SAT-310 Analysis of the Influence of Glucocorticoid Receptor Gene Polymorphism BCL-1 on Clinical and Psychiatric Manifestations in Brazilian Patients with Cushing’s Disease
In Cushing’s disease (CD), the spectrum of clinical manifestations is considerably wide, and the intensity of symptoms does not correlate with the magnitude of cortisol hypersecretion or with pituitary tumor size. Polymorphisms in the gene that encodes the glucocorticoid receptor (GR), an essential...
Autores principales: | , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Oxford University Press
2020
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7209618/ http://dx.doi.org/10.1210/jendso/bvaa046.1966 |
_version_ | 1783531120239837184 |
---|---|
author | Garcia, Erica Amato, Angelica Amorim Barra, Gustavo Barcelos Naves, Luciana Ansaneli Vilar, Lucio Neves, Francisco de Assis Rocha Azevedo, Monalisa Ferreira |
author_facet | Garcia, Erica Amato, Angelica Amorim Barra, Gustavo Barcelos Naves, Luciana Ansaneli Vilar, Lucio Neves, Francisco de Assis Rocha Azevedo, Monalisa Ferreira |
author_sort | Garcia, Erica |
collection | PubMed |
description | In Cushing’s disease (CD), the spectrum of clinical manifestations is considerably wide, and the intensity of symptoms does not correlate with the magnitude of cortisol hypersecretion or with pituitary tumor size. Polymorphisms in the gene that encodes the glucocorticoid receptor (GR), an essential regulator of the hypothalamic-pituitary-adrenal axis, have been linked to some psychiatric disorders. Considering that psychiatric manifestations are present in nearly all patients with hypercortisolism, we hypothesized a possible correlation of polymorphisms in the GR gene and clinical and psychiatric manifestations, in CD. To investigate the frequency and clinical implications of the GR gene polymorphism Bcl-1 in patients with CD, we conducted a cross-sectional, case-controlled study. Fifty-three Brazilian patients with CD aged between 12 and 75 years and one hundred healthy controls aged between 42 and 67 years, of both genders, who provided written informed consent, were enrolled. Blood samples were collected from patients for DNA extraction and sequencing for analysis of the GR gene polymorphism Bcl-1. Clinical data (obesity, skin lesions, muscle weakness, hypertension, diabetes, hypokalemia, and sex-related disorders) were obtained through retrospective analysis of medical records, appointment with endocrinologist and with psychiatrist. Mini International Neuropsychiatric Interview, scales self-applicable of anxiety and depression were used to address psychiatric conditions. From the 53 patients studied, 48 were women (90,56%), and 16 patients had macroadenoma (2 of them had tumors larger than 4 cm). Overall frequencies of the Minor Allele for Bcl-1 polymorphism, which corresponds to the risk allele for psychiatric illness in the normal population, did not significantly differ between CD patients (67.92%) and controls (74.00%). Similarly, differences in Minor Allele Frequencies among subgroups of patients presenting with psychiatric and clinical manifestations of CD were not statistically significant. Although data from the literature strongly suggests a correlation between Bcl-1 polymorphism with psychiatric disorders (especially depression) in the normal population, this association was not observed in our cohort of patients with CD. More studies are needed to better clarify a possible role for GR gene polymorphisms as modifiers of the spectrum of psychiatric and clinical manifestations of CD. |
format | Online Article Text |
id | pubmed-7209618 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Oxford University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-72096182020-05-13 SAT-310 Analysis of the Influence of Glucocorticoid Receptor Gene Polymorphism BCL-1 on Clinical and Psychiatric Manifestations in Brazilian Patients with Cushing’s Disease Garcia, Erica Amato, Angelica Amorim Barra, Gustavo Barcelos Naves, Luciana Ansaneli Vilar, Lucio Neves, Francisco de Assis Rocha Azevedo, Monalisa Ferreira J Endocr Soc Neuroendocrinology and Pituitary In Cushing’s disease (CD), the spectrum of clinical manifestations is considerably wide, and the intensity of symptoms does not correlate with the magnitude of cortisol hypersecretion or with pituitary tumor size. Polymorphisms in the gene that encodes the glucocorticoid receptor (GR), an essential regulator of the hypothalamic-pituitary-adrenal axis, have been linked to some psychiatric disorders. Considering that psychiatric manifestations are present in nearly all patients with hypercortisolism, we hypothesized a possible correlation of polymorphisms in the GR gene and clinical and psychiatric manifestations, in CD. To investigate the frequency and clinical implications of the GR gene polymorphism Bcl-1 in patients with CD, we conducted a cross-sectional, case-controlled study. Fifty-three Brazilian patients with CD aged between 12 and 