Dataset Information

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

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.

SUBMITTER: Reimondo G

PROVIDER: S-EPMC5029814 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

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

Reimondo Giuseppe G Chiodini Iacopo I Puglisi Soraya S Pia Anna A Morelli Valentina V Kastelan Darko D Cannavo Salvatore S Berchialla Paola P Giachino Daniela D Perotti Paola P Cuccurullo Alessandra A Paccotti Piero P Beck-Peccoz Paolo P De Marchi Mario M Terzolo Massimo M

PloS one 20160920 9

<h4>Context</h4>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.<h4>Objective</h4>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 ...[more]

PMID: 27649075

Similar Datasets

Project description:BACKGROUND: Since both excess glucocorticoid secretion and central obesity are clinical features of some obese patients, it is worthwhile to study a possible association of glucocorticoid receptor gene (GRL) variants with obesity. Previous studies have linked the N363S variant of the GRL gene to increased glucocorticoid effects such as higher body fat, a lower lean-body mass and a larger insulin response to dexamethasone. However, contradictory findings have been also reported about the association between this variant and obesity phenotypes. Individual studies may lack statistical power which may result in disparate results. This limitation can be overcome using meta-analytic techniques. METHODS: We conducted a meta-analysis to assess the association between the N363S polymorphism of the GRL gene and obesity risk. In addition to published research, we included also our own unpublished data -three novel case-control studies- in the meta-analysis The new case-control studies were conducted in German and Spanish children, adolescents and adults (total number of subjects: 1,117). Genotype was assessed by PCR-RFLP (Tsp509I). The final formal meta-analysis included a total number of 5,909 individuals. RESULTS: The meta-analysis revealed a higher body mass index (BMI) with an overall estimation of +0.18 kg/m2 (95% CI: +0.004 to +0.35) for homo-/heterozygous carriers of the 363S allele of the GRL gene in comparison to non-carriers. Moreover, differences in pooled BMI were statistically significant and positive when considering one-group studies from the literature in which participants had a BMI below 27 kg/m2 (+ 0.41 kg/m2 [95% CI +0.17 to +0.66]), but the differences in BMI were negative when only our novel data from younger (aged under 45) and normal weight subjects were pooled together (-0.50 kg/m2 [95% CI -0.84 to -0.17]). The overall risk for obesity for homo-/heterozygous carriers of the 363S allele was not statistically significant in the meta-analysis (pooled OR = 1.02; 95% CI: 0.56-1.87). CONCLUSION: Although certain genotypic effects could be population-specific, we conclude that there is no compelling evidence that the N363S polymorphism of the GRL gene is associated with either average BMI or obesity risk.

Project description:OBJECTIVE:To determine all-cause mortality risk in patients with and without adrenal incidentaloma. METHODS:Retrospective cohort study of patients with CT abdomen performed within 24 h of emergency room presentation at an academic medical center from January 1, 2005, to December 31, 2009, without history of adrenal disease, adrenal lab testing, or cancer. Incidentaloma cohort identified by database query of imaging reports followed by manual review and matched to no-nodule controls at 3:1 on age?±?1 year and exam date ±?3 months. Mortality ascertained by in-hospital deaths and National Death Index query. Survival analysis performed with Kaplan-Meier curves and Cox proportional hazards models. RESULTS:Among 42,575 adults with abdominal CT exams, 969 adrenal incidentaloma patients and 2907 no-nodule controls were identified. All 3876 individuals entered survival analysis with 31,182 person-years at risk (median follow-up 8.9 years [IQR, 6.9-10.7]). All-cause mortality was significantly higher among those with adrenal incidentalomas (353/969, 36.4%) compared with those without (919/2907, 31.6%; mortality difference 7.6 per 1000 person-years; multivariable-adjusted hazard ratio [aHR] 1.14; 95% CI, 1.003-1.29). Exploratory analyses, limited by missing covariates, found that adrenal incidentalomas were associated with significantly increased incidence of malignancy (aHR 1.61; 95% CI, 1.22-2.12), diabetes (aHR 1.43; 95% CI, 1.18-1.71), heart failure (aHR 1.32; 95% CI, 1.07-1.63), peripheral vascular disease (aHR 1.28; 95% CI, 1.95-1.56), renal disease (aHR 1.21; 95% CI, 1.01-1.44), and chronic pulmonary disease (aHR 1.22; 95% CI, 1.01-1.46) compared with controls. CONCLUSIONS:Adrenal incidentalomas are associated with increased mortality and may represent a clinically valuable biomarker. KEY POINTS:• Adrenal incidentalomas are associated with increased mortality. • Adrenal incidentaloma size is not predictive of mortality. • On exploratory analyses, adrenal incidentalomas are associated with chronic illnesses.

Dataset Information

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

Context

Objective

Setting

Patients

Main outcomes measures

Results

Conclusions

Publications

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

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure