[Genetics and arterial hypertension: monogenic forms].
Hypertension is a complex, multifactorial disease; genetic factors represent one third to half of the inter-individual variability of blood pressure values. The study of genes involved in rare forms of monogenic hypertension led to the identification of pivotal pathophysiological pathways of kidney sodium and water reabsorption that can influence blood pressure values when changed. Glucocorticoid-Remediable Aldosteronism (GRA) is characterised by normal to high aldosterone levels, despite plasma renin activity suppression, and by the fact that these alterations are corrected by exogenous glucocorticoid administration. Apparent Mineralocorticoid Excess (AME) is due to a mutation of the gene encoding the renal isoform of 11 â HSD enzyme; the non-conversion of cortisol to cortisone result in increasing cortisol levels that activate the mineralocorticoid receptor. Early onset hypertension exacerbating during pregnancy is caused by a mutation leading to a conformational change in the mineralocorticoid receptor. Therefore, substances that are normally inactive at this level, such as progesterone, become potent agonists of the mutated receptor. Liddle's syndrome (or type I pseudo-hyperaldosteronism (PHA1), is characterised by a constitutive activation of the epithelial sodium channels in the distal tubule, causing an increase in sodium and chloride reabsorption. Gordon syndrome (Type II pseudo-hyperaldosteronism, PHA2) differs from the other forms because of the presence, in addition to hypertension, of hyperkaliemia and hyperchloremic acidosis that can be normalized with thiazide diuretics. Finally, a large pedigree of Turkish origin has been described: these patients are affected by an uncertain form of monogenic hypertension associated with brachydactyly.
Fortunato
M
M
Cattedra e Scuola di Specializzazione in Nefrologia, Università degli Studi di Milano, Sesto San Giovanni (MI)-Italy.
Caruso
S
S
Del Vecchio
L
L
Procaccio
M
M
Tedoldi
S
S
Vigano'
S
S
Cusi
D
D
D005938:Glucocorticoids / Q000627:therapeutic use; D006706:Homeostasis; D006801:Humans; D006929:Hyperaldosteronism / Q000188:drug therapy / Q000235:genetics; D006973:Hypertension / Q000235:genetics*; D009154:Mutation; D012964:Sodium / Q000378:metabolism
D005938:Glucocorticoids; D012964:Sodium