Majnik Judit, Patocs Attila, Balogh Katalin, Toth Miklos, Gergics Peter, Szappanos Agnes, Mondok Agnes, Borgulya Gabor, Panczel Pal, Prohaszka Zoltan, Racz Karoly
2nd Department of Medicine, Semmelweis University, Szentkiralyi 46, H-1088 Budapest, Hungary.
J Clin Endocrinol Metab. 2006 Jul;91(7):2796-9. doi: 10.1210/jc.2006-0066. Epub 2006 Apr 24.
Some variants of the glucocorticoid receptor (GR) gene have been found to alter glucocorticoid sensitivity and have been associated with altered metabolic profiles.
The objective of the study was to examine whether N363S and ER22/23K variants of the GR gene may be associated with the development of adrenal incidentalomas and whether these variants may contribute to metabolic abnormalities frequently present in these patients.
DESIGN, SETTING, AND PATIENTS: The study included 99 patients with unilateral and 44 patients with bilateral adrenal incidentalomas, 102 population-matched control subjects, and 100 patients with type 2 diabetes mellitus.
Metabolic and hormonal parameters and GR gene variants were determined.
When compared with control subjects, the carrier frequency for the N363S variant was markedly and significantly higher in patients with bilateral (7.8 vs. 20.5%, P < 0.05) but not in those with unilateral incidentalomas (7.1%) or in patients with type 2 diabetes (13.0%). Type 2 diabetes occurred more frequently in patients with bilateral, compared with those with unilateral incidentalomas (40.9 vs. 22.2%, P < 0.05). In patients with bilateral incidentalomas, a significant association of the N363S variant with impaired glucose homeostasis but not with body mass index, hypertension, hyperlipidemia, or history of coronary artery disease was found. The carrier frequency of the ER22/23EK variant was similar in all groups, and this variant failed to show any association with metabolic abnormalities.
These results suggest that the N363S variant of the GR gene may play a role in the pathogenesis of bilateral adrenal incidentalomas, although the mechanism still remains to be investigated.
已发现糖皮质激素受体（GR）基因的某些变体可改变糖皮质激素敏感性，并与代谢谱改变有关。
本研究的目的是检查GR基因的N363S和ER22/23K变体是否可能与肾上腺偶发瘤的发生有关，以及这些变体是否可能导致这些患者中经常出现的代谢异常。
设计、地点和患者：该研究纳入了99名单侧肾上腺偶发瘤患者和44名双侧肾上腺偶发瘤患者、102名年龄匹配的对照受试者以及100名2型糖尿病患者。
测定代谢和激素参数以及GR基因变体。
与对照受试者相比，N363S变体的携带频率在双侧肾上腺偶发瘤患者中显著更高（7.8%对20.5%，P<0.05），但在单侧肾上腺偶发瘤患者（7.1%）或2型糖尿病患者（13.0%）中并非如此。与单侧肾上腺偶发瘤患者相比，双侧肾上腺偶发瘤患者中2型糖尿病的发生率更高（40.9%对22.2%，P<0.05）。在双侧肾上腺偶发瘤患者中，发现N363S变体与葡萄糖稳态受损显著相关，但与体重指数、高血压、高脂血症或冠状动脉疾病史无关。ER22/23EK变体的携带频率在所有组中相似，且该变体未显示与代谢异常有任何关联。
这些结果表明，GR基因的N363S变体可能在双侧肾上腺偶发瘤的发病机制中起作用，尽管其机制仍有待研究。
