High blood pressure due to AGTR1 gene variants

Blood pressure isn’t 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. The CDC estimates that about 1/3 of US adults have high blood pressure – and that it contributes to more than 410,000 deaths each in the US in a year. [ref] That is a lot…

High blood pressure has several contributing factors, and genetics is one of them.  There are quite a few genes that influence blood pressure, but I’m only going to focus on the angiotensin I receptors here.

High blood pressure (hypertension):

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

Systolic (top number):
120-139mmHg ‘high normal’; over 140mmHg is considered high or hypertension

Diastolic (bottom number):
80-89 mmHg ‘high normal’ [ref]; 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.

For some interesting reading on the topic of high blood pressure and heart disease, I recommend Dr. Malcolm Kendrick’s blog series on what causes heart disease.

Angiotensin II – a vasoconstrictor:

Angiotensin is a hormone that is part of 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 that 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:

AGTR1 gene:  Angiotensin II receptor type-1

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

  • A/A: normal 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]

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]
  • 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 above risk):

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

  • T/T: normal
  • C/T: increased risk of fatty liver disease in people
  • C/C:  almost 2-fold increased risk of fatty liver disease [ref], in people with cardiovascular disease[ref]

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

  • T/T: decreased risk of kidney cancer [ref]
  • C/T: normal risk of kidney cancer
  • C/C: normal risk of kidney cancer

 


Lifehacks:

High-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).

Natural angiotensin-receptor blockers include:[ref]

*Note that you don’t want to go overboard with high doses of supplemental potassium at one time. That said, there are many studies pointing to increased potassium in the diet being very helpful for hypertension. [ref]  Here is a complete list of potassium-containing foods. 

Also, 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.

 

*Amazon affiliate links are not an endorsement of a specific brand, rather for you to check out available supplements and decide on the best options for yourself.



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2 Comments on “High blood pressure due to AGTR1 gene variants

  1. wow – there must be some other genes relevant to blood pressure

    I am C/C on rs5186
    but I have very low blood pressure – so low that it causes issues sometimes

    • Hi Natalie –
      Yes – there are lots of other genetic factors for blood pressure. Plus diet and exercise are important as well – perhaps you are in great shape and exercise regularly :-)
      Thanks for reading,
      Debbie

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