Referenced in: none

Automatically associated channels: Cav1.3 , Kir3.4

Title: Clinical characteristics of somatic mutations in Chinese patients with aldosterone-producing adenoma.

Authors: Fang-Fang Zheng, Li-Min Zhu, Ai-Fang Nie, Xiao-Ying Li, Jing-Rong Lin, Ke Zhang, Jing Chen, Wen-Long Zhou, Zhou-Jun Shen, Yi-Chun Zhu, Ji-Guang Wang, Ding-Liang Zhu, Ping-Jin Gao

Journal, date & volume: Hypertension, 2015 Mar , 65, 622-8

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/25624344

Abstract
Recent studies have shown that somatic mutations in the KCNJ5, ATP1A1, ATP2B3, and CACNA1D genes are associated with the pathogenesis of aldosterone-producing adenoma. Clinical profile and biochemical characteristics of the mutations in Chinese patients with aldosterone-producing adenoma remain unclear. In this study, we performed DNA sequencing in 168 Chinese patients with aldosterone-producing adenoma and found 129 somatic mutations in KCNJ5, 4 in ATP1A1, 1 in ATP2B3, and 1 in CACNA1D. KCNJ5 mutations were more prevalent in female patients and were associated with larger adenomas, higher aldosterone excretion, and lower minimal serum K(+) concentration. More interestingly, we identified a novel somatic KCNJ5 mutation (c.445-446insGAA, p.T148-T149insR) that could enhance CYP11B2 mRNA upregulation and aldosterone release. This mutation could also cause membrane depolarization and intercellular Ca(2+) increase. In conclusion, somatic KCNJ5 mutations are conspicuously more popular than mutations of other genes in aldosterone-producing adenomas of Chinese patients. The T148-T149insR mutation in KCNJ5 may influence K(+) channel selectivity and autonomous aldosterone production.