Modulatory effect of BclI GR gene polymorphisms on the obesity phenotype in Brazilian patients with Cushing's disease
Autor(a) principal: | |
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Data de Publicação: | 2013 |
Outros Autores: | , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Clinics |
Texto Completo: | https://www.revistas.usp.br/clinics/article/view/76831 |
Resumo: | OBJECTIVES: Patients with Cushing's disease exhibit wide phenotypic variability in the severity of obesity, diabetes and hypertension. In the general population, several glucocorticoid receptor genes (NR3C1) and HSD11B1 polymorphisms are associated with altered glucocorticoid sensitivity and/or metabolism, resulting in an increased or reduced risk of an adverse metabolic profile. Our aim was to analyze the association of NR3C1 and HSD11B1 gene variants with the severity of some clinical and hormonal features of Cushing's disease. METHODS: Sixty-four patients presenting with Cushing's disease were diagnosed based on adrenocorticotrophic hormone levels, high-dose dexamethasone suppression tests and/or inferior petrosal sinus sampling and magnetic resonance imaging. The A3669G, ER22/23EK, N363S BclI-NR3C1 and HSD11B1-rs12086634 variants were screened. RESULTS: The BclI, HSD11B1-rs12086634 and A3669G variants were found in 36%, 19.5% and 14% of alleles, respectively. The N363S and ER22/23EK polymorphisms were identified in heterozygosis once in only two patients (1.5% of alleles). There were no differences in the weight gain or prevalence of diabetes and hypertension in the patients carrying the abovementioned alleles compared to the wild-type carriers. Interestingly, the mean body mass index (BMI) of the BclI carriers was significantly higher than the non-carriers (34.4±7 kg/m2 vs. 29.6±4.7 kg/m2, respectively). None of the polymorphisms were associated with the basal adrenocorticotrophic hormone, FU levels or F level after dexamethasone suppression testing. CONCLUSION: Although Cushing's disease results from increased glucocorticoid secretion, we observed that interindividual variability in the peripheral glucocorticoid sensitivity, mediated by the glucocorticoid receptor, could modulate the obesity phenotype. |
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oai:revistas.usp.br:article/76831 |
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network_name_str |
Clinics |
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Modulatory effect of BclI GR gene polymorphisms on the obesity phenotype in Brazilian patients with Cushing's diseaseOBJECTIVES: Patients with Cushing's disease exhibit wide phenotypic variability in the severity of obesity, diabetes and hypertension. In the general population, several glucocorticoid receptor genes (NR3C1) and HSD11B1 polymorphisms are associated with altered glucocorticoid sensitivity and/or metabolism, resulting in an increased or reduced risk of an adverse metabolic profile. Our aim was to analyze the association of NR3C1 and HSD11B1 gene variants with the severity of some clinical and hormonal features of Cushing's disease. METHODS: Sixty-four patients presenting with Cushing's disease were diagnosed based on adrenocorticotrophic hormone levels, high-dose dexamethasone suppression tests and/or inferior petrosal sinus sampling and magnetic resonance imaging. The A3669G, ER22/23EK, N363S BclI-NR3C1 and HSD11B1-rs12086634 variants were screened. RESULTS: The BclI, HSD11B1-rs12086634 and A3669G variants were found in 36%, 19.5% and 14% of alleles, respectively. The N363S and ER22/23EK polymorphisms were identified in heterozygosis once in only two patients (1.5% of alleles). There were no differences in the weight gain or prevalence of diabetes and hypertension in the patients carrying the abovementioned alleles compared to the wild-type carriers. Interestingly, the mean body mass index (BMI) of the BclI carriers was significantly higher than the non-carriers (34.4±7 kg/m2 vs. 29.6±4.7 kg/m2, respectively). None of the polymorphisms were associated with the basal adrenocorticotrophic hormone, FU levels or F level after dexamethasone suppression testing. CONCLUSION: Although Cushing's disease results from increased glucocorticoid secretion, we observed that interindividual variability in the peripheral glucocorticoid sensitivity, mediated by the glucocorticoid receptor, could modulate the obesity phenotype.Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo2013-05-01info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfhttps://www.revistas.usp.br/clinics/article/view/7683110.1590/clin.v68i5.76831Clinics; Vol. 68 No. 5 (2013); 579-585Clinics; v. 68 n. 5 (2013); 579-585Clinics; Vol. 68 Núm. 5 (2013); 579-5851980-53221807-5932reponame:Clinicsinstname:Universidade de São Paulo (USP)instacron:USPenghttps://www.revistas.usp.br/clinics/article/view/76831/80693Moreira, Ricardo P.P.Bachega, Tânia A.S.S.Machado, Márcio C.Mendonca, Berenice B.Bronstein, Marcello D.Villares Fragoso, Maria Candida B.info:eu-repo/semantics/openAccess2014-03-21T19:31:25Zoai:revistas.usp.br:article/76831Revistahttps://www.revistas.usp.br/clinicsPUBhttps://www.revistas.usp.br/clinics/oai||clinics@hc.fm.usp.br1980-53221807-5932opendoar:2014-03-21T19:31:25Clinics - Universidade de São Paulo (USP)false |
