Expression and Mutations of KCNJ5 mRNA in Japanese Patients with Aldosterone-Producing Adenomas

• Published in: The journal of clinical endocrinology and metabolism 2012-04, Vol.97 (4), p.1311-1319
• Main Authors: Taguchi, Ryo, Yamada, Masanobu, Nakajima, Yasuyo, Satoh, Tetsurou, Hashimoto, Koshi, Shibusawa, Nobuyuki, Ozawa, Atsushi, Okada, Shuichi, Rokutanda, Nana, Takata, Daisuke, Koibuchi, Yukio, Horiguchi, Jun, Oyama, Tetsunari, Takeyoshi, Izumi, Mori, Masatomo
• Format: Article
• Language: English
• Subjects: Adenoma; Adrenal Cortex Neoplasms - genetics; Adrenal Cortex Neoplasms - metabolism; Adrenal Cortex Neoplasms - pathology; Adrenal Cortex Neoplasms - physiopathology; Adrenal Gland Neoplasms - genetics; Adrenal Gland Neoplasms - metabolism; Adrenocortical Adenoma - genetics; Adrenocortical Adenoma - metabolism; Adrenocortical Adenoma - pathology; Adrenocortical Adenoma - physiopathology; Adult; Aged; Base Sequence; Biological and medical sciences; Cell membranes; Cross-Sectional Studies; Cushing Syndrome - genetics; Cushing Syndrome - metabolism; Cushing's syndrome; Endocrinopathies; Feeding. Feeding behavior; Female; Fundamental and applied biological sciences. Psychology; G Protein-Coupled Inwardly-Rectifying Potassium Channels - chemistry; G Protein-Coupled Inwardly-Rectifying Potassium Channels - genetics; G Protein-Coupled Inwardly-Rectifying Potassium Channels - metabolism; Gene expression; Genetic Association Studies; Hospitals; Humans; Hyperaldosteronism - etiology; Immunohistochemistry; Japan; Male; Medical sciences; Middle Aged; Molecular Sequence Data; mRNA; Mutation; Neoplasm Proteins - chemistry; Neoplasm Proteins - genetics; Neoplasm Proteins - metabolism; Pheochromocytoma; Pheochromocytoma - genetics; Pheochromocytoma - metabolism; Retrospective Studies; RNA, Messenger - metabolism; Tumors; Vertebrates: anatomy and physiology, studies on body, several organs or systems; Vertebrates: endocrinology
• ISSN: 0021-972X; 1945-7197
• DOI: 10.1210/jc.2011-2885

Context: Mutations of the KCNJ5 gene have recently been identified in patients with aldosterone-producing adenomas (APA). Objective: Our objective was to investigate the expression and mutations of the KCNJ5 gene in Japanese patients with APA. Design and Patients: We sequenced KCNJ5 cDNA and measured KCNJ5 mRNA levels in 23 patients with APA operated on at Gunma University Hospital. Main Outcome Measures: Mutations and mRNA levels of the KCNJ5 gene were examined and compared to those in cortisol-producing adenomas (Cushing's syndrome) and pheochromocytomas. Results: 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. Conclusion: 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.