75 years and one hundred healthy controls aged between 42 and 67 years, of both genders, who provided written informed consent, were enrolled. Blood samples were collected from patients for DNA extraction and sequencing for analysis of the GR gene polymorphism Bcl-1. Clinical data (obesity, skin lesions, muscle weakness, hypertension, diabetes, hypokalemia, and sex-related disorders) were obtained through retrospective analysis of medical records, appointment with endocrinologist and with psychiatrist. Mini International Neuropsychiatric Interview, scales self-applicable of anxiety and depression were used to address psychiatric conditions. From the 53 patients studied, 48 were women (90,56%), and 16 patients had macroadenoma (2 of them had tumors larger than 4 cm). Overall frequencies of the Minor Allele for Bcl-1 polymorphism, which corresponds to the risk allele for psychiatric illness in the normal population, did not significantly differ between CD patients (67.92%) and controls (74.00%). Similarly, differences in Minor Allele Frequencies among subgroups of patients presenting with psychiatric and clinical manifestations of CD were not statistically significant. Although data from the literature strongly suggests a correlation between Bcl-1 polymorphism with psychiatric disorders (especially depression) in the normal population, this association was not observed in our cohort of patients with CD. More studies are needed to better clarify a possible role for GR gene polymorphisms as modifiers of the spectrum of psychiatric and clinical manifestations of CD. Oxford University Press 2020-05-08 /pmc/articles/PMC7209618/ http://dx.doi.org/10.1210/jendso/bvaa046.1966 Text en © Endocrine Society 2020. http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs licence (http://creativecommons.org/licenses/by-nc-nd/4.0/), which permits non-commercial reproduction and distribution of the work, in any medium, provided the original work is not altered or transformed in any way, and that the work is properly cited. For commercial re-use, please contact journals.permissions@oup.com |
spellingShingle | Neuroendocrinology and Pituitary Garcia, Erica Amato, Angelica Amorim Barra, Gustavo Barcelos Naves, Luciana Ansaneli Vilar, Lucio Neves, Francisco de Assis Rocha Azevedo, Monalisa Ferreira SAT-310 Analysis of the Influence of Glucocorticoid Receptor Gene Polymorphism BCL-1 on Clinical and Psychiatric Manifestations in Brazilian Patients with Cushing’s Disease |
title | SAT-310 Analysis of the Influence of Glucocorticoid Receptor Gene Polymorphism BCL-1 on Clinical and Psychiatric Manifestations in Brazilian Patients with Cushing’s Disease |
title_full | SAT-310 Analysis of the Influence of Glucocorticoid Receptor Gene Polymorphism BCL-1 on Clinical and Psychiatric Manifestations in Brazilian Patients with Cushing’s Disease |
title_fullStr | SAT-310 Analysis of the Influence of Glucocorticoid Receptor Gene Polymorphism BCL-1 on Clinical and Psychiatric Manifestations in Brazilian Patients with Cushing’s Disease |
title_full_unstemmed | SAT-310 Analysis of the Influence of Glucocorticoid Receptor Gene Polymorphism BCL-1 on Clinical and Psychiatric Manifestations in Brazilian Patients with Cushing’s Disease |
title_short | SAT-310 Analysis of the Influence of Glucocorticoid Receptor Gene Polymorphism BCL-1 on Clinical and Psychiatric Manifestations in Brazilian Patients with Cushing’s Disease |
title_sort | sat-310 analysis of the influence of glucocorticoid receptor gene polymorphism bcl-1 on clinical and psychiatric manifestations in brazilian patients with cushing’s disease |
topic | Neuroendocrinology and Pituitary |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7209618/ http://dx.doi.org/10.1210/jendso/bvaa046.1966 |
work_keys_str_mv | AT garciaerica sat310analysisoftheinfluenceofglucocorticoidreceptorgenepolymorphismbcl1onclinicalandpsychiatricmanifestationsinbrazilianpatientswithcushingsdisease AT amatoangelicaamorim sat310analysisoftheinfluenceofglucocorticoidreceptorgenepolymorphismbcl1onclinicalandpsychiatricmanifestationsinbrazilianpatientswithcushingsdisease AT barragustavobarcelos sat310analysisoftheinfluenceofglucocorticoidreceptorgenepolymorphismbcl1onclinicalandpsychiatricmanifestationsinbrazilianpatientswithcushingsdisease AT naveslucianaansaneli sat310analysisoftheinfluenceofglucocorticoidreceptorgenepolymorphismbcl1onclinicalandpsychiatricmanifestationsinbrazilianpatientswithcushingsdisease AT vilarlucio sat310analysisoftheinfluenceofglucocorticoidreceptorgenepolymorphismbcl1onclinicalandpsychiatricmanifestationsinbrazilianpatientswithcushingsdisease AT nevesfranciscodeassisrocha sat310analysisoftheinfluenceofglucocorticoidreceptorgenepolymorphismbcl1onclinicalandpsychiatricmanifestationsinbrazilianpatientswithcushingsdisease AT azevedomonalisaferreira sat310analysisoftheinfluenceofglucocorticoidreceptorgenepolymorphismbcl1onclinicalandpsychiatricmanifestationsinbrazilianpatientswithcushingsdisease |