heart & blood vessels

nutrition

SLC4A5

Does This Gene Affect Salt Sensitivity and Blood Pressure? (SLC4A5)

Written by Mathew Eng, PharmD on March 20th, 2020

The SLC4A5 gene helps regulate the body’s sodium and pH levels. Certain genetic variants of SLC4A5 may disrupt this balance, potentially leading to salt sensitivity. Find out how this gene works, what salt sensitivity is, and who may be affected.

The SLC4A5 Gene

The SLC4A5 gene is responsible for producing a protein called electrogenic sodium-bicarbonate cotransporter 4, also known as NBCe2 [R].

This NBCe2 protein acts as a transporter that helps balance the body’s pH and sodium (salt) levels [R].

There’s some evidence that certain variants of SLC4A5 may alter the function of the NBC32 protein, leading to salt sensitivity [R, R].

What Is Salt Sensitivity?

The body needs a certain amount of salt (also known as sodium) to function properly. Salt plays essential roles in regulating blood pressure, blood volume, water balance, and pH balance [R].

However, consuming too much salt can lead to several health issues, such as increasing the risk of developing high blood pressure [R].

Interestingly, researchers are finding that dietary salt can affect individuals differently.

People who are salt sensitive will see larger increases in blood pressure in response to dietary salt compared to people who are less sensitive [R].

In contrast, individuals who are salt-insensitive or salt-resistant see little change in blood pressure in response to dietary salt, even when consuming large amounts [R].

Several factors can affect salt sensitivity, but many studies suggest that genetics may play a significant role [R].

How Does SLC4A5 Affect Salt Sensitivity?

Research suggests that certain variants of the SLC4A5 gene may be linked to salt sensitivity and high blood pressure [R, R].

However, it’s not completely clear exactly how these particular genetic variants lead to salt sensitivity.

Some researchers theorize that these variants may increase the amount of salt that the kidneys reabsorb from the urine. This means that more salt is retained in the body, which can increase blood pressure [R, R].

Who Is Affected?

One study of 185 Caucasian individuals found that two SNPs in the SLC4A5 gene may be associated with salt sensitivity — rs7571842 and rs10177833 [R].

More specifically, the ‘A’ allele in both these SNPs was linked to significantly higher increases in blood pressure in response to salt intake compared to other alleles [R].

Another study of 20 Caucasian adults also found that the ‘A’ allele in rs7571842 is associated with salt sensitivity [R].

In addition, this second study suggests that those carrying the ‘A’ allele in rs10177833 tend to consume greater amounts of salt and that salt taste perception is linked to salt sensitivity [R].

According to a third study of almost 200 West African women, the ‘C’ allele of rs8179526 is linked to significantly higher systolic blood pressures [R].

The ‘A’ allele of rs7571842 and rs10177833 is linked to salt sensitivity, while the ‘C’ allele of rs8179526 is associated with high blood pressure.

Your SLC4A5 Results for Salt Sensitivity

You can see your genotypes for SLC4A5 in the table below. However, keep in mind that these associations are based on studies from certain ethnic populations — so you should interpret your results with caution if you are not descended from one of these specific groups!

SNP Table

variant	genotype	frequency	risk allele
rs7571842
rs10177833
rs8179526

SNP Summary and Table

Primary SNPs:

SLC4A5 rs7571842

‘G’ = Not associated with salt sensitivity
‘A’ = Associated with salt sensitivity
This association has only been found in Caucasian populations
About 21% of people worldwide have the ‘AA’ genotype (highest risk)

SLC4A5 rs10177833

‘C’ = Not associated with salt sensitivity
‘A’ = Associated with salt sensitivity and higher salt intake
This association has only been found in Caucasian populations
About 28% of people worldwide have the ‘AA’ genotype (highest risk)

SLC4A5 rs8179526

‘T’ = Not associated with blood pressure
‘C’ = Associated with higher systolic blood pressures
This association has only been found in West African women
About 41% of people worldwide have the ‘CC’ genotype (highest risk)

Population Frequencies

In the SLC4A5 gene the frequency of alleles can vary greatly depending on ethnicity.

For example, the ‘AA’ genotype of rs7571842 (which is associated with the highest risk of salt sensitivity) is found in about 12% of East Asians, 29% of Europeans, and 44% of South Asians.

The ‘AA’ genotype of rs10177833 follows a very similar trend — the frequency is lowest in East Asians, higher in Europeans, and highest in South Asians.

For rs8179526, the ‘CC’ genotype is present in about 49% of East Asians, 28% of Europeans, and 63% of South Asians.

Recommendations

Lifestyle

Exercise Regularly

A number of studies show that regular physical activity is a great way to improve salt sensitivity.

For example, one study of nearly 2,000 Chinese individuals found that participants who had little to no daily exercise had blood pressure elevations that were almost double the values seen in those that get regular physical activity [R].

Another study of 31 older adults with high blood pressure found that, after 6 months of aerobic exercise training, the number of salt-resistant individuals increased by about 26% [R].

How does exercise help?

Researchers believe that physical activity may improve salt sensitivity through several mechanisms, including reduced insulin resistance, improved blood vessel function, and inhibition of the sympathetic nervous system [R].

In addition, when you sweat as a result of exercise, you can excrete a decent amount of salt. This is why people in marathons consume salt tablets or salty foods.

Besides beneficial effects on salt sensitivity, research shows that regular exercise has significant benefits to heart health and overall longevity [R, R].

Diet

Controlling Salt In The Diet

Unsurprisingly, reducing the amount of salt in the diet is one of the best ways to improve salt sensitivity and control blood pressure [R].

Individuals who are salt sensitive need to pay close attention to the salt content of the foods that they eat.

Some foods that are typically guilty of having high amounts of salt include [R]:

Deli meats
Canned soups
Frozen meals
Pizza
Breads and sandwiches

How much salt should be in the diet?

Generally speaking, adults should consume no more than 2,300 mg of sodium each day [R].

Ideally, this limit should be closer to 1,500 mg of sodium each day as studies show that this lower limit has even more health benefits [R].

However, if your blood pressure is relatively lower (under 110/70), then you may want to consume more salt than these recommendations [R].

One common diet approach for those with high blood pressure is the DASH diet, which is short for Dietary Approaches to Stop Hypertension.

The DASH diet was developed to help lower blood pressure without the need for medications. It emphasizes the consumption of vegetables, fruits, and low-fat dairy foods [R].

The DASH diet is also an important component of the MIND diet, which is designed to support brain health and general wellness [R].

Mathew Eng

PharmD

Mathew received his PharmD from the University of Hawaii and an undergraduate degree in Biology from the University of Washington.

Mathew is a licensed pharmacist with clinical experience in oncology, infectious disease, and diabetes management. He has a passion for personalized patient care and believes that education is essential to living a healthy life. His goal is to motivate individuals to find ways to manage their chronic conditions.

Disclaimer

The information on this website has not been evaluated by the Food & Drug Administration or any other official medical body. This information is presented for educational purposes only, and may not be used to diagnose or treat any illness or disease.

Also keep in mind that the “Risk Score” presented in this post is based only on a select number of SNPs, and therefore only represents a small portion of your total risk as an individual. Furthermore, these analyses are based primarily on associational studies, which do not necessarily imply causation. Finally, many other (non-genetic) factors can also play a significant role in the development of a disease or health condition — therefore, carrying any of the risk-associated genotypes discussed in this post does not necessarily mean you are at increased risk of developing a major health condition.

Always consult your doctor before acting on any information or recommendations discussed in this post — especially if you are pregnant, nursing, taking medication, or have been officially diagnosed with a medical condition.

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Content

The SLC4A5 Gene How Does SLC4A5 Affect Salt Sensitivity? Your SLC4A5 Results for Salt Sensitivity

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