Analysis of the 11beta-hydroxysteroid dehydrogenase type 2 gene (HSD11B2) in human essential hypertension.
BACKGROUND
The HSD11B2 gene, encoding the kidney isoenzyme 11beta-hydroxysteroid dehydrogenase, is a candidate for essential hypertension. We previously showed that the frequency of shorter alleles of a CA repeat polymorphism in the first intron of 11beta-HSD2 gene was significantly higher among salt-sensitive than salt-resistant individuals with hypertension. The aim of the study was to analyze the HSD11B2 gene to assess whether some of its variants might be involved in hypertension.


METHODS
Exons 2, 3, 4, and 5 were screened by polymerase chain reaction-single-strand conformation polymorphism analysis in 292 hypertensive patients and 163 control subjects. The samples with variant electrophoretic patterns at single-strand conformation polymorphism were re-analyzed using an automated DNA sequencer. A case-control study was then performed by comparing genotype frequencies in hypertensive and normotensive subjects.


RESULTS
Analysis of the HSD11B2 showed that in hypertensive patients there is a higher prevalence of two associated polymorphisms, Thr156/Thr(C468A) in exon 2 (ex2) and Glu178/Glu(G534A) in exon 3 (ex3), than in normotensive subjects (9% v 2.4%). This association did not correlate with salt sensitivity. C468A alone correlates significantly with hypertension (9%) and was identified only in 3% of control subjects (P < .05), whereas G534A was identified also in about 7% of normotensive subjects. The urinary free cortisol/urinary free cortisone ratio (UFF/UFE) was significantly higher in hypertensive patients compared with control subjects (P < .01).


CONCLUSIONS
Two different polymorphisms of the HSD11B2 gene were observed. The association of both polymorphisms was significantly higher in hypertensive subjects than in control subjects. Its role should be further investigated, but it could be related to other mutations in the promoter region of HSD11B2 or to the modulation of 11beta-HSD2 mRNA processing in hypertensive subjects.
Mariniello
Barbara
B
Division of Endocrinology, Department of Internal Medicine, Università Politecnica delle Marche, Umberto I Hospital, Ancona, Italy.
Ronconi
Vanessa
V
Sardu
Cipriana
C
Pagliericcio
Antonella
A
Galletti
Ferruccio
F
Strazzullo
Pasquale
P
Palermo
Mario
M
Boscaro
Marco
M
Stewart
Paul M
PM
Mantero
Franco
F
Giacchetti
Gilberta
G
D043209:11-beta-Hydroxysteroid Dehydrogenase Type 2 / Q000235:genetics*; D001483:Base Sequence; D001794:Blood Pressure / Q000502:physiology; D016022:Case-Control Studies; D004247:DNA / Q000737:chemistry / Q000235:genetics; D004252:DNA Mutational Analysis; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D006973:Hypertension / Q000201:enzymology / Q000235:genetics* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D017354:Point Mutation; D018807:Polymorphism, Single-Stranded Conformational
D004247:DNA; D043209:11-beta-Hydroxysteroid Dehydrogenase Type 2; C468387:HSD11B2 protein, human