KCNJ5 mutations in Japanese patients with aldosterone-producing adenomas

M. Yamada; R. Taguchi; Y. Nakajima; T. Satoh; K. Hashimoto; N. Shibusawa; A. Ozawa; T. Tomaru; S. Okada; N. Rokutanda; D. Takata; Y. Koibuchi; J. Horiguchi; T. Oyama; I. Takeyoshi; M. Mori

Background: Primary aldosteronism (PA) has been reported to affect about 10% of patients with essential hypertension. In Western countries, about one third of them have aldosterone-producing adenomas (APA), and mutations of the KCNJ5 gene have recently been identified in approximately 30% of APAs. In contrast, most Japanese (~80%) with PA have APA. Therefore, Japanese PA may have different characteristics from patients in Western countries, and those with mutations of the KCNJ5 gene may have different features from those without.

Design: We sequenced KCNJ5 cDNAs in 25 tumors from patients with APA operated on at Gunma University Hospital and compared their clinicopathological features between patients with and without mutations. In addition, we investigated levels of KCNJ5 mRNA in the two groups and compared to those in cortisol-producing adenomas (Cushing’s syndrome) and pheochromocytomas.

Results: Of the 25 patients with APA, 16 (64%) had two recurrent somatic mutations of the KCNJ5 gene: 12 cases of p.G151R (8 with c.451G > A, and 4 with c.451G > C) and 4 cases of p.L168R (c.503T > G). Levels of KCNJ5 mRNA were significantly higher in the APAs with mutations than those without. Immunohistochemistry also showed a stronger staining of KCNJ5 on the cell membrane in the tumor with a mutation. The level of KCNJ5 mRNA in cortisol-producing adenomas was approximately 30% of that in APAs, and almost no expression was observed in pheochromocytomas. In addition, the patients with mutations were statistically younger and showed higher plasma aldosterone concentrations and lower serum potassium levels.

Conclusions: i) We identified a high prevalence of mutations of the KCNJ5 gene in Japanese patients with APA, ii) KCNJ5 mRNA levels were higher in the APAs with KCNJ5 mutations, and iii) the expression of KCNJ5 mRNA was significantly higher in APAs than cortisol-producing adenomas and pheochromocytomas, and iv) patients with APAs associated with somatic mutations of the KCNJ5 gene may exhibit early onset and high serum aldosterone level.

Declaration of interest: The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research project.

Funding: This research did not receive any specific grant from any funding agency in the public, commercial or not-for-profit sector.

Endocrine Abstracts

OC13.5