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Hypertension Risk Factor: CYP11B2 Variant

A regular heartbeat with blood just swooshing along, all day and night, is something that we take for granted. But the body’s regulation of blood pressure is truly complex and involves the heart, blood vessels, and kidneys. Aldosterone is a key player working to balance blood volume through kidney function.

Here we dig into one key enzyme, aldosterone synthase, which impacts blood pressure. Genetic variants in the aldosterone synthase gene increase the risk of high blood pressure and stroke.

What is aldosterone synthase?

CYP11B2 gene encodes aldosterone synthase, an enzyme involved in aldosterone biosynthesis.

First, what’s aldosterone? Aldosterone is a steroid hormone that regulates blood pressure and plasma sodium and potassium levels. It works on the kidneys to balance out electrolytes (Na+ and K+) as a way of influencing blood pressure and blood volume.

In the body, think of ‘water follows sodium’. We all know a meal high in salt can leave us feeling ‘puffy’, and the action here is of the same concept. Aldosterone influences the kidneys to retain sodium while also excreting potassium. This shift in the electrolyte balance that allows for sodium retention directly increases water retention…by water following sodium. This action allows for an increase in blood volume and pressure.[ref]

RAAS pathway. CC image from Merck Manuals

Aldosterone synthase is produced in the adrenal cortex and regulated by the RAAS pathway (renin-angiotensin-aldosterone system). As the limiting factor in aldosterone production, the aldosterone synthase enzyme is crucial for blood pressure regulation and electrolyte balance.

The aldosterone synthase enzyme catalyzes a reaction involving deoxycorticosterone in a multistep process to form aldosterone. Deoxycorticosterone is a steroid hormone produced by the adrenal glands, and it can also regulate potassium, similar to aldosterone. The key, though, is that deoxycorticosterone doesn’t usually decrease sodium levels much compared to potassium.

The precursor for deoxycorticosterone (and thus, aldosterone) is progesterone. The hormone progesterone is synthesized in the body from cholesterol.

What does high aldosterone cause?

High aldosterone is linked to:[ref][ref]

  • high blood pressure
  • stroke
  • headaches, fatigue (related to low potassium known as ‘hypokalemia’)
  • osteoporosis

Related Article: Osteoporosis Genes and Prevention Strategies

What does very low aldosterone cause?

Very low aldosterone levels are a serious problem. Lack of aldosterone, often found in Cushing’s disease, is linked to salt-wasting, growth retardation in children, and failure to thrive. Altered potassium levels and low blood pressure can also occur.[ref][ref]


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Medications for high blood pressure:

People with hypertension along with the G/G genotype for rs1799998, may respond well to certain blood pressure-reducing drugs ending in -sartans. The -sartan drugs are angiotensin II receptor blockers.[ref][ref] These agents block the action of angiotensin II thus causing vasodilation and increased sodium and water excretion. (Talk with your doctor, of course!)

Aldosterone synthase inhibitors are a new class of hypertensive drugs under development. Inhibiting CYP11B2 decreases aldosterone and subsequently increases deoxycorticosterone, thus changing sodium-potassium balance.[ref]

Another way that is being investigated for reducing aldosterone is to stop the stimulation of aldosterone in the adrenals. Substance P binds to a receptor to increase aldosterone synthase, and blocking that receptor with drugs (in clinical trials) reduced aldosterone.[ref] If Substance P sounds familiar, it is a neuropeptide released in pain, vomiting, and hot flashes. In the adrenal glands, substance P partly influences aldosterone stimulation.

Natural ways to reduce high blood pressure with CYP11B2:

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References:

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Azizi, Michel, et al. “Aldosterone Synthase Inhibition in Humans.” Nephrology, Dialysis, Transplantation: Official Publication of the European Dialysis and Transplant Association – European Renal Association, vol. 28, no. 1, Jan. 2013, pp. 36–43. PubMed, https://doi.org/10.1093/ndt/gfs388.
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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 from Colorado School of Mines and 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.