dc.title.none.fl_str_mv |
Modulatory effect of BclI GR gene polymorphisms on the obesity phenotype in Brazilian patients with Cushing's disease |
title |
Modulatory effect of BclI GR gene polymorphisms on the obesity phenotype in Brazilian patients with Cushing's disease |
spellingShingle |
Modulatory effect of BclI GR gene polymorphisms on the obesity phenotype in Brazilian patients with Cushing's disease Moreira, Ricardo P.P. |
title_short |
Modulatory effect of BclI GR gene polymorphisms on the obesity phenotype in Brazilian patients with Cushing's disease |
title_full |
Modulatory effect of BclI GR gene polymorphisms on the obesity phenotype in Brazilian patients with Cushing's disease |
title_fullStr |
Modulatory effect of BclI GR gene polymorphisms on the obesity phenotype in Brazilian patients with Cushing's disease |
title_full_unstemmed |
Modulatory effect of BclI GR gene polymorphisms on the obesity phenotype in Brazilian patients with Cushing's disease |
title_sort |
Modulatory effect of BclI GR gene polymorphisms on the obesity phenotype in Brazilian patients with Cushing's disease |
author |
Moreira, Ricardo P.P. |
author_facet |
Moreira, Ricardo P.P. Bachega, Tânia A.S.S. Machado, Márcio C. Mendonca, Berenice B. Bronstein, Marcello D. Villares Fragoso, Maria Candida B. |
author_role |
author |
author2 |
Bachega, Tânia A.S.S. Machado, Márcio C. Mendonca, Berenice B. Bronstein, Marcello D. Villares Fragoso, Maria Candida B. |
author2_role |
author author author author author |
dc.contributor.author.fl_str_mv |
Moreira, Ricardo P.P. Bachega, Tânia A.S.S. Machado, Márcio C. Mendonca, Berenice B. Bronstein, Marcello D. Villares Fragoso, Maria Candida B. |
description |
OBJECTIVES: Patients with Cushing's disease exhibit wide phenotypic variability in the severity of obesity, diabetes and hypertension. In the general population, several glucocorticoid receptor genes (NR3C1) and HSD11B1 polymorphisms are associated with altered glucocorticoid sensitivity and/or metabolism, resulting in an increased or reduced risk of an adverse metabolic profile. Our aim was to analyze the association of NR3C1 and HSD11B1 gene variants with the severity of some clinical and hormonal features of Cushing's disease. METHODS: Sixty-four patients presenting with Cushing's disease were diagnosed based on adrenocorticotrophic hormone levels, high-dose dexamethasone suppression tests and/or inferior petrosal sinus sampling and magnetic resonance imaging. The A3669G, ER22/23EK, N363S BclI-NR3C1 and HSD11B1-rs12086634 variants were screened. RESULTS: The BclI, HSD11B1-rs12086634 and A3669G variants were found in 36%, 19.5% and 14% of alleles, respectively. The N363S and ER22/23EK polymorphisms were identified in heterozygosis once in only two patients (1.5% of alleles). There were no differences in the weight gain or prevalence of diabetes and hypertension in the patients carrying the abovementioned alleles compared to the wild-type carriers. Interestingly, the mean body mass index (BMI) of the BclI carriers was significantly higher than the non-carriers (34.4±7 kg/m2 vs. 29.6±4.7 kg/m2, respectively). None of the polymorphisms were associated with the basal adrenocorticotrophic hormone, FU levels or F level after dexamethasone suppression testing. CONCLUSION: Although Cushing's disease results from increased glucocorticoid secretion, we observed that interindividual variability in the peripheral glucocorticoid sensitivity, mediated by the glucocorticoid receptor, could modulate the obesity phenotype. |
publishDate |
2013 |
dc.date.none.fl_str_mv |
2013-05-01 |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
https://www.revistas.usp.br/clinics/article/view/76831 10.1590/clin.v68i5.76831 |
url |
https://www.revistas.usp.br/clinics/article/view/76831 |
identifier_str_mv |
10.1590/clin.v68i5.76831 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
https://www.revistas.usp.br/clinics/article/view/76831/80693 |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
application/pdf |
dc.publisher.none.fl_str_mv |
Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo |
publisher.none.fl_str_mv |
Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo |
dc.source.none.fl_str_mv |
Clinics; Vol. 68 No. 5 (2013); 579-585 Clinics; v. 68 n. 5 (2013); 579-585 Clinics; Vol. 68 Núm. 5 (2013); 579-585 1980-5322 1807-5932 reponame:Clinics instname:Universidade de São Paulo (USP) instacron:USP |
instname_str |
Universidade de São Paulo (USP) |
instacron_str |
USP |
institution |
USP |
reponame_str |
Clinics |
collection |
Clinics |
repository.name.fl_str_mv |
Clinics - Universidade de São Paulo (USP) |
repository.mail.fl_str_mv |
||clinics@hc.fm.usp.br |
_version_ |
1800222760138440704 |