Department of Medicine and Molecular Science, Gunma University Graduate School of Medicine, 3-39-15 Showa-machi, Maebashi, Gunma 371-8511, Japan.
J Clin Endocrinol Metab. 2012 Apr;97(4):1311-9. doi: 10.1210/jc.2011-2885. Epub 2012 Jan 25.
Mutations of the KCNJ5 gene have recently been identified in patients with aldosterone-producing adenomas (APA).
Our objective was to investigate the expression and mutations of the KCNJ5 gene in Japanese patients with APA.
We sequenced KCNJ5 cDNA and measured KCNJ5 mRNA levels in 23 patients with APA operated on at Gunma University Hospital.
Mutations and mRNA levels of the KCNJ5 gene were examined and compared to those in cortisol-producing adenomas (Cushing's syndrome) and pheochromocytomas.
Of the 23 patients with APA, 15 (65.2%) had two somatic mutations of the KCNJ5 gene: 12 cases of p.G151R (eight with c.451G>A, and four with c.451G>C) and three cases of p.L168R (c.503T>G). Levels of KCNJ5 mRNA were significantly higher in the APA with mutations than those without. Immunohistochemistry also showed a stronger staining of KCNJ5 on the cell membrane in the tumor with a mutation. Furthermore, a PCR-restriction fragment length polymorphism assay with c.503T>G revealed the mutant mRNA to be expressed at a similar level to the wild type. The level of KCNJ5 mRNA in cortisol-producing adenomas was approximately 30% of that in APA, and almost no expression was observed in pheochromocytomas.
We found that: 1) a significant number of patients with APA had somatic mutations of the KCNJ5 gene; 2) KCNJ5 mRNA levels were higher in the APA with KCNJ5 mutations; and 3) the expression of KCNJ5 mRNA was significantly higher in APA than cortisol-producing adenomas and pheochromocytomas.
最近已经在产生醛固酮的腺瘤（APA）患者中鉴定出 KCNJ5 基因突变。
我们的目的是研究 KCNJ5 基因在日本 APA 患者中的表达和突变情况。
我们对在群马大学医院接受手术的 23 例 APA 患者的 KCNJ5 cDNA 进行了测序，并测量了 KCNJ5 mRNA 水平。
检查 KCNJ5 基因的突变和 mRNA 水平，并与皮质醇产生腺瘤（库欣综合征）和嗜铬细胞瘤进行比较。
在 23 例 APA 患者中，有 15 例（65.2%）存在 KCNJ5 基因的两个体细胞突变：12 例 p.G151R（8 例 c.451G>A，4 例 c.451G>C）和 3 例 p.L168R（c.503T>G）。突变型 APA 的 KCNJ5 mRNA 水平明显高于无突变型。免疫组织化学也显示突变型肿瘤细胞膜上 KCNJ5 的染色更强。此外，c.503T>G 的 PCR 限制性片段长度多态性分析显示突变型 mRNA 的表达与野生型相似。皮质醇产生腺瘤的 KCNJ5 mRNA 水平约为 APA 的 30%，而在嗜铬细胞瘤中几乎没有表达。
我们发现：1）相当数量的 APA 患者存在 KCNJ5 基因突变；2）KCNJ5 基因突变型 APA 的 KCNJ5 mRNA 水平较高；3）KCNJ5 mRNA 的表达在 APA 中明显高于皮质醇产生腺瘤和嗜铬细胞瘤。
