Join Here   |   Log In

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]

CYP11B2 Genotype Report

Members: Log in to see your data below.
Not a member? Join here.
Why is this section is now only for members? Here’s why…

Member Content:

Not a member?

Join Here


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:

Member Content:

Not a member?

Join Here

Related Articles and Topics:

Heart Health Topic Summary
Utilize our Heart Health Topic Summary Reports with your 23andMe or AncestryDNA genetic data to see which articles may be most relevant to you. These summaries are attempting to distill the complex information down into just a few words. Please see the linked articles for details and complete references.

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.

LDL Cholesterol Genes
Heart disease is the leading cause of death in the US and around the world, and high LDL-cholesterol levels have been linked in many studies to increased heart disease. Learn how your genes impact LDL levels.

BMAL1’s impact on the “Big 3”: heart disease, cancer, and diabetes
A core circadian rhythm gene, BMAL1, influences heart disease risk, diabetes, and cancer. Check your genes and learn how to mitigate the risk.


Antonov, E. V., et al. “Aldosterone and Stress-Dependent Arterial Hypertension.” Bulletin of Experimental Biology and Medicine, vol. 152, no. 2, Dec. 2011, pp. 188–91. PubMed,
Azimi-Nezhad, Mohsen, et al. “Association of CYP11B2 Gene Polymorphism with Preeclampsia in North East of Iran (Khorasan Province).” Gene, vol. 733, Apr. 2020, p. 144358. PubMed,
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,
“Figure: Regulating Blood Pressure: The Renin-Angiotensin-Aldosterone System.” Merck Manuals Consumer Version, Accessed 20 Sept. 2021.
Gideon, Angelina, et al. “Kinetics and Interrelations of the Renin Aldosterone Response to Acute Psychosocial Stress: A Neglected Stress System.” The Journal of Clinical Endocrinology and Metabolism, vol. 105, no. 3, Mar. 2020, p. dgz190. PubMed,
Gong, Hongtao, et al. “Association of Polymorphisms of CYP11B2 Gene -344C/T and ACE Gene I/D with Antihypertensive Response to Angiotensin Receptor Blockers in Chinese with Hypertension.” Journal of Genetics, vol. 98, Mar. 2019, p. 1.
Gorini, Stefania, et al. “Mineralocorticoid Receptor and Aldosterone-Related Biomarkers of End-Organ Damage in Cardiometabolic Disease.” Biomolecules, vol. 8, no. 3, Sept. 2018, p. 96. PubMed Central,
Jia, En-Zhi, et al. “Renin-Angiotensin-Aldosterone System Gene Polymorphisms and Coronary Artery Disease: Detection of Gene-Gene and Gene-Environment Interactions.” Cellular Physiology and Biochemistry: International Journal of Experimental Cellular Physiology, Biochemistry, and Pharmacology, vol. 29, no. 3–4, 2012, pp. 443–52. PubMed,
—. “Renin-Angiotensin-Aldosterone System Gene Polymorphisms and Coronary Artery Disease: Detection of Gene-Gene and Gene-Environment Interactions.” Cellular Physiology and Biochemistry: International Journal of Experimental Cellular Physiology, Biochemistry, and Pharmacology, vol. 29, no. 3–4, 2012, pp. 443–52. PubMed,
Kurland, Lisa, et al. “Aldosterone Synthase (CYP11B2) -344 C/T Polymorphism Is Related to Antihypertensive Response: Result from the Swedish Irbesartan Left Ventricular Hypertrophy Investigation versus Atenolol (SILVHIA) Trial.” American Journal of Hypertension, vol. 15, no. 5, May 2002, pp. 389–93. PubMed,
Li, Xinghui, et al. “CYP11B2 Gene Polymorphism and Essential Hypertension among Tibetan, Dongxiang and Han Populations from Northwest of China.” Clinical and Experimental Hypertension (New York, N.Y.: 1993), vol. 38, no. 4, 2016, pp. 375–80. PubMed,
Li, Yan-yan, et al. “CYP11B2 T-344C Gene Polymorphism and Atrial Fibrillation: A Meta-Analysis of 2,758 Subjects.” PloS One, vol. 7, no. 11, 2012, p. e50910. PubMed,
Mulatero, Paolo, et al. “CYP11B2 -344T/C Gene Polymorphism and Blood Pressure in Patients with Acromegaly.” The Journal of Clinical Endocrinology and Metabolism, vol. 91, no. 12, Dec. 2006, pp. 5008–12. PubMed,
Munshi, Anjana, et al. “Association of the −344C/T Aldosterone Synthase (CYP11B2) Gene Variant with Hypertension and Stroke.” Journal of the Neurological Sciences, vol. 296, no. 1, Sept. 2010, pp. 34–38. ScienceDirect,
Peter, M., et al. “Hereditary Defect in Biosynthesis of Aldosterone: Aldosterone Synthase Deficiency 1964-1997.” The Journal of Clinical Endocrinology and Metabolism, vol. 82, no. 11, Nov. 1997, pp. 3525–28. PubMed,
“PharmGKB.” PharmGKB, Accessed 20 Sept. 2021.
“—.” PharmGKB, Accessed 20 Sept. 2021.
“Primary Aldosteronism – Symptoms and Causes.” Mayo Clinic, Accessed 20 Sept. 2021.
Rs28931609 RefSNP Report – DbSNP – NCBI. Accessed 20 Sept. 2021.
Rs61757294 RefSNP Report – DbSNP – NCBI. Accessed 20 Sept. 2021.
Rs104894072 RefSNP Report – DbSNP – NCBI. Accessed 20 Sept. 2021.
Schoppen, Stefanie, et al. “Sodium-Bicarbonated Mineral Water Decreases Aldosterone Levels without Affecting Urinary Excretion of Bone Minerals.” International Journal of Food Sciences and Nutrition, vol. 59, no. 4, June 2008, pp. 347–55. PubMed,
Toxqui, Laura, and M. Pilar Vaquero. “Aldosterone Changes after Consumption of a Sodium-Bicarbonated Mineral Water in Humans. A Four-Way Randomized Controlled Trial.” Journal of Physiology and Biochemistry, vol. 72, no. 4, Dec. 2016, pp. 635–41. PubMed,
Wang, Lijuan, et al. “Association between Single-Nucleotide Polymorphisms in Six Hypertensive Candidate Genes and Hypertension among Northern Han Chinese Individuals.” Hypertension Research: Official Journal of the Japanese Society of Hypertension, vol. 37, no. 12, Dec. 2014, pp. 1068–74. PubMed,
Wils, Julien, et al. “The Neuropeptide Substance P Regulates Aldosterone Secretion in Human Adrenals.” Nature Communications, vol. 11, no. 1, May 2020, p. 2673. PubMed,
Young, William F. “Primary Aldosteronism: Renaissance of a Syndrome.” Clinical Endocrinology, vol. 66, no. 5, May 2007, pp. 607–18. PubMed,

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.