Genotype-phenotype correlations of mutations and polymorphisms in HSD11B2,the gene encoding the kidney isozyme of 11 beta-hydroxysteroid dehydrogenase

Mutations in the HSD11B2 gene encoding the kidney (11-HSD2) isozyme of 11 b eta -hydroxysteroid dehydrogenase cause the syndrome of apparent mineraloco rticoid excess, a form of salt-sensitive hypertension. Enzymatic activities of mutant enzymes measured in cultured cells are correlated with several p arameters of clinical severity including urinary steroid product:precursor ratios, age at diagnosis, birth weight and potassium levels, but not with b lood pressure. In normals or in subjects with essential hypertension, sensi tivity of blood pressure to salt loading is correlated with activity of ren al 11-HSD2, as measured by an increase in the ratio of urinary free cortiso l/urinary free cortisone UFF/UFE), and also correlated with length of a CA repeat polymorphism in the first intron of HSD 11B2. A functional explanati on for these associations remains to be elucidated.