title: Analysis of BCLI, N363S and ER22/23EK Polymorphisms of the Glucocorticoid Receptor Gene in Adrenal Incidentalomas.
abstract: BACKGROUND
  Patients with adrenal incidentalomas (AI) may experience detrimental consequences due to a minimal cortisol excess sustained by adrenal adenoma. SNPs of the glucocorticoid receptor gene (NR3C1) modulate individual sensitivity to glucocorticoids and may interfere with the clinical presentation.
  
  
  OBJECTIVE
  To compare the frequency of N363S, ER22/23EK and BclI SNPs in patients with AI with the general population and to evaluate whether these SNPs are linked to consequences of cortisol excess.
  
  
  METHODS
  Multicentric, retrospective analysis of patients referred from 2010 to 2014 to 4 centers (Orbassano, Milano, Messina [Italy] and Zagreb [Croatia]).
  
  
  METHODS
  411 patients with AI; 153 males and 258 females and 186 from blood donors.
  
  
  METHODS
  All patients and controls were genotyped for BclI, N363S and ER22/23EK and SNPs frequency was associated with clinical and hormonal features.
  
  
  RESULTS
  SNP frequency was: SNP frequency was: N363S 5.4% (MAF 0.027), BclI 54.7% (MAF 0.328), ER22/23EK 4.4% (MAF 0.022), without any significant difference between patients and controls. N363S was more frequent in hypertensive patients (p = 0.03) and was associated with hypertension (p = 0.015) in patients with suppressed cortisol after the 1-mg DST.
  
  
  CONCLUSIONS
  Our results demonstrate that SNPs of the glucocorticoid receptor gene do not play a pathogenetic role for AI. The impact of any single SNP on the phenotypic expression of minimal cortisol excess is limited and their analysis does not provide additional data that may be exploited for patient management.
authors.affiliation: Internal Medicine 1, Department of Clinical and Biological Sciences, University of Turin, San Luigi Gonzaga Hospital, Orbassano, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Reimondo
authors.affiliation: Unit of Endocrinology and Metabolic Diseases, Fondazione IRCCS Cà Granda-Ospedale Maggiore Policlinico, Milano Department of Clinical Sciences and Community Health, University of Milan, Milan, Italy.
authors.forename: Iacopo
authors.initials: I
authors.lastname: Chiodini
authors.affiliation: Endocrine Unit, Department of Clinical and Experimental Medicine, University of Messina, Policlinico G. Martino Hospital, Messina, Italy.
authors.forename: Soraya
authors.initials: S
authors.lastname: Puglisi
authors.affiliation: Internal Medicine 1, Department of Clinical and Biological Sciences, University of Turin, San Luigi Gonzaga Hospital, Orbassano, Italy.
authors.forename: Anna
authors.initials: A
authors.lastname: Pia
authors.affiliation: Unit of Endocrinology and Metabolic Diseases, Fondazione IRCCS Cà Granda-Ospedale Maggiore Policlinico, Milano Department of Clinical Sciences and Community Health, University of Milan, Milan, Italy.
authors.forename: Valentina
authors.initials: V
authors.lastname: Morelli
authors.affiliation: Department of Endocrinology, University Hospital Zagreb, Zagreb, Croatia.
authors.forename: Darko
authors.initials: D
authors.lastname: Kastelan
authors.affiliation: Endocrine Unit, Department of Clinical and Experimental Medicine, University of Messina, Policlinico G. Martino Hospital, Messina, Italy.
authors.forename: Salvatore
authors.initials: S
authors.lastname: Cannavo
authors.affiliation: Statistical Unit, Department of Clinical and Biological Sciences, University of Turin, San Luigi Gonzaga, Hospital, Orbassano, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Berchialla
authors.affiliation: Medical Genetics, Department of Clinical and Biological Sciences, University of Turin, San Luigi Gonzaga Hospital, Orbassano, Italy.
authors.forename: Daniela
authors.initials: D
authors.lastname: Giachino
authors.affiliation: Internal Medicine 1, Department of Clinical and Biological Sciences, University of Turin, San Luigi Gonzaga Hospital, Orbassano, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Perotti
authors.affiliation: Medical Genetics, Department of Clinical and Biological Sciences, University of Turin, San Luigi Gonzaga Hospital, Orbassano, Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Cuccurullo
authors.affiliation: Internal Medicine 1, Department of Clinical and Biological Sciences, University of Turin, San Luigi Gonzaga Hospital, Orbassano, Italy.
authors.forename: Piero
authors.initials: P
authors.lastname: Paccotti
authors.affiliation: Unit of Endocrinology and Metabolic Diseases, Fondazione IRCCS Cà Granda-Ospedale Maggiore Policlinico, Milano Department of Clinical Sciences and Community Health, University of Milan, Milan, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Beck-Peccoz
authors.affiliation: Medical Genetics, Department of Clinical and Biological Sciences, University of Turin, San Luigi Gonzaga Hospital, Orbassano, Italy.
authors.forename: Mario
authors.initials: M
authors.lastname: De Marchi
authors.affiliation: Internal Medicine 1, Department of Clinical and Biological Sciences, University of Turin, San Luigi Gonzaga Hospital, Orbassano, Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Terzolo
mesh_terms: D000310:Adrenal Gland Neoplasms / Q000097:blood / Q000150:complications / Q000235:genetics*; D000311:Adrenal Glands / Q000378:metabolism / Q000473:pathology*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D006973:Hypertension / Q000097:blood / Q000150:complications / Q000235:genetics; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011965:Receptors, Glucocorticoid / Q000235:genetics*
chemical_list: C497713:NR3C1 protein, human; D011965:Receptors, Glucocorticoid; D006854:Hydrocortisone