ECE2017 Eposter Presentations: Calcium and Bone Steroid metabolism + action (1 abstracts)
Genetic variations in the HSD11B1 gene in patients treated with glucocorticoids show associations with bone mineral density
Heide Siggelkow 1, , Martina Blaschke 1, , Gabriele Armbrecht 3 , Friederike Thomasius 3 , Oliver Bock 3 , Mladen Tzvetkov 4 , Claus-C Glüer 5 & Dieter Felsenberg 3
1Clinic of Gastroenterology and Gastrointestinal Oncology, University Medical Center, Göttingen, Germany; 2MVZ Endokrinologikum, Göttingen, Germany; 3Center for Muscle and Bone Research, Charite, Berlin, Germany; 4Institute of Clinical Pharmacology, University Medical Center Göttingen, Göttingen, Germany; 5Section Biomedical Imaging, Department of Radiology and Neuroradiology, MOINCC, Kiel, Germany.
Introduction: Physiological glucocorticoids play an essential role in bone formation but can cause osteoporosis if present in excess. The key enzyme converting inactive cortisone into the active cortisol and vice versa is 11-beta-hydroxy-steroid-dehydrogenase (11β-HSD1). We have reported that genetic variations in the HSD11B1 gene correlate with increased cortisol levels in dexamethasone suppression and with changes in bone mineral density (BMD) suggesting individual differences in 11β-HSD1 activity caused by polymorphisms. In this study we investigated the effect of HSD11B1 SNPs on BMD in patients on glucocorticoid therapy.
Methods: In 246 patients treated with different glucocorticoids the HSD11B1 SNPs rs11811440, rs1000283 und rs932335 were determined. Patients received glucocorticoids due to rheumatoid arthritis or asthma (64%), or other rheumatic, gastrointestinal or pulmonary disorders. An equivalent glucocorticoid dose was calculated for the different glucocorticoids used. BMD of the spine or femoral neck, and the number of fractures and falls were correlated to the HSD11B1 SNPs.
Results: BMD, the number of fractures and falls did not show an association with daily or cumulative equivalent dose or type of glucocorticoid. Since the three genetically linked SNPs in intron 5 of the 11β-HSD1 gene – rs11811440, rs1000283, and rs932335 HSD11B1 highly correlated, only rs11811440 was further analyzed. In patients treated with the glucocorticoids prednisolone or methylprednisolone the presence of the A-allele was associated with lower BMD levels.
Discussion: Our results suggest that in patients treated with glucocorticoids the function of 11β-HSD1 is dependent on HSD11B1 polymorphisms. Hence, inactivation of prednisolone or methylprednisolone by 11β-HSD1 would be the crucial step for BMD levels in glucocorticoid-treated individuals.
Volume 49
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Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
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