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.

DESIGN:

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: Gareth G Lavery, Claire L McTernan, Stephen C Bain, Tahseen A Chowdhury, Martin Hewison, Paul M Stewart
• Journal: European journal of endocrinology (Eur J Endocrinol) Vol. 146 Issue 4 Pg. 553-8 (Apr 2002) ISSN: 0804-4643 [Print] England
• PMID: 11916625 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Dextrans
• hypertonic saline-dextran solution
• Sodium Chloride
• Hydroxysteroid Dehydrogenases
• 11-beta-Hydroxysteroid Dehydrogenase Type 2
• HSD11B2 protein, human

Topics

• 11-beta-Hydroxysteroid Dehydrogenase Type 2
• Adult
• Alleles
• Cohort Studies
• Dextrans
• Diabetes Mellitus, Type 1 (genetics)
• Diabetic Nephropathies (genetics)
• Female
• Gene Frequency
• Humans
• Hydroxysteroid Dehydrogenases (genetics)
• Introns (genetics)
• Male
• Microsatellite Repeats
• Middle Aged
• Reference Values
• Sodium Chloride