title: A new polymorphic restriction site in the human 11 beta-hydroxysteroid dehydrogenase type 2 gene.
abstract: The 11 beta-hydroxysteroid dehydrogenase type II enzyme (11 beta HSD2) inactivates glucocorticoids in the kidney and thus prevents glucocorticoids from occupying the non-selective mineralocorticoid receptor in epithelial tissues. Mutations in the HSD11B2 gene have been found to cause the syndrome of apparent mineralocorticoid excess, a rare autosomal recessive disease characterized by severe hypertension. Thus, this locus could also be an ideal candidate involved in the etiology of primary hypertension. We identified a polymorphism in exon 3 characterized by a GAG to GAA transition at codon 178, with the loss of an Alu I restriction site and analysed it in an association study using end-stage renal disease patients, diabetic or essential hypertensive patients and control subjects. Two-hundred and eighty nine subjects and patients were analysed; the genotype was determined by amplification of genomic DNA and subsequent digestion with Alu I restriction enzyme. The prevalence of the Alu I allele was 8.6% in healthy control subjects (n = 116). This prevalence was lower (chi 2 P = 0.035 vs. controls) than the 18.0% in a group of renal transplant patients (n = 61). The corresponding values for patients with diabetes mellitus (n = 25), hypertension (n = 41) and patients on dialysis (n = 46) were 4.0%, 4.8% and 4.3%, respectively. There was no correlation between blood pressure and the marker in non-ESRD subjects. These data indicate the presence of a polymorphic marker in exon 3 of the HSD11B2 gene; this marker is associated with end-stage renal disease but not with essential hypertension in humans.
authors.affiliation: Department of Medicine, University Hospital of Berne, Switzerland.
authors.forename: Z
authors.initials: Z
authors.lastname: Smolenicka
authors.forename: E
authors.initials: E
authors.lastname: Bach
authors.forename: A
authors.initials: A
authors.lastname: Schaer
authors.forename: S
authors.initials: S
authors.lastname: Liechti-Gallati
authors.forename: B M
authors.initials: BM
authors.lastname: Frey
authors.forename: F J
authors.initials: FJ
authors.lastname: Frey
authors.forename: P
authors.initials: P
authors.lastname: Ferrari
mesh_terms: D042842:11-beta-Hydroxysteroid Dehydrogenases; D000328:Adult; D000368:Aged; D001483:Base Sequence; D003062:Codon; D015252:Deoxyribonucleases, Type II Site-Specific / Q000378:metabolism*; D003920:Diabetes Mellitus / Q000201:enzymology; D005091:Exons; D005260:Female; D006801:Humans; D006913:Hydroxysteroid Dehydrogenases / Q000235:genetics*; D006973:Hypertension / Q000201:enzymology; D007527:Isoenzymes / Q000235:genetics*; D007676:Kidney Failure, Chronic / Q000201:enzymology; D016030:Kidney Transplantation; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length
chemical_list: D003062:Codon; D007527:Isoenzymes; D006913:Hydroxysteroid Dehydrogenases; D042842:11-beta-Hydroxysteroid Dehydrogenases; C024669:endodeoxyribonuclease AluI; D015252:Deoxyribonucleases, Type II Site-Specific