title: Common genetic variants in the glucocorticoid receptor and the 11β-hydroxysteroid dehydrogenase type 1 genes influence long-term cognitive impairments in patients with Cushing's syndrome in remission.
abstract: BACKGROUND
  Cognitive function is impaired in patients with Cushing's syndrome (CS) in remission.
  
  
  OBJECTIVE
  The objective of the investigation was to study the effects of polymorphisms in genes associated with glucocorticoid (GC) sensitivity on cognitive function in patients with CS in long-term remission.
  
  
  METHODS
  This was a cross-sectional, case-controlled, single-center study.
  
  
  METHODS
  Fifty-three patients with CS in remission and 53 controls matched for age, gender, and educational level participated in the study.
  
  
  METHODS
  Cognitive function, studied using standardized neuropsychological testing, and polymorphisms in the GC receptor (NR3C1; Bcl1 and A3669G), mineralocorticoid receptor (NR3C2; I180V), 11β-hydroxysteroid dehydrogenase type 1 (11βHSD1; rs11119328), and ATP binding cassette B1 (ABCB1; rs1045642) genes were measured. The association between cognitive function and polymorphisms were analyzed using linear regression with adjustments for age and educational level.
  
  
  RESULTS
  The mean age in patients and controls was 53 ± 14 years. The median (interquartile range) duration of remission was 13 (5-18) years. In patients, the single-nucleotide polymorphism rs11119328 was associated with impairments in processing speed, auditory attention, auditory working memory, and reading speed. This association was not seen in matched controls. The Bcl1 polymorphism was associated with fatigue and worse visual attention and working memory. The remaining single-nucleotide polymorphisms were not associated with cognitive performance.
  
  
  CONCLUSIONS
  In this study, polymorphisms in the 11βHSD1 and NR3C1 genes were associated with impaired cognitive function, indicating that GC sensitivity and prereceptor regulation of GC action may play a role in the long-term consequences of CS. The study provides a novel insight into the etiology of cognitive dysfunction in patients with CS in remission.
authors.affiliation: Institute of Medicine (O.R., C.A.M.G., R.B., G.J.), Institute of Neuroscience and Physiology (P.B.), and Vigilance and Neurocognition Laboratory (D.N.E.), Sahlgrenska Academy, University of Gothenburg, SE-413 45 Göteborg Sweden.
authors.forename: Oskar
authors.initials: O
authors.lastname: Ragnarsson
authors.forename: Camilla A M
authors.initials: CA
authors.lastname: Glad
authors.forename: Peter
authors.initials: P
authors.lastname: Berglund
authors.forename: Ragnhildur
authors.initials: R
authors.lastname: Bergthorsdottir
authors.forename: Derek N
authors.initials: DN
authors.lastname: Eder
authors.forename: Gudmundur
authors.initials: G
authors.lastname: Johannsson
mesh_terms: D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1 / Q000235:genetics*; D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D003071:Cognition / Q000502:physiology; D003072:Cognition Disorders / Q000209:etiology / Q000235:genetics*; D003430:Cross-Sectional Studies; D003480:Cushing Syndrome / Q000150:complications / Q000235:genetics* / Q000628:therapy; D005260:Female; D014644:Genetic Variation; D006801:Humans; D008297:Male; D008875:Middle Aged; D011965:Receptors, Glucocorticoid / Q000235:genetics*; D018161:Receptors, Mineralocorticoid / Q000235:genetics; D012074:Remission Induction
chemical_list: C497713:NR3C1 protein, human; C561839:NR3C2 protein, human; D011965:Receptors, Glucocorticoid; D018161:Receptors, Mineralocorticoid; D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1