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Glucocorticoid receptor polymorphisms modulate cardiometabolic risk factors in patients in long-term remission of Cushing’s syndrome

CONTEXT: Glucocorticoid receptor (GR) polymorphisms modulate glucocorticoid (GC) sensitivity and are associated with altered metabolic profiles. OBJECTIVE: To evaluate the presence of GR polymorphisms (BclI (rs41423247), N363S (rs56149945), ER22/23EK (rs6189/rs6190), and 9β (rs6198) and investigate...

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Autores principales: Roerink, Sean H. P. P., Wagenmakers, M. A. E. M., Smit, J. W. A., van Rossum, E. F. C., Netea-Maier, R. T., Plantinga, T. S., Hermus, A. R. M. M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer US 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4901092/
https://www.ncbi.nlm.nih.gov/pubmed/26873309
http://dx.doi.org/10.1007/s12020-016-0883-z
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author Roerink, Sean H. P. P.
Wagenmakers, M. A. E. M.
Smit, J. W. A.
van Rossum, E. F. C.
Netea-Maier, R. T.
Plantinga, T. S.
Hermus, A. R. M. M.
author_facet Roerink, Sean H. P. P.
Wagenmakers, M. A. E. M.
Smit, J. W. A.
van Rossum, E. F. C.
Netea-Maier, R. T.
Plantinga, T. S.
Hermus, A. R. M. M.
author_sort Roerink, Sean H. P. P.
collection PubMed
description CONTEXT: Glucocorticoid receptor (GR) polymorphisms modulate glucocorticoid (GC) sensitivity and are associated with altered metabolic profiles. OBJECTIVE: To evaluate the presence of GR polymorphisms (BclI (rs41423247), N363S (rs56149945), ER22/23EK (rs6189/rs6190), and 9β (rs6198) and investigate their associations with metabolic alterations in patients in long-term remission of Cushing’s syndrome (CS). DESIGN AND SETTING: Cross-sectional case–control study. PATIENTS AND METHODS: Sixty patients in long-term remission of CS were genotyped. Associations between GR polymorphisms and multiple vascular, body composition and metabolic parameters were investigated. MAIN OUTCOME MEASURES: Allelic frequencies of the polymorphisms and their associations with several cardiometabolic risk factors. RESULTS: This study shows that carriers of the 9β polymorphism have a higher systolic blood pressure and lower resistin levels. The GC sensitizing BclI polymorphism is associated with an adverse cardiometabolic risk factor profile: higher fat percentages of extremities and legs, higher serum leptin and E-selectin levels, and higher intima media thickness in carriers versus non-carriers. CONCLUSIONS: The 9β and BclI polymorphisms of the GR adversely affect the cardiometabolic profile in patients who are in remission after the treatment of CS. This suggests that genetically altered GC sensitivity modulates the long-term adverse cardiometabolic effects resulting from (endogenous) hypercortisolism.
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spelling pubmed-49010922016-06-27 Glucocorticoid receptor polymorphisms modulate cardiometabolic risk factors in patients in long-term remission of Cushing’s syndrome Roerink, Sean H. P. P. Wagenmakers, M. A. E. M. Smit, J. W. A. van Rossum, E. F. C. Netea-Maier, R. T. Plantinga, T. S. Hermus, A. R. M. M. Endocrine Endocrine Genetics/Epigenetics CONTEXT: Glucocorticoid receptor (GR) polymorphisms modulate glucocorticoid (GC) sensitivity and are associated with altered metabolic profiles. OBJECTIVE: To evaluate the presence of GR polymorphisms (BclI (rs41423247), N363S (rs56149945), ER22/23EK (rs6189/rs6190), and 9β (rs6198) and investigate their associations with metabolic alterations in patients in long-term remission of Cushing’s syndrome (CS). DESIGN AND SETTING: Cross-sectional case–control study. PATIENTS AND METHODS: Sixty patients in long-term remission of CS were genotyped. Associations between GR polymorphisms and multiple vascular, body composition and metabolic parameters were investigated. MAIN OUTCOME MEASURES: Allelic frequencies of the polymorphisms and their associations with several cardiometabolic risk factors. RESULTS: This study shows that carriers of the 9β polymorphism have a higher systolic blood pressure and lower resistin levels. The GC sensitizing BclI polymorphism is associated with an adverse cardiometabolic risk factor profile: higher fat percentages of extremities and legs, higher serum leptin and E-selectin levels, and higher intima media thickness in carriers versus non-carriers. CONCLUSIONS: The 9β and BclI polymorphisms of the GR adversely affect the cardiometabolic profile in patients who are in remission after the treatment of CS. This suggests that genetically altered GC sensitivity modulates the long-term adverse cardiometabolic effects resulting from (endogenous) hypercortisolism. Springer US 2016-02-13 2016 /pmc/articles/PMC4901092/ /pubmed/26873309 http://dx.doi.org/10.1007/s12020-016-0883-z Text en © The Author(s) 2016 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.
spellingShingle Endocrine Genetics/Epigenetics
Roerink, Sean H. P. P.
Wagenmakers, M. A. E. M.
Smit, J. W. A.
van Rossum, E. F. C.
Netea-Maier, R. T.
Plantinga, T. S.
Hermus, A. R. M. M.
Glucocorticoid receptor polymorphisms modulate cardiometabolic risk factors in patients in long-term remission of Cushing’s syndrome
title Glucocorticoid receptor polymorphisms modulate cardiometabolic risk factors in patients in long-term remission of Cushing’s syndrome
title_full Glucocorticoid receptor polymorphisms modulate cardiometabolic risk factors in patients in long-term remission of Cushing’s syndrome
title_fullStr Glucocorticoid receptor polymorphisms modulate cardiometabolic risk factors in patients in long-term remission of Cushing’s syndrome
title_full_unstemmed Glucocorticoid receptor polymorphisms modulate cardiometabolic risk factors in patients in long-term remission of Cushing’s syndrome
title_short Glucocorticoid receptor polymorphisms modulate cardiometabolic risk factors in patients in long-term remission of Cushing’s syndrome
title_sort glucocorticoid receptor polymorphisms modulate cardiometabolic risk factors in patients in long-term remission of cushing’s syndrome
topic Endocrine Genetics/Epigenetics
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4901092/
https://www.ncbi.nlm.nih.gov/pubmed/26873309
http://dx.doi.org/10.1007/s12020-016-0883-z
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