Analysis of BclI, N363S and ER22/23EK polymorphisms of the glucocorticoid receptor gene in adrenal incidentalomas

Reimondo, Giuseppe and Chiodini, Iacopo and Puglisi, Soraya and Pia, Anna and Morelli, Valentina and Kaštelan, Darko and Cannavo, Salvatore and Berchialla, Paola and Giachino, Daniela and Perotti, Paola and Cuccurullo, Alessandra and Paccotti, Piero and Beck-Peccoz, Paolo and De Marchi, Mario and Terzolo, Massimo (2016) Analysis of BclI, N363S and ER22/23EK polymorphisms of the glucocorticoid receptor gene in adrenal incidentalomas. PLoS ONE, 11 (9). e0162437. ISSN 1932-6203

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Official URL: http://doi.org/10.1371/journal.pone.0162437

Abstract

CONTEXT: Patients with adrenal incidentalomas (AI) may experience detrimental consequences due to a minimal cortisol excess sustained by adrenal adenoma. SNPs of the glucocorticoid receptor gene (NR3C1) modulate individual sensitivity to glucocorticoids and may interfere with the clinical presentation. ----- OBJECTIVE: To compare the frequency of N363S, ER22/23EK and BclI SNPs in patients with AI with the general population and to evaluate whether these SNPs are linked to consequences of cortisol excess. ----- SETTING: Multicentric, retrospective analysis of patients referred from 2010 to 2014 to 4 centers (Orbassano, Milano, Messina [Italy] and Zagreb [Croatia]). ----- PATIENTS: 411 patients with AI; 153 males and 258 females and 186 from blood donors. ----- MAIN OUTCOMES MEASURES: All patients and controls were genotyped for BclI, N363S and ER22/23EK and SNPs frequency was associated with clinical and hormonal features. ----- RESULTS: SNP frequency was: SNP frequency was: N363S 5.4% (MAF 0.027), BclI 54.7% (MAF 0.328), ER22/23EK 4.4% (MAF 0.022), without any significant difference between patients and controls. N363S was more frequent in hypertensive patients (p = 0.03) and was associated with hypertension (p = 0.015) in patients with suppressed cortisol after the 1-mg DST. ----- CONCLUSIONS: Our results demonstrate that SNPs of the glucocorticoid receptor gene do not play a pathogenetic role for AI. The impact of any single SNP on the phenotypic expression of minimal cortisol excess is limited and their analysis does not provide additional data that may be exploited for patient management.

Item Type:

Article

Additional Information:

© 2016 Reimondo et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

MeSH:

Adrenal Gland Neoplasms/blood ; Adrenal Gland Neoplasms/complications ; Adrenal Gland Neoplasms/genetics ; Adrenal Glands/metabolism ; Adrenal Glands/pathology ; Adult ; Aged ; Aged, 80 and over ; Female ; Humans ; Hydrocortisone/blood ; Hypertension/blood ; Hypertension/complications ; Hypertension/genetics ; Male ; Middle Aged ; Polymorphism, Single Nucleotide ; Receptors, Glucocorticoid/genetics

Departments:

Katedra za internu medicinu

Depositing User:

Martina Žužak

Status:

Published

Creators:

Creators	Email
Reimondo, Giuseppe	UNSPECIFIED
Chiodini, Iacopo	UNSPECIFIED
Puglisi, Soraya	UNSPECIFIED
Pia, Anna	UNSPECIFIED
Morelli, Valentina	UNSPECIFIED
Kaštelan, Darko	UNSPECIFIED
Cannavo, Salvatore	UNSPECIFIED
Berchialla, Paola	UNSPECIFIED
Giachino, Daniela	UNSPECIFIED
Perotti, Paola	UNSPECIFIED
Cuccurullo, Alessandra	UNSPECIFIED
Paccotti, Piero	UNSPECIFIED
Beck-Peccoz, Paolo	UNSPECIFIED
De Marchi, Mario	UNSPECIFIED
Terzolo, Massimo	UNSPECIFIED

Date:

20 September 2016

Date Deposited:

11 Oct 2017 07:47

Last Modified:

13 Aug 2020 07:27

Subjects:

UNSPECIFIED

Related URLs:

Publisher

URI:

http://medlib.mef.hr/id/eprint/2709

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