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

Endocrine Abstracts (2008) 16 P676

Glucocorticoid receptor gene polymorphisms in patients with Cushing's disease and adrenal Cushing's syndrome

Ágnes Szappanos1, Attila Patócs2, Judit Toke1, Márta Sereg1, László Futo3, Zoltán Kende4, Ibolya Varga2, Edit Gláz1, Károly Rácz1 & Miklós Tóth1

1Department of Medicine, Semmelweis University, Budapest, Hungary; 2Molecular Medicine Research Group, Hungarian Academy of Sciences and 2nd Department of Medicine, Semmelweis University, Budapest, Hungary; 31st Department of Medicine, Markhot Ferenc Hospital, Eger, Hungary; 4Semmelweis University, Budapest, Hungary.

Introduction: The hypothalamic–pituitary–adrenal axis setpoint and the glucocorticoid sensitivity in various tissues are at least partly genetically determined. The glucocorticoid receptor (GR) gene polymorphisms may have an impact on the development and/or the variability of clinical manifestations of endogenous hypercortisolism, however their role has not been investigated in patients with endogenous hypercortisolism.

Methods: We investigated the potential involvement of the BclI, N363S, ER22/23EK and A3669G polymorphisms of the GR gene in 58 patients with endogenous hypercortisolism (35 patients with Cushing’s disease (CD) and 23 with adrenal Cushing’s syndrome (ACS). The BclI and the N363S variants were detected by allele-specific polymerase chain reaction, the ER22/23EK by PCR-RFLP method and the A3669G variant by Taqman allelic discrimination assay. Genotype distributions were compared to those measured in 129 healthy control subjects. All patients underwent a detailed clinical and hormonal evaluation, which included measurements of plasma cortisol (at 0800/2400 and after low dose dexamethasone suppression test) and plasma ACTH concentration.

Results: No statistically significant differences were found in the allelic frequencies of the GR gene polymorphisms between patients and controls. The frequency of the BclI polymorphism was underrepresented in patients with ACS compared to healthy subjects but the differences between these groups were not statistically significant (P=0.066). None of the studied GR gene polymorphisms were associated with concentrations of plasma cortisol and/or plasma ACTH.

Conclusion: Our findings show that the four investigated genetic variants of the GR gene probably do not involved in the pathophysiology of CD and ACS.

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