CYP11B2

The CYP11B2 gene provides instructions for making an enzyme called aldosterone synthase. 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. These enzymes are involved in many processes in the body.

Aldosterone synthase helps produce a hormone called aldosterone. Aldosterone helps control blood pressure by maintaining proper salt and fluid levels in the body. The aldosterone synthase enzyme is involved in a series of three chemical reactions that produce aldosterone: the conversion of 11-deoxycorticosterone to corticosterone, the conversion of corticosterone to 18-hydroxycorticosterone, and the conversion of 18-hydroxycorticosterone to aldosterone.

familial hyperaldosteronism - increased risk from variations of the CYP11B2 gene

The genetic change responsible for familial hyperaldosteronism type I fuses the section of the CYP11B2 gene that contains the instructions for making aldosterone synthase to a section of a nearby gene called CYP11B1. The added part of the CYP11B1 gene contains a section called a promoter region, which normally starts the production of the 11-beta-hydroxylase enzyme from the CYP11B1 gene. As part of the fused gene, the CYP11B1 gene's promoter region instead starts the production of aldosterone synthase from the CYP11B2 gene.

The activity of the CYP11B1 gene's promoter region is triggered by a hormone called adrenocorticotropic hormone (ACTH). As a result of the fused gene, aldosterone synthase activity is abnormally responsive to ACTH levels, resulting in excessive amounts of aldosterone being produced. The excessive aldosterone production leads to the high blood pressure (hypertension) associated with familial hyperaldosteronism type I.

other disorders - caused by mutations in the CYP11B2 gene

Mutations in the CYP11B2 gene also cause two forms of corticosterone methyloxidase deficiency: type I, which is found in the Amish community, and type II, which has been identified in the Iranian Jewish population. CYP11B2 gene mutations associated with corticosterone methyloxidase deficiency interfere with the step of aldosterone synthesis in which corticosterone is converted to 18-hydroxycorticosterone. Individuals with corticosterone methyloxidase deficiency produce little or no aldosterone and lose large amounts of sodium in their urine, which can be life-threatening.