title: BclI Glucocorticoid Receptor Polymorphism in Relation to Arterial Stiffening and Cardiac Structure and Function: The Hoorn and CODAM Studies.
abstract: BACKGROUND
  Chronic glucocorticoid excess is associated with arterial stiffening and cardiac dysfunction. The BclI glucocorticoid receptor (GR) polymorphism increases GR sensitivity and is associated with a higher body mass index (BMI) and some proxies for cardiovascular disease (CVD). Whether BclI influences arterial stiffening and cardiac dysfunction is currently unknown. Therefore, the aim of the present study was to investigate the association of the BclI polymorphism with arterial stiffening and cardiac structure and function.
  
  
  METHODS
  We conducted an observational cohort study, combining 2 cohort studies designed to investigate genetic and metabolic determinants of CVD. We genotyped 1,124 individuals (age: 64.7 ± 8.5 years) from the Hoorn study and Cohort on Diabetes and Atherosclerosis Maastricht (CODAM) study for BclI. Several arterial stiffening indices of the carotid (Hoorn and CODAM study), brachial and femoral artery and the carotid-femoral pulse wave velocity (Hoorn study only) were determined. In addition, in the Hoorn study, we determined several variables of cardiac structure and function.
  
  
  RESULTS
  We identified 155 homozygous carriers (GG), 498 heterozygous carriers (CG), and 471 noncarriers (CC) of the BclI polymorphism. BclI genotypes did not display significant differences in variables of arterial stiffening (e.g., carotid distensibility coefficient (DC): 12.41 ± 5.37 vs. 12.87 ± 5.55 10-3/kPa [mean ± SD]; P = 0.38; homozygous vs. noncarriers). In addition, no clear differences in estimates of cardiac structure and function were found.
  
  
  CONCLUSIONS
  Even though BclI is associated with a higher BMI and some proxies of CVD, our results do not support the concept that BclI carrier status is associated with greater arterial stiffening or cardiac dysfunction.
authors.affiliation: Department of Internal Medicine, Division of Endocrinology, Maastricht University Medical Center, Maastricht, The Netherlands.|Department of Human Biology and Human Movement Sciences, Maastricht University Medical Center, Maastricht, The Netherlands.|NUTRIM School for Nutrition and Translational Research in Metabolism, Maastricht University Medical Center, Maastricht, The Netherlands.
authors.forename: Dirk
authors.initials: D
authors.lastname: van Moorsel
authors.affiliation: Department of Internal Medicine, Maastricht University Medical Center, Maastricht, The Netherlands.|Heart and Vascular Center, Maastricht University Medical Center, Maastricht, The Netherlands.|CARIM School for Cardiovascular Diseases Maastricht, Maastricht University Medical Center, Maastricht, The Netherlands.
authors.forename: Ronald M
authors.initials: RM
authors.lastname: Henry
authors.affiliation: Department of Internal Medicine, Division of Endocrinology, Maastricht University Medical Center, Maastricht, The Netherlands.|CARIM School for Cardiovascular Diseases Maastricht, Maastricht University Medical Center, Maastricht, The Netherlands.|CAPHRI School for Public Health and Primary Care, Maastricht University Medical Center, Maastricht, The Netherlands.
authors.forename: Nicolaas C
authors.initials: NC
authors.lastname: Schaper
authors.affiliation: Department of Internal Medicine, Maastricht University Medical Center, Maastricht, The Netherlands.|CARIM School for Cardiovascular Diseases Maastricht, Maastricht University Medical Center, Maastricht, The Netherlands.
authors.forename: Marleen M
authors.initials: MM
authors.lastname: van Greevenbroek
authors.affiliation: Department of Internal Medicine, Division of Endocrinology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands.
authors.forename: Elisabeth F
authors.initials: EF
authors.lastname: van Rossum
authors.affiliation: Department of Molecular Cell Biology, Leiden University Medical Center, Leiden, The Netherlands.|Section Molecular Epidemiology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Leen M
authors.initials: LM
authors.lastname: 't Hart
authors.affiliation: Department of Internal Medicine, Maastricht University Medical Center, Maastricht, The Netherlands.|CARIM School for Cardiovascular Diseases Maastricht, Maastricht University Medical Center, Maastricht, The Netherlands.
authors.forename: Casper G
authors.initials: CG
authors.lastname: Schalkwijk
authors.affiliation: Department of Internal Medicine, Maastricht University Medical Center, Maastricht, The Netherlands.|CARIM School for Cardiovascular Diseases Maastricht, Maastricht University Medical Center, Maastricht, The Netherlands.
authors.forename: Carla J
authors.initials: CJ
authors.lastname: van der Kallen
authors.affiliation: Department of Epidemiology and Biostatistics and the EMGO Institute for Health and Care Research, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Jacqueline M
authors.initials: JM
authors.lastname: Dekker
authors.affiliation: Department of Internal Medicine, Maastricht University Medical Center, Maastricht, The Netherlands.|CARIM School for Cardiovascular Diseases Maastricht, Maastricht University Medical Center, Maastricht, The Netherlands.
authors.forename: Coen D
authors.initials: CD
authors.lastname: Stehouwer
authors.affiliation: Department of Internal Medicine, Division of Endocrinology, Maastricht University Medical Center, Maastricht, The Netherlands.|Department of Human Biology and Human Movement Sciences, Maastricht University Medical Center, Maastricht, The Netherlands.|NUTRIM School for Nutrition and Translational Research in Metabolism, Maastricht University Medical Center, Maastricht, The Netherlands.
authors.forename: Bas
authors.initials: B
authors.lastname: Havekes
mesh_terms: D000328:Adult; D015992:Body Mass Index; D015331:Cohort Studies; D003430:Cross-Sectional Studies; D005260:Female; D019940:Genes, bcl-1 / Q000235:genetics*; D005838:Genotype; D006321:Heart / Q000503:physiopathology*; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D009206:Myocardium / Q000473:pathology*; D011110:Polymorphism, Genetic / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D063177:Pulse Wave Analysis; D059289:Vascular Stiffness / Q000235:genetics*
keywords: BclI; arterial stiffening; arterial stiffness; blood pressure; cardiac function; cardiac structure; glucocorticoid receptor; glucocorticoid receptor polymorphism; glucocorticoids; hypertension; left ventricular function; rs41423247.