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.[ref]

Genetics combine with diet and lifestyle factors to cause high blood pressure.  While there are quite a few genes that influence blood pressure, this quick article only focuses in on one (impactful) gene, AGTR1 (angiotensin II receptors). Members will see their genotype report below, plus additional solutions in the Lifehacks section. Join today 

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 are 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):[ref]

  • 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), which regulates blood pressure. 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, logically called the angiotensin II receptor type-1.

The AGTR1 gene codes for the angiotensin II receptor type-1.

Common genetic variants in AGTR1 increase the expression of the angiotensin II receptor 1 — thus causing blood pressure to increase when there is abundant angiotensin II in your system.

Angiotensin receptor blockers (ARBs), a class of blood pressure medication, act on AGTR1. Common medications here include losartan and valsartan. 

More than just high blood pressure…

In addition to blood vessels, the angiotensin II receptor is found in the kidneys and lungs. AGTR1 affects the way your kidneys respond to sodium and affects the changes that occur in kidney disease due to diabetes.[ref]

Cancer needs lots of nutrients via blood vessels for growth, and AGTR1 genetic variants are also tied into cancer risk. Additionally, endometriosis, which is an overgrowth of endometrial tissues, is linked to AGTR1 variants.[ref][ref]


AGTR1 Genotype Report

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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[ref]
  • A/C: increased angiotensin II receptors; increased risk of higher blood pressure[ref]
  • C/C: increased angiotensin II receptors; a 2 to 7-fold increased risk of high blood pressure[ref][ref][ref], increased risk of fatty liver, insulin resistance[ref]

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[ref] or even no statistical risk.[ref]

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

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

Other AGTR1 genetic variants (less impactful but perhaps adding to the 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, especially in people with cardiovascular disease[ref][ref]

Members: Your genotype for rs3772622 is .

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

  • T/T: decreased risk of kidney cancer[ref] (good!)
  • 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. [ref] 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.[ref]

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

The rest of this article is for Genetic Lifehacks members only.  Consider joining today to see the rest of this article.

Natural angiotensin-receptor blockers include:[ref]

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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.


About the Author:
Debbie Moon is the founder of Genetic Lifehacks. Fascinated by the connections between genes, diet, and health, her goal is to help you understand how to apply genetics to your diet and lifestyle decisions. Debbie has a BS in engineering and also an MSc in biological sciences from Clemson University. Debbie combines an engineering mindset with a biological systems approach to help you understand how genetic differences impact your optimal health.