title: Identification of the BclI polymorphism in the glucocorticoid receptor gene: association with sensitivity to glucocorticoids in vivo and body mass index.
abstract: OBJECTIVE
  Sensitivity to glucocorticoids differs between individuals, partially due to genetic variation in the glucocorticoid receptor (GR) gene. We studied the sequence alteration of a previously described intronic BclI polymorphism of the GR gene, and investigated whether there was an association with sensitivity to glucocorticoids and anthropometric parameters in a group of healthy elderly individuals.
  
  
  METHODS
  In study group 1, two overnight dexamethasone suppression tests (DSTs) were performed: with 1 mg dexamethasone, and 2.5 years later with 0.25 mg dexamethasone. Anthropometric parameters were measured in a larger population (study group 2), as well as in a third study group, in which we also measured body composition by dual-energy X-ray absorbtiometry (DEXA) scans.
  
  
  METHODS
  Groups 1 and 2, respectively, 191 and 1963 male and female participants of the Rotterdam study, a population-based study in Dutch elderly. Study group 3: 370 elderly males (mean age 77.8 +/- 0.2 years) from Zoetermeer, the Netherlands.
  
  
  RESULTS
  We identified the BclI restriction site polymorphism as a C/G substitution in intron 2, 646 nucleotides downstream from exon 2. After both 1 mg and 0.25 mg DST, heterozygous (CG) and homozygous G-allele carriers (GG) had lower cortisol levels than CC-carriers (P = 0.01 and P = 0.02, respectively). In study group 2, we found a lower body mass index (BMI; P = 0.006) and waist-hip ratio (WHR; P = 0.02) in G-allele carriers. In study group 3, again we found a lower BMI (P = 0.05) in G-allele carriers. No differences were found in fat mass. However, lean mass tended to be lower in G-allele carriers (P = 0.07).
  
  
  CONCLUSIONS
  We characterized a BclI-RFLP (restriction fragment length polymorphism) of the GR gene as a C/G polymorphism in intron 2 of which the G-allele was associated with hypersensitivity to glucocorticoids. This resulted in a lower BMI in older individuals in general, while our study in elderly males suggests that the lower BMI is probably due to a greater loss of lean mass during the ageing process.
authors: Department of Internal Medicine, Erasmus Medical Center, Rotterdam The Netherlands.
authors: Elisabeth F C
authors: EF
authors: van Rossum
authors: Jan W
authors: JW
authors: Koper
authors: Annewieke W
authors: AW
authors: van den Beld
authors: André G
authors: AG
authors: Uitterlinden
authors: Pascal
authors: P
authors: Arp
authors: Wietske
authors: W
authors: Ester
authors: Joop A M J L
authors: JA
authors: Janssen
authors: Albert O
authors: AO
authors: Brinkmann
authors: Frank H
authors: FH
authors: de Jong
authors: Diederick E
authors: DE
authors: Grobbee
authors: Huibert A P
authors: HA
authors: Pols
authors: Steven W J
authors: SW
authors: Lamberts
mesh_terms: D000368:Aged; D001823:Body Composition; D001824:Body Constitution; D015992:Body Mass Index; D015252:Deoxyribonucleases, Type II Site-Specific / Q000235:genetics*; D003907:Dexamethasone; D025461:Feedback, Physiological; D005260:Female; D005938:Glucocorticoids; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D008297:Male; D012150:Polymorphism, Restriction Fragment Length; D011965:Receptors, Glucocorticoid / Q000235:genetics*; D015183:Restriction Mapping; D017422:Sequence Analysis, DNA
chemical_list: D005938:Glucocorticoids; D011965:Receptors, Glucocorticoid; D003907:Dexamethasone; C041666:endodeoxyribonuclease BclI; D015252:Deoxyribonucleases, Type II Site-Specific