title: HSD11B2 CA-repeat and sodium balance.
abstract: Type 2 11β-hydroxysteroid dehydrogenase encoded by the HSD11B2 gene converts cortisol to inactive cortisone and thus protects the mineralocorticoid receptor from cortisol exposure. Impaired activity of this enzyme leads to mineralocorticoid excess, suggesting HSD11B2 as a candidate locus for patients at risk of developing low renin or salt-sensitive essential hypertension. In the present study, we searched for frequent polymorphisms in 155 Japanese subjects but detected none in the proximal promoter or coding regions of HSD11B2. Following this result, we genotyped a highly polymorphic CA-repeat polymorphism within the first intron in 848 normotensive and 430 hypertensive Japanese patients, and we then analyzed its association with disease and clinical parameters. We confirmed 12 alleles (12, 15-25 CA repeats) in the population and found no significant difference in the distribution of the allele length between normotensive and hypertensive patients. In 174 normal subjects without medication, urinary cortisol excretion was higher in subjects with more CA repeats in the shorter allele, but the ratio of urinary cortisone to cortisol, a reliable marker of renal HSD11B2 activity, did not differ. However, longer CA-repeat length was positively correlated with 24-h urinary sodium excretion, fractional sodium excretion and potassium clearance, and this observation was confirmed when the longer CA-repeat length was dichotomized. Thus, HSD11B2 CA-repeat genotype is not associated with hypertension itself, but with renal sodium excretion, probably through salt intake/appetite.
authors: Division of Diabetes, Endocrinology and Metabolism, Kawasaki Medical School, Kurashiki, Okayama, Japan. mune@med.kawasaki-m.ac.jp
authors: Tomoatsu
authors: T
authors: Mune
authors: Hiroyuki
authors: H
authors: Morita
authors: Nobuki
authors: N
authors: Takada
authors: Yoritsuna
authors: Y
authors: Yamamoto
authors: Yukinori
authors: Y
authors: Isomura
authors: Tetsuya
authors: T
authors: Suwa
authors: Jun
authors: J
authors: Takeda
authors: Perrin C
authors: PC
authors: White
authors: Kohei
authors: K
authors: Kaku
mesh_terms: D043209:11-beta-Hydroxysteroid Dehydrogenase Type 2 / Q000235:genetics*; D000328:Adult; D000368:Aged; D018900:Dinucleotide Repeats; D005838:Genotype; D006801:Humans; D006854:Hydrocortisone / Q000652:urine; D007668:Kidney / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D012964:Sodium / Q000378:metabolism*
chemical_list: D012964:Sodium; D043209:11-beta-Hydroxysteroid Dehydrogenase Type 2; C468387:HSD11B2 protein, human; D006854:Hydrocortisone