title: Genetics of the mineralocorticoid system in primary hypertension.
abstract: Abnormalities in steroid biosynthesis have been known for years to cause hypertension in some cases of congenital adrenal hyperplasia. In these patients hypertension usually accompanies a characteristic phenotype with abnormal sexual differentiation. Recently, the molecular basis of four forms of severe hypertension transmitted on an autosomal basis but without additional phenotypic features has been elucidated. All these conditions are characterized primarily by low plasma renin, normal or low serum potassium, and salt-sensitive hypertension, indicating an increased mineralocorticoid effect. These four disorders, the glucocorticoid remediable aldosteronism, the syndrome of apparent mineralocorticoid excess, the activating mutation of the mineralocorticoid receptor, and the Liddle syndrome are a consequence of either abnormal biosynthesis, metabolism, or action of steroid hormones, and are ultimately characterized by an overactivation of the epithelial sodium channel in distal renal tubules. Hyperactivity of this channel results in increased sodium reabsorption and volume expansion leading to an increase in blood pressure as well as potassium loss. With the advent of molecular biology in clinical practice, it has become evident that some genetic defect may present with a more discrete phenotype, with only moderate hypertension with or without hypokalemia as the sole feature. A search for genetic disorders of the mineralocorticoid axis should be an integral part of the diagnostic work-up, particularly in young adults with hypertension.
authors.affiliation: Division of Nephrology and Hypertension, Inselspital, University of Berne, Freiburgstrasse 10, 3010 Berne, Switzerland. paolo.ferrari@insel.ch
authors.forename: Paolo
authors.initials: P
authors.lastname: Ferrari
mesh_terms: D000311:Adrenal Glands / Q000502:physiology*; D000450:Aldosterone / Q000378:metabolism; D019405:Cytochrome P-450 CYP11B2 / Q000235:genetics*; D006801:Humans; D006854:Hydrocortisone / Q000378:metabolism; D006913:Hydroxysteroid Dehydrogenases / Q000235:genetics* / Q000378:metabolism; D006973:Hypertension / Q000235:genetics* / Q000378:metabolism; D008901:Mineralocorticoids / Q000235:genetics* / Q000378:metabolism; D009154:Mutation; D011188:Potassium / Q000097:blood; D018161:Receptors, Mineralocorticoid / Q000235:genetics; D012083:Renin / Q000097:blood; D015222:Sodium Channels / Q000235:genetics; D013252:Steroid 11-beta-Hydroxylase / Q000235:genetics*
chemical_list: D008901:Mineralocorticoids; D018161:Receptors, Mineralocorticoid; D015222:Sodium Channels; D000450:Aldosterone; D006913:Hydroxysteroid Dehydrogenases; D019405:Cytochrome P-450 CYP11B2; D013252:Steroid 11-beta-Hydroxylase; D012083:Renin; D011188:Potassium; D006854:Hydrocortisone