Reimondo Giuseppe, Chiodini Iacopo, Puglisi Soraya, Pia Anna, Morelli Valentina, Kastelan Darko, Cannavo Salvatore, Berchialla Paola, Giachino Daniela, Perotti Paola, Cuccurullo Alessandra, Paccotti Piero, Beck-Peccoz Paolo, De Marchi Mario, Terzolo Massimo
Internal Medicine 1, Department of Clinical and Biological Sciences, University of Turin, San Luigi Gonzaga Hospital, Orbassano, Italy.
Unit of Endocrinology and Metabolic Diseases, Fondazione IRCCS Cà Granda-Ospedale Maggiore Policlinico, Milano Department of Clinical Sciences and Community Health, University of Milan, Milan, Italy.
PLoS One. 2016 Sep 20;11(9):e0162437. doi: 10.1371/journal.pone.0162437. eCollection 2016.
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.
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.
Multicentric, retrospective analysis of patients referred from 2010 to 2014 to 4 centers (Orbassano, Milano, Messina [Italy] and Zagreb [Croatia]).
411 patients with AI; 153 males and 258 females and 186 from blood donors.
All patients and controls were genotyped for BclI, N363S and ER22/23EK and SNPs frequency was associated with clinical and hormonal features.
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.
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.
肾上腺偶发瘤（AI）患者可能因肾上腺腺瘤维持的轻度皮质醇过量而出现不良后果。糖皮质激素受体基因（NR3C1）的单核苷酸多态性（SNP）调节个体对糖皮质激素的敏感性，并可能干扰临床表现。
比较AI患者与普通人群中N363S、ER22/23EK和BclI SNP的频率，并评估这些SNP是否与皮质醇过量的后果相关。
对2010年至2014年转诊至4个中心（意大利奥尔巴萨诺、米兰、墨西拿和克罗地亚萨格勒布）的患者进行多中心回顾性分析。
AI患者411例，男性153例，女性258例，以及186名献血者。
对所有患者和对照进行BclI、N363S和ER22/23EK基因分型，并将SNP频率与临床和激素特征相关联。
SNP频率分别为：N363S 5.4%（最小等位基因频率[MAF] 0.027），BclI 54.7%（MAF 0.328），ER22/23EK 4.4%（MAF 0.022），患者与对照之间无显著差异。N363S在高血压患者中更常见（p = 0.03），并且与1毫克地塞米松抑制试验（DST）后皮质醇被抑制的患者的高血压相关（p = 0.015）。
我们的结果表明，糖皮质激素受体基因的SNP对AI不发挥致病作用。任何单个SNP对轻度皮质醇过量表型表达的影响有限，其分析不能提供可用于患者管理的额外数据。
