High blood pressure due to AGTR1 gene variants

Blood pressure may not be something that you think much about – unless your doctor is harping about it being high or low.  The CDC statistics, though, make a pretty compelling argument that a lot of us should be thinking about blood pressure. It is estimated that ~ 1/3 of US adults have high blood pressure, which contributes to more than 410,000 deaths each in the US in a year. [refTrusted Source: Peer Reviewed Paper]

Genetics combines with diet and lifestyle factors to cause high blood pressure.  Additionally, there are quite a few genes that influence blood pressure, but this article only focuses on one (impactful) gene, AGTR1 (angiotensin I receptors).

High blood pressure:

Researchers, doctors, public health officials, etc all seem to have different ways of defining high blood pressure (hypertension). In general, the following blood pressure ranges are what is used in most studies for adults.

Systolic (top number):

  • less than 120 is good
  • 120-139mmHg ‘high normal’
  • over 140mmHg is considered high or hypertension

Diastolic (bottom number):[refTrusted Source: Peer Reviewed Paper]

  • less than 80 is good
  • 80-89 mmHg ‘high normal’
  • over 90 mmHg is considered high

The Mayo Clinic explains that high blood pressure can be due to the amount of blood pumped and the amount of resistance – or constriction – in the arteries.[ref]Your body’s blood pressure is a tightly regulated system that depends on a lot of factors.

 

Angiotensin II – a vasoconstrictor:

Angiotensin is a hormone in the renin-angiotensin-aldosterone system (RAAS) of blood pressure regulation. To increase blood pressure, angiotensin II causes the blood vessels to constrict, thus upping the pressure.

Angiotensin I is a precursor hormone that is converted into angiotensin II by the ACE enzyme (angiotensin-converting enzyme). Stopping the conversion of angiotensin I into II by blocking the ACE enzyme decreases blood pressure.  ACE inhibitors are a commonly used type of blood pressure medication. (See article on ACE gene variants)

For angiotensin II to constrict blood vessels (and increase blood pressure) it must bind to its receptor. The AGTR1 gene codes for the angiotensin II receptor type-1.  Common genetic variants increase the expression of the angiotensin II receptor 1 (AGTR1) gene — thus causing blood pressure to increase when there is abundant angiotensin II.


Genetic variants:

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AGTR1 gene:  Angiotensin II receptor type-1:

Check your genetic data for rs5186 A1166C (23andMe v4, v5; AncestryDNA):

  • A/A: typical variant; decreased risk of chronic kidney disease [refTrusted Source: Peer Reviewed Paper]
  • A/C: increased angiotensin II receptors;  increased risk of higher blood pressure[refTrusted Source: Peer Reviewed Paper]
  • C/C: increased angiotensin II receptors; a 2 to 7-fold increased risk of high blood pressure[refTrusted Source: Peer Reviewed Paper][refTrusted Source: Peer Reviewed Paper][refTrusted Source: Peer Reviewed Paper], increased risk of fatty liver, insulin resistance[refTrusted Source: Peer Reviewed Paper]

Members: Your genotype for rs5186 is .

It is important to note that the increased risk of high blood pressure seems to be the greatest in Caucasian populations.  Some studies of other population groups find a smaller increase in the risk of high blood pressure[refTrusted Source: Peer Reviewed Paper] or even no statistical risk. [refTrusted Source: Peer Reviewed Paper]

Other studies on this variant show that the rs5186 A/C or C/C genotype is associated with:

  • an increased risk of psoriasis [refTrusted Source: Peer Reviewed Paper]
  • left ventricular dysfunction (3-fold increased risk) [refTrusted Source: Peer Reviewed Paper]
  • an increased relative risk of endometrial cancer [refTrusted Source: Peer Reviewed Paper]
  • an increased risk of metabolic syndrome in males [refTrusted Source: Peer Reviewed Paper]
  • in pregnancy, an increased risk of hypertensive disorders (pre-eclampsia) [refTrusted Source: Peer Reviewed Paper][refTrusted Source: Peer Reviewed Paper]

Other AGTR1 genetic variants (less impactful but perhaps adding to above risk):

Check your genetic data for rs3772622 (23andMe v4, v5; AncestryDNA):

  • T/T: typical
  • C/T: increased risk of fatty liver disease in people
  • C/C:  almost 2-fold increased risk of fatty liver disease [refTrusted Source: Peer Reviewed Paper], in people with cardiovascular disease[refTrusted Source: Peer Reviewed Paper]

Members: Your genotype for rs3772622 is .

Check your genetic data for rs1492078 (23andMe v4; AncestryDNA):

  • T/T: decreased risk of kidney cancer [refTrusted Source: Peer Reviewed Paper]
  • C/T: typical risk of kidney cancer
  • C/C: typical risk of kidney cancer

Members: Your genotype for rs1492078 is .

 


Lifehacks:

Suggestions to lower blood pressure:

Low-fat diet?
Some studies suggest that a high-fat diet, in part, increases the rs5186 impact on blood pressure. [refTrusted Source: Peer Reviewed Paper] If you have high blood pressure and carry the risk allele for rs5186, try experimenting with a lower-fat diet to see if it decreases your blood pressure.

Sodium intake:
You may be assuming that salt consumption would interact with this genetic variant… (I did!)  But I could only find one research study that looked at salt sensitivity and the AGTR1 gene. It showed no interaction. [refTrusted Source: Peer Reviewed Paper]

Blood pressure meds:
The commonly prescribed blood pressure medications losartan and valsartan act on the AGTR1 receptor, as do other angiotensin receptor blockers (ARBs).

Natural angiotensin-receptor blockers include:[refTrusted Source: Peer Reviewed Paper]

  • Potassium – foods rich in potassium include bananas, potatoes with skin, dark leafy greens; supplemental potassium is also available in 99mg doses. Be careful, you don’t want to go overboard with high doses of supplemental potassium at one time since it can throw off your electrolyte balance. Many studies point to increased potassium in the diet being very helpful for hypertension.[ref]  Here is a complete list of potassium-containing foods. 
  • Resveratrol –  available as a supplement
  • Taurine – shellfish is high in taurine, and it is available as a supplement
  • Vitamin B6 – found in dairy, salmon, eggs, liver and as a supplement
  • CoQ10 – abundant in beef heart (which is actually quite tasty if marinated and grilled) and available in supplement form
  • Garlic – available at your grocery store

Furthermore, if you are on blood pressure medication, check with your doctor before adding in any of the natural supplements that lower blood pressure. The interaction could cause your blood pressure to go too low.

More to read

For some interesting reading on the topic of high blood pressure and heart disease, check out  Dr. Malcolm Kendrick’s blog series on what causes heart disease. He has a bit of a contrarian view of the role of cholesterol in heart disease, and his writing is informative and thought-provoking.


Related Genes and Topics:

Diet and Blood Pressure
Research shows that people with the ACE deletion genotype are likely to have an increase in blood pressure on a high-fat diet. Find out how a high-fat diet interacts with your genes.

PCSK9 Variants
There are several important variants in the PCSK9 gene. Some variants cause lower LDL-cholesterol and decrease the risk of heart disease by 2-fold. Other variants increase LDL-c and increase the risk of heart disease.



Author Information:   Debbie Moon
Debbie Moon is the founder of Genetic Lifehacks. She holds a Master of Science in Biological Sciences from Clemson University. Debbie is a science communicator who is passionate about explaining evidence-based health information. Her goal with Genetic Lifehacks is to bridge the gap between scientific research and the lay person's ability to utilize that information. To contact Debbie, visit the contact page.