title: Structural analysis and evaluation of the 11beta-hydroxysteroid dehydrogenase type 2 (11beta-HSD2) gene in human essential hypertension.
abstract: 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.
authors.affiliation: INSERM U358, Hôpital Saint-Louis, Paris, France.
authors.forename: E
authors.initials: E
authors.lastname: Brand
authors.forename: N
authors.initials: N
authors.lastname: Kato
authors.forename: N
authors.initials: N
authors.lastname: Chatelain
authors.forename: Z S
authors.initials: ZS
authors.lastname: Krozowski
authors.forename: X
authors.initials: X
authors.lastname: Jeunemaitre
authors.forename: P
authors.initials: P
authors.lastname: Corvol
authors.forename: P F
authors.initials: PF
authors.lastname: Plouin
authors.forename: F
authors.initials: F
authors.lastname: Cambien
authors.forename: L
authors.initials: L
authors.lastname: Pascoe
authors.forename: F
authors.initials: F
authors.lastname: Soubrier
mesh_terms: 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
chemical_list: D006913:Hydroxysteroid Dehydrogenases; D042842:11-beta-Hydroxysteroid Dehydrogenases