CYP11B2 gene
The CYP11B2 gene provides instructions for making the enzyme aldosterone synthase, which is critical for blood pressure regulation and fluid balance.
Normal Function
The CYP11B2 gene provides instructions for making an enzyme called aldosterone synthase (previously known as corticosterone methyloxidase). This enzyme is found in the adrenal glands, which are located on top of the kidneys. Aldosterone synthase is a member of the cytochrome P450 family of enzymes, which are involved in the formation and breakdown of various molecules within cells.
Aldosterone synthase helps produce a hormone called aldosterone. Aldosterone helps control blood pressure by maintaining proper salt and fluid levels in the body. The enzyme is involved in a series of three chemical reactions that produce aldosterone from precursor molecules: the conversion of 11-deoxycorticosterone to corticosterone, the conversion of corticosterone to 18-hydroxycorticosterone, and the conversion of 18-hydroxycorticosterone to aldosterone.
Health Conditions Related to Genetic Changes
Corticosterone methyloxidase deficiency
At least 30 CYP11B2 gene mutations that cause corticosterone methyloxidase deficiency (also known as aldosterone synthase deficiency) have been identified. These mutations lead to insufficient production of aldosterone, which impairs the kidneys' ability to reabsorb salt (sodium chloride) into the blood and release potassium in the urine. The resulting imbalance of ions leads to:
- Nausea
- Vomiting
- Dehydration
- Low blood pressure
- Extreme tiredness (fatigue)
- Muscle weakness
Familial hyperaldosteronism
A genetic change affecting the CYP11B2 gene causes familial hyperaldosteronism type I, a disorder that leads to high blood pressure (hypertension). This change fuses the section of the CYP11B2 gene containing instructions for making aldosterone synthase to a section of a nearby gene called CYP11B1.
The added part of the CYP11B1 gene contains a promoter region, which normally helps start the production of an enzyme called 11-beta-hydroxylase. In the fusion gene, the hormone adrenocorticotropic hormone (ACTH)—which normally triggers 11-beta-hydroxylase—abnormally triggers the production of aldosterone synthase. High levels of aldosterone synthase result in excessive aldosterone production, leading to hypertension.
Other disorders
Normal variations (polymorphisms) of the CYP11B2 gene have been associated with an increased risk of cardiovascular problems, including hypertension, stroke caused by a lack of blood flow to the brain (ischemic stroke), and a heart rhythm abnormality called atrial fibrillation in people with heart failure.