
Fruits Banana 1 medium 420
Apricots 1/4 cup 380
Orange 1 medium 237
Cantaloupe chunks 1/2 cup 214
Apple 1 medium 150
Seeds Soybeans, cooked 1/2 cup 440
Lentils, cooked 1/2 cup 370
Kidney beans/split beans, cooked 1/2 cup 360
Almonds, roasted 1/3 cup 310
Walnuts, roasted 1/3 cup 190
Dairy and Meet Milk 1 cup 380
Yogurt 1 cup 370
Fish 3 oz 200-400
Pork, tenderloin 3 oz 370
Beef, chicken, turkey 3 oz 210

In responses to exercise and weight loss, D allele carriers response well to short sessions of strength and power oriented exercise and benefit more from weight loss whereas the I allele carriers are better suited for endurance exercise. Long term endurance exercise for D allele carriers actually increases their risk for an increased left ventricular mass, which is associated with increased cardiovascular mortality.

The ACE I/D polymorphism also associate with many chronic diseases.  The DD genotype is associated with higher risks for hypertension, atherosclerosis, coronary heart disease, stroke, diabetic nephropathy and migraine.  In many cases, the association is only significant in non-Caucasian populations. However, in ethnic background the association is enhanced by other chronic health conditions such as overweight and obese, diabetes and by environment stress such as high altitude, extreme exercise and certain medicines. Interestingly, the DD genotype is associated with a reduced risk for Alzheimer Disease, presumably due to the elevated ACE activity that may help degrade the amyloid beta peptide that causes plaques formation during the development of the disease.

The interactions of ACE I/D polymorphism and blood pressure control drugs have been investigated intensively for its implication in personalized medicine. In brief, differential responses do exist for certain medicines in certain ethnic population toward particular disease conditions.

It is not clear of the ACE I/D polymorphism which the major or ancestral allele is since both are present at high frequency in overall world population.  In general, the D allele is more frequent in African or Caucasians and the I allele is more frequent in Asian population (Table 2).

Table 2. Percentage of the ACE I/D polymorphism allele and genotype distribution across ethnicity and country. 

Ethnicity-Country Allele Genotype
African American-US 59 41 34 50 16
Asian-China 38 62 14 47 39
Asian-Japan 36 64 13 45 42
Caucasian-Australia 55 45 31 48 21
Caucasian-Finland 58 42 35 46 19
Caucasian-France 59 41 38 42 20
Caucasian-Germany 61 39 42 37 21
Caucasian-Italy 64 36 41 47 12
Caucasian-UK 51 49 36 46 18
Caucasian-US 56 44 30 52 18
Mexican-American 47 53 21 52 27

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