Glucocorticoid Receptor Polymorphisms Influence Muscle Strength in Cushing’s Syndrome
| Autor: | Andrea Oßwald, Leah T. Braun, Tina Kienitz, Christina M. Berr, German Rubinstein, Martin Reincke, Anna Riester, Marcus Quinkler, Lisa Müller, Stephanie Burger-Stritt, Timo Deutschbein, Stefanie Hahner |
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| Rok vydání: | 2019 |
| Předmět: |
Adult
Male medicine.medical_specialty Adolescent Genotype Endocrinology Diabetes and Metabolism Clinical Biochemistry 030209 endocrinology & metabolism Biochemistry Young Adult 03 medical and health sciences Grip strength Receptors Glucocorticoid 0302 clinical medicine Endocrinology Glucocorticoid receptor Glucocorticoid Sensitivity Gene Frequency Muscular Diseases Germany Internal medicine medicine Humans Genetic Predisposition to Disease Muscle Strength Registries 030212 general & internal medicine Myopathy Cushing Syndrome Aged Aged 80 and over Sex Characteristics Polymorphism Genetic Hand Strength business.industry Biochemistry (medical) Wild type Middle Aged Minor allele frequency Cross-Sectional Studies Hypercortisolemia Female medicine.symptom business Glucocorticoid medicine.drug |
| Zdroj: | The Journal of Clinical Endocrinology & Metabolism. 105:305-313 |
| ISSN: | 1945-7197 0021-972X |
| DOI: | 10.1210/clinem/dgz052 |
| Popis: | Context An important clinical feature of Cushing’s syndrome (CS) is proximal muscle myopathy caused by glucocorticoid induced protein metabolism. However, interindividual differences cannot be explained solely by the pure extent of hypercortisolemia. Objective To evaluate the effects of glucocorticoid receptor (GR) polymorphisms (BclI, N363S, ER22/23EK and A3669G), which influence peripheral glucocorticoid sensitivity on muscular function in endogenous CS. Methods 205 patients with proven endogenous CS (128 central, 77 adrenal) from 3 centers of the German Cushing’s Registry and 125 subjects, in whom CS was ruled out, were included. All subjects were assessed for grip strength (via hand grip dynamometer) and performed a chair-rising test (CRT). DNA samples were obtained from peripheral blood leukocytes for GR genotyping. Results In patients with active CS, normalized handgrip strength of the dominant and nondominant hand was higher in A3669G minor allele than in wildtype carriers (P = .006 and P = .021, respectively). CS patients in remission and ruled-out CS showed no differences in handgrip strength regarding A3669G minor allele and wildtype carriers. Male CS patients harboring the ER22/23EK wildtype presented lower hand grip strength than minor allele carriers (P = .049 dominant hand; P = .027 nondominant hand). The other polymorphisms did not influence handgrip strength. CRT showed no differences regarding GR polymorphisms carrier status. Conclusion Handgrip strength seems to be more susceptible to hypercortisolism in A3669G wildtype than in A3669G minor allele carriers. This might partially explain the inter-individual differences of glucocorticoid-induced myopathy in patients with endogenous CS. ER22/23EK polymorphism seems to exert sex-specific differences. |
| Databáze: | OpenAIRE |
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