HUMAN HYPERTENSION CAUSED BY MUTATIONS IN THE KIDNEY ISOZYME OF 11-BETA-HYDROXYSTEROID DEHYDROGENASE

The syndrome of apparent mineralocorticoid excess (AME) is an inherite d form of human hypertension thought to result from a deficiency of 11 beta-hydroxysteroid dehydrogenase (11 beta HSD). This enzyme normally converts cortisol to inactive cortisone and is postulated to thus con fer specificity for aldosterone upon the mineralocorticoid receptor. W e have analysed the gene encoding the kidney isozyme of 11 beta HSD an d found mutations on both alleles in nine of 11 AME patients (eight of nine kindreds). These mutations markedly affect enzymatic activity. T hey thus permit cortisol to occupy the renal mineralocorticoid recepto r and thereby cause sodium retention and hypertension.