Because hypertension in Black people tends to be of the low-renin, salt sensitive type, we genotyped independent sets of hypertensives of Afro-American (59 kindreds) and Afro-Caribbean (66 kindreds) origin using a highly polymorphic (heterozygosity index 0.84) CA repeat polymorphism in the first intron of HSD11B2.
The decreased activity of 11beta-HSD2 increases the intracellular availability of cortisol, which might be relevant for the pathogenesis of hypertension and preeclampsia.
11beta-HSD2 protects the mineralocorticoid receptor from cortisol excess; mutations in the HSD11B2 gene explain an inherited form of hypertension, the syndrome of 'apparent mineralocorticoid excess', in which 'Cushing's disease of the kidney' results in cortisol-mediated mineralocorticoid excess.
Mutations in the gene encoding 11beta-HSD2 (HSD11B2) account for an inherited form of hypertension, the syndrome of "Apparent Mineralocorticoid Excess" (AME) where cortisol induces hypertension and hypokalaemia.
AME represents a spectrum of mineralocorticoid hypertension with severity reflecting the underlying genetic defect in the 11beta-HSD2; although AME is a genetic disorder, several exogenous compounds can bring about the symptoms by inhibiting 11beta-HSD2 enzyme.
Impaired 11beta-HSD2 activity has been suggested in patients with hypertension as well as in patients with renal disease, where it may contribute to sodium retention, oedema and hypertension.
In AME, defective HSD11B2 enzyme activity results in overstimulation of the mineralocorticoid receptor (MR) by cortisol, causing sodium retention, hypokalemia, and salt-dependent hypertension.
Epidemiological data suggests that polymorphic variability in the HSD11B2 gene determines salt sensitivity in the general population, which is a key predisposing factor to adult onset hypertension in some patients.
Therefore, impaired 11beta-HSD2 protein stability rather than reduced gene expression or loss of catalytic activity seems to be responsible for the development of hypertension in some individuals with AME.
These findings indicate that variants of the HSD11B2 gene may contribute to the enhanced blood pressure response to salt and possibly to hypertension in humans.
To gain insight into potentially relevant miRNAs in vivo, we investigated 2 models with differential 11β-HSD2 activity linked with salt-sensitive hypertension.
Post-translational histone methylation at different histone 3 lysine residues was also observed to control the expression of genes related to AH as lysine-specific demethylase-1(LSD1), HSD11B2, and epithelial sodium channel subunit α (SCNN1A).
The isozyme 11beta-HSD2 is selectively expressed in mineralocorticoid target tissues and its activity is reduced in various disease states with abnormal sodium retention and hypertension, including the apparent mineralocorticoid excess.