BclI polymorphism of the glucocorticoid receptor gene is associated with increased bone resorption in patients on glucocorticoid replacement therapy

KR Koetz, Liesbeth van Rossum, M Ventz, S Diederich, M Quinkler

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23 Citations (Scopus)

Abstract

Context Patients with primary adrenal insufficiency (PAI) and patients with congenital adrenal hyperplasia (CAH) receive weight-adapted standard glucocorticoid replacement therapy. Clinically, some patients appear more sensitive to therapeutic administration of glucocorticoids than others. Glucocorticoid sensitivity is at least partially genetically determined by polymorphisms of the glucocorticoid receptor (GR) and might influence bone mineral density (BMD). Objectives To determine if bone turnover markers and BMD are associated with the GR gene polymorphism BclI in patients with PAI and CAH. Design and Patients A prospective, cross-sectional study including 74 PAI and 38 CAH patients. BMD was evaluated by DXA. Serum levels of bone turnover markers, minerals, vitamins and hormones, and urinary crosslinks were measured. Results Patients carrying the homozygous BclI polymorphism (GG) had significantly higher serum -CrossLaps (0 center dot 37 +/- 0 center dot 34g/l; P<0 center dot 05) and urinary collagen crosslinks (NTX, 68 center dot 1 +/- 32 center dot 4nmol/g; P<0 center dot 005) despite receiving the lowest average daily hydrocortisone dose of 9 center dot 9 +/- 3 center dot 7mg/m2 (P<0 center dot 05). The GG genotype occurred significantly more frequently in patients with increased NTX (OR=6 center dot 7, 95% CI=1 center dot 7825 center dot 38) than in patients with normal NTX. However, BMD was not significantly different between different allelic variants. No significant differences in associations of the genotypes with outcomes (or in clinical characteristics) were found between the sexes. Conclusions Although the sample sizes were relatively small and the results should be interpreted with caution, this study suggests that the homozygous (GG) genotype may be associated with higher bone resorption in adult PAI and CAH patients. GG-carriers needed a lower hydrocortisone dose on average supporting the concept that this GR variant is associated with increased cortisol sensitivity.
Original languageUndefined/Unknown
Pages (from-to)831-837
Number of pages7
JournalClinical Endocrinology
Volume78
Issue number6
DOIs
Publication statusPublished - 2013

Research programs

  • EMC MM-01-39-01

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