ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Endocrine Abstracts (2008) 16 P26

Glucocorticoid receptor gene polymorphisms and bone mineral density in hpa axis disorders

Giorgio Arnaldi, Gloria Appolloni, Paola Romagni, Marina Cardinaletti, Laura Trementino, Barbara Polenta, Carolina Concettoni & Marco Boscaro


Division of Endocrinology, Marche Region, Ancona, Italy.


Glucocorticoid receptor (GR) gene polymorphisms have been associated with interindividual variations in glucocorticoid sensitivity in healthy individuals.

Aim: Aim of this study was to investigate whether there was an association with sensitivity to glucocorticoids and bone mineral density in HPA axis disorders.

Methods: We analyzed 3 polymorphisms of the GR gene (Bcl1, N363S, ER22/23EK) in 185 subjects: 52 patients with Cushing’s Syndrome (CS), 32 patients with adrenal incidentaloma (AI), 101 healthy subjects (C). The patients were compared by anthropometric and clinical indices and bone mineral density (BMD) at spine and femoral neck levels. Genotype frequencies were assessed for each polymorphism.

Results: The groups did not differ for age, sex, and BMI. Lumbar BMD was significantly lower in CS and AI compared to C, while there were no differences in femoral neck BMD. Lumbar and femoral neck z-score was significantly lower in CS compared to both AI and C. For N363S and ER22/23EK polymorphisms the allelic frequency was 1.89% and 0.81% respectively, so no associations with hormonal and bone parameters was evaluated. For BclI polymorphism, allelic frequencies were 28.1% in CS, 27.8% in AI, 41.2% in C. Heterozygous C/G was more prevalent (P<0.03) in CS and AI (n=16/32; P<0.03) than in C. After dexamethasone suppression test, CG carriers had lower cortisol levels than C/C carriers in CS, while no significant differences were found in AI and CG. Only in the lumbar spine a tendency towards lower BMD in CG carriers was found in AI, while no differences were found in femoral neck BMD and z-score. Lumbar and femoral neck BMD and z-score did not differ in C/G carriers with CS. In conclusion, we found an association between Bcl I polymorphism and GC sensitivity in subjects with Cushing’s syndrome suggesting that this polymorphism might be associated with lower bone mineral density.

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