Introduction: The hypothalamicpituitaryadrenal 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 Cushings disease (CD) and 23 with adrenal Cushings 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.