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BclI polymorphism of the glucocorticoid receptor gene is associated with increased bone resorption in patients on glucocorticoid replacement therapy.
MedLine Citation:
PMID:  23134110     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
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 β-CrossLaps (0.37 ± 0.34 μg/l; p<0.05) and urinary collagen crosslinks (NTX, 68.1 ± 32.4 nmol/g; p<0.005) despite receiving the lowest average daily hydrocortisone dose of 9.9 ± 3.7 mg/m(2) (p<0.05). The GG genotype occurred significantly more frequently in patients with increased NTX (OR=6.7, CI 95%=1.78-25.38) 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. © 2012 Blackwell Publishing Ltd.
Authors:
Kathrin R Koetz; Elisabeth F C van Rossum; Manfred Ventz; Sven Diederich; Marcus Quinkler
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-11-8
Journal Detail:
Title:  Clinical endocrinology     Volume:  -     ISSN:  1365-2265     ISO Abbreviation:  Clin. Endocrinol. (Oxf)     Publication Date:  2012 Nov 
Date Detail:
Created Date:  2012-11-8     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0346653     Medline TA:  Clin Endocrinol (Oxf)     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
© 2012 Blackwell Publishing Ltd.
Affiliation:
Department of Clinical Endocrinology, Charité Campus Mitte, Charité University Medicine Berlin, Germany.
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