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A New Polymorphic Restriction Site in the Human 11ß-Hydroxysteroid Dehydrogenase Type 2 Gene

Division of Nephrology and Hypertension, Department of Medicine (Z.S., E.B., A.S., B.M.F., F.J.F., P.F.) and Unit of Human Molecular Genetics (S.L-G.), University Hospital of Berne, Inselspital, 3010 Berne, Switzerland

Address correspondence and requests for reprints to: P. Ferrari, M.D., Division of Nephrology and Hypertension, Freiburgstrasse 3, Inselspital, 3010 Berne, Switzerland. This work was supported by grants from the Cloëtta Foundation and the Swiss National Foundation for Scientific Research (Nr 3200-049835 and Nr 40-44802.95).

Abstract

ABTRACT

The 11ß-hydroxysteroid dehydrogenase type II enzyme (11ßHSD2) inactivates glucocorticoids in the kidney and thus prevents glucocorticoids from occupying the non-selective mineralocorticoid receptor in epithelial tissues. Mutants 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 analyzed it in an association study using end-stage renal disease patients, diabetic or essential hypertensive patients and control subjects. Two-hundred eighty nine subjects and patients were analyzed; 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 (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.

Received February 24, 1998.

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This Article Abstract Full Text (PDF) Submit a related Letter to the Editor Purchase Article View Shopping Cart Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Smolenicka, Z. Articles by Ferrari, P Search for Related Content PubMed PubMed Citation Articles by Smolenicka, Z. Articles by Ferrari, P