2.5.5. *CYP11B2*

The *CYP11B2* gene encodes for a cytochrome P450 protein, a monooxygenase which catalyzes the synthesis of cholesterol, steroids, and other lipids in the inner mitochondrial membrane; also known as aldosterone synthase, this enzyme has an 18-hydroxylase activity to synthesize aldosterone and 18-oxocortisol as well as steroid 11 beta-hydroxylase activity and is the rate limiting step in aldosterone production [107].

The largest study to date from 3 African countries examined several variants of genes implicated in low renin-resistant hypertension in Africans with suppressed renin and increased aldosterone. Six candidate genes were sequenced, including *CYP11B2*, *SCNN1B*, *NEDD4L*, *GRK4*, Uromodulin (*UMOD*), and Natriuretic Peptide A (*NPPA*) based on the renin-aldosterone status [105]. Fourteen nonsynonymous variants of *CYP11B2* were found, with 3 previously described and associated with alterations in aldosterone synthase production (R87G, V386A, and G435S) [105]. Further studies are required to ascertain these findings.

Apparent mineralocorticoid excess (AME) refers to a rare autosomal recessive disorder leading to low renin hypertension due to alterations in *HSD11B2* (16q22.1), which encodes for the corticosteroid 11-beta-dehydrogenase. This is a microsomal enzyme complex responsible for the interconversion of cortisol and cortisone in the kidneys, thus preventing the activation of the mineralocorticoid receptor by glucocorticoids. Variants in this gene have been associated with essential hypertension [108–110], likely through decreased cortisol inactivation to cortisone which is seen with aging, and biochemically confirmed as elevated urinary tetrahydrocortisol (THF, A-ring-reduced cortisol metabolite) + alloTHF to tetrahydrocortisone (THE, cortisol metabolite) [(THF+alloTHF)/THE] [111]. One study demonstrated an association between microsatellite markers close to the *HSD11B2* gene and hypertension in African Americans that also suffered from end-stage renal disease likely due to hypertension [53,112]. Further studies are required to confirm this association with the increased predisposition of African Americans to low-renin, salt-sensitive hypertension.
