title: BClI polymorphism of the glucocorticoid receptor gene is associated with increased obesity, impaired glucose metabolism and dyslipidaemia in patients with Addison's disease.
abstract: OBJECTIVE
  Although glucocorticoids are essential for health, several studies have shown that glucocorticoids replacement in Addison's disease might be involved in anthropometric and metabolic impairment, with increased cardiovascular risk, namely if conventional doses are used. As the effects of glucocorticoids are mediated by the glucocorticoid receptor, encoded by NR3C1 gene, different polymorphisms in the NR3C1 gene have been linked to altered glucocorticoid sensitivity in general population as well as in patients with obesity or metabolic syndrome.
  
  
  METHODS
  We investigated the impact of glucocorticoid receptor gene polymorphisms, including the BclI, N363S and ER22/23EK variants, on anthropometric parameters (BMI and waist circumference), metabolic profile (HOMA, OGTT and serum lipids) and ACTH levels in 50 patients with Addison's disease (34 women and 16 men, age 20-82 year) under glucocorticoids replacement.
  
  
  RESULTS
  Neither N363S nor ER22/23EK variants were significantly associated with anthropometric, metabolic or hormonal parameters, while patients carrying the homozygous BclI polymorphism GG (n = 4) showed higher (P < 0·05) BMI, waist circumference, HOMA and 2-h glucose levels after OGTT, as well as total cholesterol and triglycerides than those with wild-type genotype CC (n = 28) or heterozygous CG (n = 18). The totality of GG patients was connoted by abdominal adiposity, impaired glucose tolerance/diabetes mellitus or dyslipidaemia, while a lower percentage of CC or CG patients showed some anthropometric and metabolic alterations.
  
  
  CONCLUSIONS
  These results suggest that BclI polymorphism may influence the sensitivity to glucocorticoids in patients with Addison's disease and may contribute, along with other factors, to the increase in central adiposity, impaired glucose metabolism and dyslipidaemia.
authors.affiliation: Department of Clinical and Biological Sciences, University of Turin, Turin, Italy.
authors.forename: Roberta
authors.initials: R
authors.lastname: Giordano
authors.forename: Stefania
authors.initials: S
authors.lastname: Marzotti
authors.forename: Rita
authors.initials: R
authors.lastname: Berardelli
authors.forename: Ioannis
authors.initials: I
authors.lastname: Karamouzis
authors.forename: Annalisa
authors.initials: A
authors.lastname: Brozzetti
authors.forename: Valentina
authors.initials: V
authors.lastname: D'Angelo
authors.forename: Giulio
authors.initials: G
authors.lastname: Mengozzi
authors.forename: Giorgia
authors.initials: G
authors.lastname: Mandrile
authors.forename: Daniela
authors.initials: D
authors.lastname: Giachino
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Migliaretti
authors.forename: Vittorio
authors.initials: V
authors.lastname: Bini
authors.forename: Alberto
authors.initials: A
authors.lastname: Falorni
authors.forename: Ezio
authors.initials: E
authors.lastname: Ghigo
authors.forename: Emanuela
authors.initials: E
authors.lastname: Arvat
mesh_terms: D000224:Addison Disease / Q000188:drug therapy / Q000235:genetics*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000886:Anthropometry; D001327:Autoimmune Diseases; D004247:DNA / Q000097:blood; D004351:Drug Resistance / Q000235:genetics; D050171:Dyslipidemias / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D005938:Glucocorticoids / Q000276:immunology / Q000627:therapeutic use; D018149:Glucose Intolerance / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000235:genetics*; D011110:Polymorphism, Genetic / Q000235:genetics*; D011965:Receptors, Glucocorticoid / Q000235:genetics*; D012189:Retrospective Studies
chemical_list: D005938:Glucocorticoids; C497713:NR3C1 protein, human; D011965:Receptors, Glucocorticoid; D004247:DNA