title: Association of glucocorticoid receptor polymorphism A3669G with decreased risk of developing diabetes in patients with Cushing's syndrome.
abstract: OBJECTIVE
  Glucocorticoid receptor (GR) polymorphisms alter glucocorticoid (GC) sensitivity and have been associated with altered metabolic profiles. We evaluate the prevalence of the four GR (NR3C1) polymorphisms BclI, N363S, ER22/23EK, and A3669G in patients with Cushing's syndrome (CS) compared with healthy controls (HC) and we investigate their role in the development of metabolic abnormalities in patients with CS according to their hormonal profile.
  
  
  METHODS
  Sixty-one patients with CS and 71 sex- and age-matched HC were genotyped.
  
  
  RESULTS
  BclI variant was markedly higher in patients with CS compared with HC (62 vs 41%, P<0.05) while no significant differences were found among other polymorphisms. A very low frequency of N363S and the ER22/23EK was observed. In CS patients, despite the significantly increased levels of morning serum cortisol in BclI carriers compared with wild type no clinical or metabolic differences were found. In contrast, A3669G GR carriers showed a significantly reduced prevalence of type 2 diabetes mellitus compared with wild type (19 vs 68%, P=0.001) despite the higher levels of both serum morning (21.7±6 vs 27.3±8.6 μg/dl, P=0.009) and midnight cortisol (18.8±5.8 vs 24.0±8.0 μg/dl, P=0.01). The negative association between diabetes and A3669G GR polymorphism remained significant when data were adjusted for potential confounding factors.
  
  
  CONCLUSIONS
  The A3669G polymorphism of the GR gene plays a protective role in patients with CS, attenuating the effects of GC excess on glucose metabolism as shown by their reduced risk of diabetes.
authors: Division of Endocrinology, Polytechnic University of Marche, Via Conca 71, 60020 Torrette di Ancona, Italy.
authors: Laura
authors: L
authors: Trementino
authors: Gloria
authors: G
authors: Appolloni
authors: Carolina
authors: C
authors: Concettoni
authors: Marina
authors: M
authors: Cardinaletti
authors: Marco
authors: M
authors: Boscaro
authors: Giorgio
authors: G
authors: Arnaldi
mesh_terms: D000328:Adult; D003480:Cushing Syndrome / Q000150:complications* / Q000235:genetics*; D003920:Diabetes Mellitus / Q000209:etiology / Q000235:genetics*; D005260:Female; D005787:Gene Frequency / Q000235:genetics; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic / Q000235:genetics*; D011965:Receptors, Glucocorticoid / Q000235:genetics*
chemical_list: D011965:Receptors, Glucocorticoid