The association of glucocorticoid receptor polymorphism with metabolic outcomes in menopausal women with adrenal incidentalomas
| Autor: | Tatjana Isailovic, Bojana Popovic, Jadranka Antic, Tamara Bogavac, Sanja Ognjanovic, Tatjana Pekmezovic, Djuro Macut, Valentina Elezovic Kovacevic, Ivana Božić Antić, Milica Opalic, Dusan Ilic |
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| Rok vydání: | 2021 |
| Předmět: |
Adult
Hypothalamo-Hypophyseal System medicine.medical_specialty Hydrocortisone Adrenal Gland Neoplasms Pituitary-Adrenal System Adipose tissue 030209 endocrinology & metabolism 030204 cardiovascular system & hematology Polymorphism Single Nucleotide General Biochemistry Genetics and Molecular Biology Impaired glucose tolerance 03 medical and health sciences Receptors Glucocorticoid 0302 clinical medicine Insulin resistance Glucocorticoid Sensitivity Glucocorticoid receptor Polymorphism (computer science) Internal medicine Humans Medicine Aged business.industry Obstetrics and Gynecology Middle Aged medicine.disease Genes bcl-1 3. Good health Cross-Sectional Studies Endocrinology Diabetes Mellitus Type 2 Lean body mass Female Menopause business Glucocorticoid medicine.drug |
| Zdroj: | Maturitas. 151:15-21 |
| ISSN: | 0378-5122 |
| Popis: | Objectives To investigate whether BclI polymorphism in the glucocorticoid receptor gene influences hypothalamic-pituitary-adrenal (HPA) axis regulation, body composition and metabolic parameters in women with adrenal incidentalomas (AIs). Study design A cross-sectional study. Main outcome measures We analyzed 106 women with AIs. Insulin resistance was assessed using a homeostasis model while HPA activity was assessed using dexamethasone suppression tests (DST), basal ACTH, urinary free cortisol, and midnight serum cortisol level. Body composition was analyzed using dual-energy X-ray absorptiometry. DNA was obtained from peripheral blood leucocytes and BclI polymorphism was detected using PCR, RFLP and DNA sequencing. Results BclI carriers in comparison with those with wild-type BclI had less suppressed cortisol after DST-0.5 mg (126.4 ± 111.4 vs 80.9 ± 75.7 nmol/l, p = 0.026) and had a lower prevalence of impaired glucose tolerance and of type 2 diabetes mellitus (T2DM). BclI carriers had a higher percentage of leg fat mass (FM), lower left-sided limb muscle mass and a decline in total lean body mass. Duration of menopause remained a strong predictor of appendicular lean mass index (ALMI) (β=-0.125, p = 0.034). BclI polymorphism was significantly associated with sum of legs FM percentage (β=0.327, p = 0.048). T2DM was negatively associated with BclI polymorphism, after adjusting for age, truncal FM, ALMI, and sum of legs FM (OR=0.158, 95%CI 0.031–0.806, p = 0.027). Conclusions BclI polymorphism is associated with tissue-specific glucocorticoid sensitivity, relative glucocorticoid resistance of the HPA axis and peripheral adipose tissue, and glucocorticoid hypersensitivity at the muscle level. By modulating glucocorticoid and insulin sensitivity, BclI polymorphism appears to reduce the risk of T2DM in women with AIs. |
| Databáze: | OpenAIRE |
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