title: A functional polymorphism in the glucocorticoid receptor gene and its relation to cardiovascular disease risk in familial hypercholesterolemia.
abstract: BACKGROUND
  Individuals with the functional ER22/23EK variant in the glucocorticoid receptor gene are relatively resistant to the downstream consequences of glucocorticoids. Evidence suggests that carriers have a more favorable cardiovascular risk profile, but the relationship between this ER22/23EK variant and cardiovascular disease has not been hitherto assessed.
  
  
  OBJECTIVE
  We, therefore, determined whether carriership of the ER22/23EK improves cardiovascular disease risk in patients with severe hypercholesterolemia.
  
  
  METHODS
  In a multicenter cohort study, 2024 patients with heterozygous familial hypercholesterolemia, aged 18 yr and older, were genotyped for the ER22/23EK polymorphism. Patients were identified at lipid clinics throughout The Netherlands between 1989 and 2002.
  
  
  METHODS
  The primary outcome measure was cardiovascular disease.
  
  
  RESULTS
  Seventy-six (7.8%) of 977 men and 72 (6.9%) of 1047 women were carriers of the ER22/23EK variant. A total of 395 men and 247 women had a cardiovascular event. In contrast to expected results, we observed no significant association of the ER22/23EK variant with cardiovascular disease risk (men: relative risk, 0.75; 95% confidence interval, 0.50-1.14; P = 0.2; women: relative risk, 1.37; 95% confidence interval, 0.82-2.28; P = 0.2). However, we found a significant interaction between gender and the polymorphism on cardiovascular disease (P = 0.02).
  
  
  CONCLUSIONS
  In this large cohort of individuals with very high risk of cardiovascular disease, the association between the functional ER22/23EK polymorphism and cardiovascular risk was not significant overall, although it varied significantly by gender.
authors.affiliation: Department of Internal Medicine, D435, Erasmus Medical Center, P.O. Box 2040, 3000 AC Rotterdam, The Netherlands.
authors.forename: Kristel C M C
authors.initials: KC
authors.lastname: Koeijvoets
authors.forename: Elisabeth F C
authors.initials: EF
authors.lastname: van Rossum
authors.forename: Geesje M
authors.initials: GM
authors.lastname: Dallinga-Thie
authors.forename: Ewout W
authors.initials: EW
authors.lastname: Steyerberg
authors.forename: Joep C
authors.initials: JC
authors.lastname: Defesche
authors.forename: John J P
authors.initials: JJ
authors.lastname: Kastelein
authors.forename: Steven W J
authors.initials: SW
authors.lastname: Lamberts
authors.forename: Eric J G
authors.initials: EJ
authors.lastname: Sijbrands
mesh_terms: D000328:Adult; D000368:Aged; D002318:Cardiovascular Diseases / Q000209:etiology*; D015331:Cohort Studies; D005260:Female; D006801:Humans; D006938:Hyperlipoproteinemia Type II / Q000150:complications / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D011965:Receptors, Glucocorticoid / Q000235:genetics*; D012189:Retrospective Studies; D012307:Risk Factors
chemical_list: D011965:Receptors, Glucocorticoid