Body composition and bone mineral density in women with Cushing's syndrome in remission and the association with common genetic variants influencing glucocorticoid sensitivity
2014
Objective: Adverse body compositional features and low bone mineral density (BMD) are the characteristic of patients with active Cushing's syndrome (CS). The aim of this study was to evaluate body composition and BMD in women with CS in long-term remission and the influence of polymorphisms in genes affecting glucocorticoid (GC) sensitivity on these end-points. Design, patients and methods: This was a cross-sectional, case-controlled study, including 50 women previously treated for CS and 50 age and gender-matched controls. Median (interquartile range) remission time was 13 (5-19) years. Body composition and BMD were measured with dual-energy X-ray absorptiometry. Five polymorphisms in four genes associated with GC sensitivity were analysed using TaqMan or Sequenom single-nucleotide polymorphism genotyping. Results: Patients with CS in remission had increased abdominal fat mass (P!0.01), whereas BMD was not significantly different at any site between patients and controls. In patients, the NR3C1 Bcl1 polymorphism was associated with reduced total (P!0.05) and femur neck BMD (P!0.05). The polymorphism rs1045642 in the ABCB1 gene was associated with increased abdominal fat mass (P!0.05) and decreased appendicular skeletal muscle mass (P!0.05). GC replacement was associated with reduced total BMD (P!0.01), BMD at lumbar spine (P!0.05) and increased abdominal fat (P!0.01). Conclusion: Ongoing GC replacement therapy together with polymorphisms in two genes related with GC sensitivity is associated with abdominal obesity and adverse skeletal health in patients with CS in long-term remission.
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