title: Glucocorticoid receptor polymorphisms modulate cardiometabolic risk factors in patients in long-term remission of Cushing's syndrome.
abstract: BACKGROUND
  Glucocorticoid receptor (GR) polymorphisms modulate glucocorticoid (GC) sensitivity and are associated with altered metabolic profiles.
  
  
  OBJECTIVE
  To evaluate the presence of GR polymorphisms (BclI (rs41423247), N363S (rs56149945), ER22/23EK (rs6189/rs6190), and 9β (rs6198) and investigate their associations with metabolic alterations in patients in long-term remission of Cushing's syndrome (CS).
  
  
  METHODS
  Cross-sectional case-control study.
  
  
  METHODS
  Sixty patients in long-term remission of CS were genotyped. Associations between GR polymorphisms and multiple vascular, body composition and metabolic parameters were investigated.
  
  
  METHODS
  Allelic frequencies of the polymorphisms and their associations with several cardiometabolic risk factors.
  
  
  RESULTS
  This study shows that carriers of the 9β polymorphism have a higher systolic blood pressure and lower resistin levels. The GC sensitizing BclI polymorphism is associated with an adverse cardiometabolic risk factor profile: higher fat percentages of extremities and legs, higher serum leptin and E-selectin levels, and higher intima media thickness in carriers versus non-carriers.
  
  
  CONCLUSIONS
  The 9β and BclI polymorphisms of the GR adversely affect the cardiometabolic profile in patients who are in remission after the treatment of CS. This suggests that genetically altered GC sensitivity modulates the long-term adverse cardiometabolic effects resulting from (endogenous) hypercortisolism.
authors.affiliation: Division of Endocrinology, Department of Medicine, Radboud University Medical Centre, Geert Grooteplein 8, PO Box 9101, 6500 HB, Nijmegen, The Netherlands. sean.roerink@radboudumc.nl.
authors.forename: Sean H P P
authors.initials: SH
authors.lastname: Roerink
authors.affiliation: Division of Endocrinology, Department of Medicine, Radboud University Medical Centre, Geert Grooteplein 8, PO Box 9101, 6500 HB, Nijmegen, The Netherlands.
authors.forename: M A E M
authors.initials: MA
authors.lastname: Wagenmakers
authors.affiliation: Division of Endocrinology, Department of Medicine, Radboud University Medical Centre, Geert Grooteplein 8, PO Box 9101, 6500 HB, Nijmegen, The Netherlands.
authors.forename: J W A
authors.initials: JW
authors.lastname: Smit
authors.affiliation: Division of Endocrinology, Department of Internal Medicine, Erasmus University Medical Center Rotterdam, 's-Gravendijkwal 230, 3015 CE, Rotterdam, The Netherlands.
authors.forename: E F C
authors.initials: EF
authors.lastname: van Rossum
authors.affiliation: Division of Endocrinology, Department of Medicine, Radboud University Medical Centre, Geert Grooteplein 8, PO Box 9101, 6500 HB, Nijmegen, The Netherlands.
authors.forename: R T
authors.initials: RT
authors.lastname: Netea-Maier
authors.affiliation: Division of Endocrinology, Department of Medicine, Radboud University Medical Centre, Geert Grooteplein 8, PO Box 9101, 6500 HB, Nijmegen, The Netherlands.
authors.forename: T S
authors.initials: TS
authors.lastname: Plantinga
authors.affiliation: Division of Endocrinology, Department of Medicine, Radboud University Medical Centre, Geert Grooteplein 8, PO Box 9101, 6500 HB, Nijmegen, The Netherlands.
authors.forename: A R M M
authors.initials: AR
authors.lastname: Hermus
mesh_terms: D050154:Adiposity / Q000235:genetics*; D000328:Adult; D000483:Alleles; D001794:Blood Pressure / Q000235:genetics*; D059168:Carotid Intima-Media Thickness; D016022:Case-Control Studies; D003430:Cross-Sectional Studies; D003480:Cushing Syndrome / Q000097:blood / Q000235:genetics*; D019040:E-Selectin / Q000097:blood; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D020738:Leptin / Q000097:blood; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011965:Receptors, Glucocorticoid / Q000235:genetics*; D052243:Resistin / Q000097:blood; D012307:Risk Factors
chemical_list: D019040:E-Selectin; D020738:Leptin; D011965:Receptors, Glucocorticoid; D052243:Resistin
keywords: Cushing’s syndrome; Genetic predisposition; Glucocorticoid receptor polymorphisms; Long-term remission; Metabolic profile