A NEW POLYMORPHIC RESTRICTION SITE IN THE HUMAN 11-BETA-HYDROXYSTEROID DEHYDROGENASE TYPE-2 GENE

The 11 beta-hydroxysteroid dehydrogenase type II enzyme (11 beta HSD2) inactivates glucocorticoids in the kidney and thus prevents glucocort icoids from occupying the non-selective mineralocorticoid receptor in epithelial tissues. Mutations in the HSD11B2 gene have been found to c ause the syndrome of apparent mineralocorticoid excess, a rare autosom al recessive disease characterized by severe hypertension. Thus, this locus could also be an ideal candidate involved in the etiology of pri mary hypertension. We identified a polymorphism in exon 3 characterize d by a GAG to GAA transition at codon 178, with the loss of an Alu I r estriction site and analysed it in an association study using end-stag e renal disease patients, diabetic or essential hypertensive patients and control subjects. Two-hundred and eighty nine subjects and patient s were analysed; the genotype was determined by amplification of genom ic DNA and subsequent digestion with Alu I restriction enzyme. The pre valence of the Alu I allele was 8.6% in healthy control subjects (n=11 6). This prevalence was lower (chi(2) P=0.035 vs, controls) than the 1 8.0% 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%, respective ly. There was no correlation between blood pressure and the marker in non-ESRD subjects. These data indicate the presence of a polymorphic m arker in exon 3 of the HSD11B2 gene; this marker is associated with en d-stage renal disease but not with essential hypertension in humans.