Impact of glucocorticoid receptor gene polymorphisms on the metabolic profile of adult patients with the classical form of 21-hydroxylase deficiency.

<h4>Background</h4>CAH patients have an increased risk of cardiovascular disease, and it remains unknown if lifelong glucocorticoid (GC) treatment is a contributing factor. In the general population, glucocorticoid receptor gene (NR3C1) polymorphisms are associated with an adverse metabo...

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Autores principales:	Ricardo P P Moreira, Larissa G Gomes, Berenice B Mendonca, Tânia A S S Bachega
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2012
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/b170195ebcd84d39a967608b00ea79eb
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spelling	oai:doaj.org-article:b170195ebcd84d39a967608b00ea79eb2021-11-18T07:05:15ZImpact of glucocorticoid receptor gene polymorphisms on the metabolic profile of adult patients with the classical form of 21-hydroxylase deficiency.1932-620310.1371/journal.pone.0044893https://doaj.org/article/b170195ebcd84d39a967608b00ea79eb2012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23028665/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Background</h4>CAH patients have an increased risk of cardiovascular disease, and it remains unknown if lifelong glucocorticoid (GC) treatment is a contributing factor. In the general population, glucocorticoid receptor gene (NR3C1) polymorphisms are associated with an adverse metabolic profile. Our aim was to analyze the association between the NR3C1 polymorphisms and the metabolic profile of CAH patients.<h4>Methodology</h4>Sixty-eight adult patients (34SV/34SW) with a mean age of 28.4±9 years received dexamethasone (mean 0.27±0.11 mg/day) to obtain normal androgen levels. SW patients also received fludrocortisone (50 µg/day). Metabolic syndrome (MetS) was defined by the NCEP ATPIII criteria and obesity by BMI ≥30 kg/m². NR3C1 alleles were genotyped, and association analyses with phenotype were carried out with Chi-square, t-test and regression analysis.<h4>Results</h4>Obesity and MetS were observed in 23.5% and 7.3% of patients, respectively, and were not correlated with GC doses and treatment duration. BMI was positively correlated with blood pressure (BP), triglycerides (TG), LDL-c levels and HOMA-IR and inversely correlated with HDL-c levels. BclI and A3669G variants were found in 26.4% and 9.6% of alleles, respectively. Heterozygotes for the BclI polymorphism presented with higher BMI (29 kg/m²±5.3 vs. 26 kg/m²±5.3, respectively) and waist circumference (89 cm±12.7 vs. 81 cm±13, respectively) compared to wild-type subjects. Hypertension was found in 12% of patients and heterozygotes for the BclI polymorphism presented higher systolic BP than wild type subjects. Low HDL-c and high TG levels were identified in 30% and 10% of patients, respectively, and were not associated with the NR3C1 polymorphisms. A3669G carriers and non-carriers did not differ.<h4>Conclusion</h4>In addition to GC therapy, the BclI GR variant might play an important role in obesity susceptibility in CAH patients. Genotyping of GR polymorphisms could result in the identification of a subgroup at risk patients, allowing for the establishment of personalized treatment and the avoidance of long-term adverse consequences.Ricardo P P MoreiraLarissa G GomesBerenice B MendoncaTânia A S S BachegaPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 7, Iss 9, p e44893 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Ricardo P P Moreira Larissa G Gomes Berenice B Mendonca Tânia A S S Bachega Impact of glucocorticoid receptor gene polymorphisms on the metabolic profile of adult patients with the classical form of 21-hydroxylase deficiency.
description	<h4>Background</h4>CAH patients have an increased risk of cardiovascular disease, and it remains unknown if lifelong glucocorticoid (GC) treatment is a contributing factor. In the general population, glucocorticoid receptor gene (NR3C1) polymorphisms are associated with an adverse metabolic profile. Our aim was to analyze the association between the NR3C1 polymorphisms and the metabolic profile of CAH patients.<h4>Methodology</h4>Sixty-eight adult patients (34SV/34SW) with a mean age of 28.4±9 years received dexamethasone (mean 0.27±0.11 mg/day) to obtain normal androgen levels. SW patients also received fludrocortisone (50 µg/day). Metabolic syndrome (MetS) was defined by the NCEP ATPIII criteria and obesity by BMI ≥30 kg/m². NR3C1 alleles were genotyped, and association analyses with phenotype were carried out with Chi-square, t-test and regression analysis.<h4>Results</h4>Obesity and MetS were observed in 23.5% and 7.3% of patients, respectively, and were not correlated with GC doses and treatment duration. BMI was positively correlated with blood pressure (BP), triglycerides (TG), LDL-c levels and HOMA-IR and inversely correlated with HDL-c levels. BclI and A3669G variants were found in 26.4% and 9.6% of alleles, respectively. Heterozygotes for the BclI polymorphism presented with higher BMI (29 kg/m²±5.3 vs. 26 kg/m²±5.3, respectively) and waist circumference (89 cm±12.7 vs. 81 cm±13, respectively) compared to wild-type subjects. Hypertension was found in 12% of patients and heterozygotes for the BclI polymorphism presented higher systolic BP than wild type subjects. Low HDL-c and high TG levels were identified in 30% and 10% of patients, respectively, and were not associated with the NR3C1 polymorphisms. A3669G carriers and non-carriers did not differ.<h4>Conclusion</h4>In addition to GC therapy, the BclI GR variant might play an important role in obesity susceptibility in CAH patients. Genotyping of GR polymorphisms could result in the identification of a subgroup at risk patients, allowing for the establishment of personalized treatment and the avoidance of long-term adverse consequences.
format	article
author	Ricardo P P Moreira Larissa G Gomes Berenice B Mendonca Tânia A S S Bachega
author_facet	Ricardo P P Moreira Larissa G Gomes Berenice B Mendonca Tânia A S S Bachega
author_sort	Ricardo P P Moreira
title	Impact of glucocorticoid receptor gene polymorphisms on the metabolic profile of adult patients with the classical form of 21-hydroxylase deficiency.
title_short	Impact of glucocorticoid receptor gene polymorphisms on the metabolic profile of adult patients with the classical form of 21-hydroxylase deficiency.
title_full	Impact of glucocorticoid receptor gene polymorphisms on the metabolic profile of adult patients with the classical form of 21-hydroxylase deficiency.
title_fullStr	Impact of glucocorticoid receptor gene polymorphisms on the metabolic profile of adult patients with the classical form of 21-hydroxylase deficiency.
title_full_unstemmed	Impact of glucocorticoid receptor gene polymorphisms on the metabolic profile of adult patients with the classical form of 21-hydroxylase deficiency.
title_sort	impact of glucocorticoid receptor gene polymorphisms on the metabolic profile of adult patients with the classical form of 21-hydroxylase deficiency.
publisher	Public Library of Science (PLoS)
publishDate	2012
url	https://doaj.org/article/b170195ebcd84d39a967608b00ea79eb
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Impact of glucocorticoid receptor gene polymorphisms on the metabolic profile of adult patients with the classical form of 21-hydroxylase deficiency.

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