title: Association studies between the HSD11B2 gene (encoding human 11beta-hydroxysteroid dehydrogenase type 2), type 1 diabetes mellitus and diabetic nephropathy.
abstract: OBJECTIVE
  Mutations in the HSD11B2 gene (encoding human 11beta-hydroxysteroid dehydrogenase type 2) explain the syndrome of apparent mineralocorticoid excess where cortisol acts as a mineralocorticoid. A microsatellite marker within the HSD11B2 gene associates with salt sensitivity and hypertension--phenotypes characterising diabetic nephropathy. Here, we evaluate the HSD11B2 gene as a susceptibility locus for diabetic nephropathy.
  
  
  METHODS
  150 patients with type 1 diabetes and nephropathy (DN), 145 patients with type 1 diabetes with a long duration of non-nephropathy (LDNN) and 151 normal controls were studied.
  
  
  METHODS
  We determined allele frequencies for the (CA)n repeat marker within intron I of the HSD11B2 gene. Duration of type 1 diabetes, diabetic status and renal function were recorded.
  
  
  RESULTS
  11 alleles (138-158) for the marker were observed. Allele 152 was significantly increased in controls compared with LDNN (70.5% vs 57.6%, P(c)<0.05 where P(c) is the P value corrected for multiple comparisons) but no difference was observed between DN and LDNN subjects. Allele 154 was significantly increased in the LDNN compared with the DN subjects (15.9% vs 7.0%, P(c)<0.01) but no difference was observed between DN and controls. A greater proportion of subjects carried at least 1 allele <152 in DN compared with control subjects (47.3% vs 28.5%, P(c)<0.01), but no difference was observed in LDNN compared with control and DN subjects.
  
  
  CONCLUSIONS
  Weak associations are reported between the HSD11B2 gene, type 1 diabetes mellitus and nephropathy. The increased frequency of HSD11B2 short alleles in the diabetic groups may reflect reduced renal 11beta-hydroxysteroid dehydrogenase type 2 (11beta-HSD2) activity and may, in part, explain the enhanced salt sensitivity observed in patients with type 1 diabetes.
authors.affiliation: Division of Medical Sciences, University of Birmingham, Queen Elizabeth Hospital, Edgbaston, Birmingham B15 2TH, UK.
authors.forename: Gareth G
authors.initials: GG
authors.lastname: Lavery
authors.forename: Claire L
authors.initials: CL
authors.lastname: McTernan
authors.forename: Stephen C
authors.initials: SC
authors.lastname: Bain
authors.forename: Tahseen A
authors.initials: TA
authors.lastname: Chowdhury
authors.forename: Martin
authors.initials: M
authors.lastname: Hewison
authors.forename: Paul M
authors.initials: PM
authors.lastname: Stewart
mesh_terms: D043209:11-beta-Hydroxysteroid Dehydrogenase Type 2; D000328:Adult; D000483:Alleles; D015331:Cohort Studies; D003911:Dextrans; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics*; D003928:Diabetic Nephropathies / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D006801:Humans; D006913:Hydroxysteroid Dehydrogenases / Q000235:genetics*; D007438:Introns / Q000235:genetics; D008297:Male; D018895:Microsatellite Repeats; D008875:Middle Aged; D012016:Reference Values; D012965:Sodium Chloride
chemical_list: D003911:Dextrans; C104375:hypertonic saline-dextran solution; D012965:Sodium Chloride; D006913:Hydroxysteroid Dehydrogenases; D043209:11-beta-Hydroxysteroid Dehydrogenase Type 2; C468387:HSD11B2 protein, human