title: Role of glucocorticoid receptor polymorphism in adrenal incidentalomas.
abstract: BACKGROUND
  Adrenal incidentalomas (AI) have been associated with and an increased prevalence of metabolic and bone complications. The N363S and BclI polymorphisms of the glucocorticoid receptor (GR) have been associated with an increased sensitivity to glucocorticoid (GC). This observational study aims to evaluate whether BclI and N363S polymorphisms play a role in the development of complications in AI.
  
  
  METHODS
  We enrolled 100 patients with AI (66 F; 34M). The presence of diabetes, arterial hypertension (AH), dyslipidaemia, osteoporosis and vertebral fracture (Fx), waist circumference and the Body Mass Index (BMI) were assessed. DNA samples were genotyped. Patients with wild-type BclI, wild-type N363S and heterozygous BclI polymorphism were classified as carriers of haplotype 1 (H1; n = 86), patients with homozygous BclI and heterozygous N363S polymorphism of GR of haplotype 2 (H2; n = 14).
  
  
  RESULTS
  We found no clinical or biochemical differences between haplotype 1 and 2 groups, but a higher prevalence of the simultaneous presence of Fx plus AH in H2 patients (H2 n = 7, H1 n = 16, P = 0.01). Logistic regression analysis showed that the presence of Fx and of AH and the combination of the presence of Fx plus AH were associated with the H2 genotype regardless of the degree of cortisol secretion, age, BMI and BMD (OR 4.88, 95%CI 1.47-18.40, P = 0.05; OR 8.25, 95%CI 0.98-69.52, P = 0.05; OR 7.25, 95%CI 1.57-35.78, P = 0.011; respectively).
  
  
  CONCLUSIONS
  In AI patients, the presence of the haplotype 2 of BclI and N363S is associated with the presence of AH, Fx and with the combination of Fx and AH.
authors.affiliation: Unit of Endocrinology and Diabetology, Department of Medical Sciences, University of Milan, Fondazione IRCCS Ca' Granda - Ospedale Maggiore Policlinico, Milan, Italy.
authors.forename: Valentina
authors.initials: V
authors.lastname: Morelli
authors.forename: Francesca
authors.initials: F
authors.lastname: Donadio
authors.forename: Cristina
authors.initials: C
authors.lastname: Eller-Vainicher
authors.forename: Valentina
authors.initials: V
authors.lastname: Cirello
authors.forename: Luca
authors.initials: L
authors.lastname: Olgiati
authors.forename: Chiara
authors.initials: C
authors.lastname: Savoca
authors.forename: Elisa
authors.initials: E
authors.lastname: Cairoli
authors.forename: Antonio Stefano
authors.initials: AS
authors.lastname: Salcuni
authors.forename: Paolo
authors.initials: P
authors.lastname: Beck-Peccoz
authors.forename: Iacopo
authors.initials: I
authors.lastname: Chiodini
mesh_terms: D000236:Adenoma / Q000150:complications / Q000235:genetics*; D000310:Adrenal Gland Neoplasms / Q000150:complications / Q000235:genetics*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001665:Binding Sites / Q000235:genetics; D003920:Diabetes Mellitus / Q000453:epidemiology; D050171:Dyslipidemias / Q000453:epidemiology; D005260:Female; D050723:Fractures, Bone / Q000453:epidemiology; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D006973:Hypertension / Q000453:epidemiology; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D010024:Osteoporosis / Q000453:epidemiology; D011110:Polymorphism, Genetic; D015995:Prevalence; D011965:Receptors, Glucocorticoid / Q000235:genetics*; D013131:Spine
chemical_list: D011965:Receptors, Glucocorticoid