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

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

doi:10.1161/HYPERTENSIONAHA.114.03346

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

Hypertension. 2015 Mar;65(3):622-8. doi: 10.1161/HYPERTENSIONAHA.114.03346. Epub 2015 Jan 26.

Authors

Affiliations

¹ From the State Key Laboratory of Medical Genomics, Shanghai Key Laboratory of Hypertension and Department of Hypertension, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China (F.-F.Z., L.-M.Z., J.C., J.-G.W., D.-L.Z., P.-J.G.); Laboratory of Vascular Biology and Key Laboratory of Stem Cell Biology, Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China (F.-F.Z., J.-R.L., K.Z., P.-J.G.); Shanghai Institute of Hypertension (F.-F.Z., L.-M.Z., J.C., J.-G.W., D.-L.Z., P.-J.G.), Shanghai Institute of Endocrinology and Metabolism (A.-F.N., X.-Y.L.), and Department of Urology, Ruijin Hospital (W.-L.Z., Z.-J.S.), Shanghai Jiao Tong University School of Medicine, Shanghai, China; and Department of Physiology and Pathophysiology, Shanghai Medical College, Fudan University, Shanghai, China (Y.-C.Z.).
² From the State Key Laboratory of Medical Genomics, Shanghai Key Laboratory of Hypertension and Department of Hypertension, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China (F.-F.Z., L.-M.Z., J.C., J.-G.W., D.-L.Z., P.-J.G.); Laboratory of Vascular Biology and Key Laboratory of Stem Cell Biology, Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China (F.-F.Z., J.-R.L., K.Z., P.-J.G.); Shanghai Institute of Hypertension (F.-F.Z., L.-M.Z., J.C., J.-G.W., D.-L.Z., P.-J.G.), Shanghai Institute of Endocrinology and Metabolism (A.-F.N., X.-Y.L.), and Department of Urology, Ruijin Hospital (W.-L.Z., Z.-J.S.), Shanghai Jiao Tong University School of Medicine, Shanghai, China; and Department of Physiology and Pathophysiology, Shanghai Medical College, Fudan University, Shanghai, China (Y.-C.Z.). [email protected].

PMID: 25624344
DOI: 10.1161/HYPERTENSIONAHA.114.03346

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.

Keywords: KCNJ5; aldosterone; hypertension; potassium channel; somatic mutation.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adrenal Cortex Neoplasms / genetics*
Adrenal Cortex Neoplasms / metabolism*
Adrenocortical Adenoma / genetics*
Adrenocortical Adenoma / metabolism*
Adult
Aldosterone / metabolism*
Asian People / genetics*
Base Sequence
Calcium Channels, L-Type / genetics
Female
G Protein-Coupled Inwardly-Rectifying Potassium Channels / genetics
Humans
Male
Middle Aged
Molecular Sequence Data
Mutation / genetics*
Phenotype*
Plasma Membrane Calcium-Transporting ATPases / genetics
Potassium / blood
Prevalence
Retrospective Studies
Sex Factors
Sodium-Potassium-Exchanging ATPase / genetics
Tumor Burden

Substances

CACNA1D protein, human
Calcium Channels, L-Type
G Protein-Coupled Inwardly-Rectifying Potassium Channels
KCNJ5 protein, human
Aldosterone
ATP1A1 protein, human
Plasma Membrane Calcium-Transporting ATPases
ATP2B3 protein, human
Sodium-Potassium-Exchanging ATPase
Potassium