The protective effect of the ER22/23EK polymorphism against an excessive weight gain during pregnancy

Bertalan, Rita; Patócs, Attila; Boyle, Belema; Rigó, János; Rácz, Kàroly

doi:10.1080/09513590902730762

Cited by 7 publications

(5 citation statements)

References 26 publications

(28 reference statements)

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“…For example, the ER22/23EK (rs6189 and rs6190) polymorphism, which occurs in about 3% of the population, is associated with a more favorable metabolic profile, including a lower risk of both type 2 diabetes and cardiovascular disease [50]. This effect is conferred via reduced glucocorticoid sensitivity, which is mediated by a change from GAG AGG to GAA AAG in exon 2 at position 23 within the NTD [72,73].…”

Section: Gr Polymorphismsmentioning

confidence: 99%

The Glucocorticoid Receptor in Cardiovascular Health and Disease

Liu

Zhang

Knight

et al. 2019

Cells

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The glucocorticoid receptor is a member of the nuclear receptor family that controls many distinct gene networks, governing various aspects of development, metabolism, inflammation, and the stress response, as well as other key biological processes in the cardiovascular system. Recently, research in both animal models and humans has begun to unravel the profound complexity of glucocorticoid signaling and convincingly demonstrates that the glucocorticoid receptor has direct effects on the heart and vessels in vivo and in vitro. This research has contributed directly to improving therapeutic strategies in human disease. The glucocorticoid receptor is activated either by the endogenous steroid hormone cortisol or by exogenous glucocorticoids and acts within the cardiovascular system via both genomic and non-genomic pathways. Polymorphisms of the glucocorticoid receptor are also reported to influence the progress and prognosis of cardiovascular disease. In this review, we provide an update on glucocorticoid signaling and highlight the critical role of this signaling in both physiological and pathological conditions of the cardiovascular system. With increasing in-depth understanding of glucocorticoid signaling, the future is promising for the development of targeted glucocorticoid treatments and improved clinical outcomes.

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Section: Gr Polymorphismsmentioning

confidence: 99%

The Glucocorticoid Receptor in Cardiovascular Health and Disease

Liu

Zhang

Knight

et al. 2019

Cells

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“…The ER22/23EK polymorphism is associated with a healthy metabolic and inflammatory profile, characterized by lower total cholesterol and low-density lipoprotein cholesterol levels as well as lower fasting insulin concentrations, a better insulin sensitivity and lower C-reactive protein levels [31,34]. This GR variant is also associated with a beneficial body composition, shown by young male ER22/23EK carriers (taller, stronger and more muscle mass than noncarriers) and female ER22/23EK carriers (tendencies for smaller waist and hip circumferences, lower body weight [35], and protective effect on weight gain during pregnancy [32,36]). These associations of the ER22/23EK polymorphism are in line with a mild GR resistance.…”

Section: Genetics Of Hpa Axis: Consequences For Physical and Mental Hmentioning

confidence: 99%

Glucocorticoid Sensitivity in Mood Disorders

Spijker

Rossum

2011

Neuroendocrinology

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In this review, we provide an overview of recent literature on glucocorticoid (GC) sensitivity in mood disorders. Assessing GC sensitivity is often performed by measuring the cortisol awakening rise (CAR), by challenging the hypothalamic-pituitary–adrenal (HPA) axis using a dexamethasone suppression test (DST) or a dexamethasone/cortisol-releasing hormone test (DEX/CRH); more recently by measuring cortisol as a retrospective calendar in scalp hair. The main findings in mood disorders are higher mean cortisol levels in hair samples and a higher CAR, showing a hyperactivity of the HPA axis. This is in line with the mild resistance for GCs previously observed in challenge tests during mood episodes. GC sensitivity is partly determined by polymorphisms in the genes encoding receptors and other proteins involved in the regulation of the HPA axis. We shortly discuss the glucocorticoid receptor, as well as the mineralocorticoid receptor, the cortisol-releasing hormone receptor-1, and the glucocorticoid receptor co-chaperone FKBP5. Data clearly indicate genetic changes, along with epigenetic changes which influence the set-point and regulation of the HPA axis. Early trauma, as well as influences in utero, appears to be important. Future research is necessary to further clarify the biological background and consequences of an individual’s cortisol exposure in relation to mood.

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“…Conflicting results have been also reported for the ER22/23EK polymorphism in general population. Some studies demonstrated higher cortisol levels after dexamethasone suppression associated to increased insulin sensitivity, better metabolic profile and reduced weight, although with a striking gender difference in the SNP effect [ 3 , 8 , 33 , 34 ]. Other studies did not confirm these data [ 26 , 35 ].…”

Section: Discussionmentioning

confidence: 99%

Analysis of BCLI, N363S and ER22/23EK Polymorphisms of the Glucocorticoid Receptor Gene in Adrenal Incidentalomas

et al. 2016

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ContextPatients 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.ObjectiveTo 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.SettingMulticentric, retrospective analysis of patients referred from 2010 to 2014 to 4 centers (Orbassano, Milano, Messina [Italy] and Zagreb [Croatia]).Patients411 patients with AI; 153 males and 258 females and 186 from blood donors.Main outcomes measuresAll patients and controls were genotyped for BclI, N363S and ER22/23EK and SNPs frequency was associated with clinical and hormonal features.ResultsSNP 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.ConclusionsOur 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.

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The protective effect of the ER22/23EK polymorphism against an excessive weight gain during pregnancy

Cited by 7 publications

References 26 publications

The Glucocorticoid Receptor in Cardiovascular Health and Disease

The Glucocorticoid Receptor in Cardiovascular Health and Disease

Glucocorticoid Sensitivity in Mood Disorders

Analysis of BCLI, N363S and ER22/23EK Polymorphisms of the Glucocorticoid Receptor Gene in Adrenal Incidentalomas

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