Structural analysis and evaluation of the 11beta-hydroxysteroid dehydrogenase type 2 (11beta-HSD2) gene in human essential hypertension.
OBJECTIVE
Mutations of the 11beta-hydroxysteroid dehydrogenase type 2 (11beta-HSD2) gene cause the syndrome of apparent mineralocorticoid excess, a rare autosomal recessive form of hypertension. We therefore investigated the question of whether variants of the 11beta-HSD2 gene can contribute to genetic susceptibility to essential hypertension.


METHODS
We performed a linkage study in 162 French hypertensive sibships using the affected sib-pair method on 347 sibling pairs and a polymorphic microsatellite marker that we identified in a 30 kb cosmid clone containing the 11beta-HSD2 gene. The coding sequence, introns 2-4 and 350 bp of the 5'-flanking region of the 11beta-HSD2 gene were screened for polymorphisms by polymerase chain reaction/single-strand conformation polymorphism, and a single polymorphism, Glu178/Glu (G534A), was identified in exon 3, which did not change the encoded amino acid sequence. A case-control study was conducted on 370 hypertensive subjects with a positive family history of hypertension and 783 French subjects with hypertension with or without a family history of hypertension, compared with 313 normotensive control subjects, all of whom were analyzed for the newly identified bi-allelic polymorphism.


RESULTS
Statistical analyses using the affected sib-pair method did not show significant linkage between the 11beta-HSD2 microsatellite marker and hypertension. Furthermore, no positive association with hypertension was found with the Glu178/Glu (G534A) polymorphism.


CONCLUSIONS
Our data do not suggest that variants of the 11beta-HSD2 gene contribute substantially to essential hypertension in Caucasians.
Brand
E
E
INSERM U358, Hôpital Saint-Louis, Paris, France.
Kato
N
N
Chatelain
N
N
Krozowski
Z S
ZS
Jeunemaitre
X
X
Corvol
P
P
Plouin
P F
PF
Cambien
F
F
Pascoe
L
L
Soubrier
F
F
D042842:11-beta-Hydroxysteroid Dehydrogenases; D000483:Alleles; D001483:Base Sequence; D016022:Case-Control Studies; D003627:Data Interpretation, Statistical; D005192:Family Health; D005787:Gene Frequency; D005796:Genes / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D006913:Hydroxysteroid Dehydrogenases / Q000235:genetics*; D006973:Hypertension / Q000235:genetics*; D018895:Microsatellite Repeats; D008969:Molecular Sequence Data; D011110:Polymorphism, Genetic
D006913:Hydroxysteroid Dehydrogenases; D042842:11-beta-Hydroxysteroid Dehydrogenases