Titre du document / Document title

Association studies between the HSD11B2 gene (encoding human 11 β-hydroxysteroid dehydrogenase type 2), type 1 diabetes mellitus and diabetic nephropathy

Auteur(s) / Author(s)

LAVERY Gareth G. ⁽¹⁾ ; MCTERNAN Claire L. ⁽¹⁾ ; BAIN Stephen C. ⁽²⁾ ; CHOWDHURY Tahseen A. ⁽³⁾ ; HEWISON Martin ⁽¹⁾ ; STEWART Paul M. ⁽¹⁾ ;

Affiliation(s) du ou des auteurs / Author(s) Affiliation(s)

⁽¹⁾ Division of Medical Sciences, University of Birmingham, Queen Elizabeth Hospital, Edgbaston, Birmingham B15 2TH, ROYAUME-UNI
⁽²⁾ Birmingham Heartlands Hospital, Bordesley Green East, Birmingham B9 5SS, ROYAUME-UNI
⁽³⁾ Jeffrey Kelson Diabetic Centre, Central Middlesex Hospital, London NW10 7NS, ROYAUME-UNI

Résumé / Abstract

Objective: Mutations in the HSD11B2 gene (encoding human 1 1β-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 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD2) activity and may, in part. explain the enhanced salt sensitivity observed in patients with type 1 diabetes.

Revue / Journal Title

European journal of endocrinology   ISSN 0804-4643 

Source / Source

2002, vol. 146, n^o4, pp. 553-558 (35 ref.)

Langue / Language

Anglais

Editeur / Publisher

Portland Press, Colchester, ROYAUME-UNI  (1994) (Revue)

Mots-clés anglais / English Keywords

Cardiovascular disease ; Urinary system disease ; Endocrinopathy ; Autoimmune disease ; Immunopathology ; Kidney disease ; Enzyme ; Oxidoreductases ; Locus ; Phenotype ; Sensitivity ; Salt ; Mineralocorticoid ; Dehydrogenase ; Human ; Gene ; Renal function ; Intron ; Allele ; Mutation ; Hypertension ; Hydrocortisone ; Nephropathy ; Non insulin dependent diabetes ; Insulin dependent diabetes ;

Mots-clés français / French Keywords

Appareil circulatoire pathologie ; Appareil urinaire pathologie ; Endocrinopathie ; Maladie autoimmune ; Immunopathologie ; Rein pathologie ; Enzyme ; Oxidoreductases ; Locus ; Phénotype ; Sensibilité ; Sel ; Minéralocorticoïde ; Dehydrogenase ; Homme ; Gène ; Fonction rénale ; Intron ; Allèle ; Mutation ; Hypertension artérielle ; Hydrocortisone ; Néphropathie ; Diabète non insulinodépendant ; Diabète insulinodépendant ;

Mots-clés espagnols / Spanish Keywords

Aparato circulatorio patología ; Aparato urinario patología ; Endocrinopatía ; Enfermedad autoinmune ; Inmunopatología ; Riñón patología ; Enzima ; Oxidoreductases ; Locus ; Fenotipo ; Sensibilidad ; Sal ; Mineralocorticoide ; Dehydrogenase ; Hombre ; Gen ; Función renal ; Intrón ; Alelo ; Mutación ; Hipertensión arterial ; Hidrocortisona ; Nefropatía ; Diabetes no insulinodependiente ; Diabetes insulinodependiente ;

Localisation / Location

INIST-CNRS, Cote INIST : 5321, 35400010096239.0150