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]
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][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
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Check your genetic data for rs1799998 (23andMe v5; AncestryDNA):
- A/A: typical
- A/G: slightly increased heart disease risk[ref]
- G/G: increased relative risk of hypertension in many different population groups (but not all)[ref][ref][ref][ref]; increased relative risk of stroke[ref][ref]; increased risk of a-fib[ref]; higher relative risk of pre-eclampsia[ref] possibly a better response to angiotensin II receptor blocker drugs[ref][ref]
Members: Your genotype for rs1799998 is —.
Rare mutations in the CYP11B2 gene are linked to aldosterone synthase deficiency.
Check your genetic data for rs61757294 (AncestryDNA):
- G/G: rare mutation for aldosterone synthase deficiency[ref]
- A/G: carrier of a rare mutation for aldosterone synthase deficiency
- A/A: typical
Members: Your genotype for rs61757294 is —.
Check your genetic data for rs104894072 (23andMe v5; AncestryDNA):
- G/G: rare mutation for aldosterone synthase deficiency[ref]
- T/G: carrier of a rare mutation for aldosterone synthase deficiency
- T/T: typical
Members: Your genotype for rs104894072 is —.
Check your genetic data for rs28931609 (23andMe v4, v5):
- G/G: typical
- A/G: carrier of a rare mutation for aldosterone synthase deficiency
- A/A: rare mutation for aldosterone synthase deficiency[ref]
Members: Your genotype for rs28931609 is —.
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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.
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References:
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—. “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, https://doi.org/10.1159/000338498.
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“PharmGKB.” PharmGKB, https://www.pharmgkb.org/clinicalAnnotation/1183614600. Accessed 20 Sept. 2021.
“—.” PharmGKB, https://www.pharmgkb.org/clinicalAnnotation/1183614600. Accessed 20 Sept. 2021.
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Rs61757294 RefSNP Report – DbSNP – NCBI. https://www.ncbi.nlm.nih.gov/snp/rs61757294#clinical_significance. Accessed 20 Sept. 2021.
Rs104894072 RefSNP Report – DbSNP – NCBI. https://www.ncbi.nlm.nih.gov/snp/rs104894072?horizontal_tab=true#clinical_significance. Accessed 20 Sept. 2021.
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