Identification of the BclI polymorphism in the glucocorticoid receptor gene: association with sensitivity to glucocorticoids in vivo and body mass index

Clin Endocrinol (Oxf). 2003 Nov;59(5):585-92. doi: 10.1046/j.1365-2265.2003.01888.x.


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.

Design and measurements: 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.

Subjects: 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Body Composition
  • Body Constitution
  • Body Mass Index
  • Deoxyribonucleases, Type II Site-Specific / genetics*
  • Dexamethasone*
  • Feedback, Physiological
  • Female
  • Glucocorticoids*
  • Heterozygote
  • Homozygote
  • Humans
  • Male
  • Polymorphism, Restriction Fragment Length
  • Receptors, Glucocorticoid / genetics*
  • Restriction Mapping
  • Sequence Analysis, DNA


  • Glucocorticoids
  • Receptors, Glucocorticoid
  • Dexamethasone
  • endodeoxyribonuclease BclI
  • Deoxyribonucleases, Type II Site-Specific