Endocrine Abstracts (2006) 11 P533

N363S and BclI variants in the glucocorticoid receptor gene and their associations in Cushing’s syndrome and Addison’s disease

GA Giorgio Arnaldi, GA Gloria Appolloni, CP Claudia Polloni, PR Paola Romagni, BP Barbara Polenta, MC Marina Cardinaletti, AF Alberto Falorni & MB Marco Boscaro

Division if Endocrinology, Institute of Clinical Medicine and Applied Biotechnology, Ancona/Marche, Italy.

Objective: Interindividual variation in glucocorticoid sensitivity can be partly explained by polymorphisms in the GC receptor gene. The most frequent polymorphisms of the GR gene (N363S and BclI) are associated with increased BMI, less lean mass, higher cholesterol and insulin levels. In the present study we investigated the role of the N363S and the BclI polymorphisms in patients with adrenal disease to evaluate their prevalence and the possible clinic and hormone correlations.

Patients and method: We studied a cohort of 156 patients divided into three groups. Group I: 44 patients with Cushing’s syndrome. Group II: 40 patients with Addison’s disease; Group III: 72 healthy subjects. In order to identify genetic variations, the GR gene was screened for nucleotide variations using a PCR and digestion.

Results: In the cohort of 156 patients, 3 subjects (two control and one with Cushing’s syndrome) were heterozygous for the N363S variant (allelic frequency 1%). For the BclI variant, 61 subjects were heterozygous and 15 subjects were homozygous (allelic frequency 30%). The frequency of these polymorphisms is not statistically different within the three groups. In patients with Cushing’s syndrome, the G allele of Bcl I polymorphism, was associated with increased BMI, blood pressure, and elevated total cholesterol/HDL ratio (P<0.05). Within the three groups, only a patient with Cushing’s disease was positive for both polymorphisms.

Conclusions: These preliminary results suggest that there is not a prevalence of these polymorphisms in patients with Cushing’s syndrome and Addison disease regarding to healthy subjects.

Furthermore, these data confirm that the BclI polymorphism is associated with an increased sensitivity to glucocorticoids as well as cardiovascular risk.