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Cited by 151Hormonal Regulation and HypertensionAdrenal and Paraganglionic TumorsIon channel regulation and function

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

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Zheng, Fang-Fang, Zhu, Li-Min, Nie, Ai-Fang, Li, Xiao-Ying, Lin, Jing-Rong, Zhang, Ke, Chen, Jing, Zhou, Wen-Long +5 more·2015·Hypertension
DOI 10.1161/hypertensionaha.114.03346
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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.

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  • KCNJ5 mutations have been documented in approximately 40% of patients with aldosterone-producing adenomas from European cohorts, with much higher rates reported in patients from Japan and Asia.

    “Mutations in KCNJ5 (potassium channel) have been documented in patients with aldosterone-producing adenomas in approximately 40% of patients (151) from European cohorts, though much higher rates are reported in patients from Japan and Asia (152,153).”

    From Adrenal incidentaloma (2020) · cites this paper as [152]

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Authors
Zheng, F.-F., Zhu, L.-M., Nie, A.-F., Li, X.-Y., Lin, J.-R., Zhang, K., Chen, J., Zhou, W.-L., Shen, Z.-J., Zhu, Y.-C., Wang, J.-G., Zhu, D.-L., & Gao, P.-J.
Affiliations
  • 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...
  • Shanghai Medical College of Fudan University (CN)
ORCID
Venue
Hypertension
Publisher
Ovid Technologies (Wolters Kluwer Health)
Published
2015-03
Volume
65
Issue
3
Pages
622-628
ISSN
  • 0194-911X (ISSN-L)
  • 1524-4563
DOI
10.1161/hypertensionaha.114.03346
OpenAlex
W2116698088
Cited by
151
References
31
Citations by year
2026: 8 · 2025: 7 · 2024: 9 · 2023: 10 · 2022: 11 · 2021: 18 · 2020: 15 · 2019: 15 · 2018: 13 · 2017: 18 · 2016: 15 · 2015: 10 · 2014: 1
FWCI
16.19
Type
journal article
Language
en
Open access
Locations
  • Hypertension (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Natural Science Foundation of China
  • Science and Technology Commission of Shanghai Municipality
  • Shanghai Jiao Tong University
  • Ruijin Hospital
  • School of Medicine, Shanghai Jiao Tong University
Topics
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Hormonal Regulation and Hypertension
  • Health Sciences › Medicine › Surgery › Adrenal and Paraganglionic Tumors
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ion channel regulation and function
Keywords
aldosterone-producing adenoma, somatic mutations, KCNJ5, ATP1A1, ATP2B3, CACNA1D, Chinese patients, aldosterone excretion, serum potassium, potassium channel selectivity, membrane depolarization, calcium signaling
MeSH terms
Sodium-Potassium-Exchanging ATPase, Adrenal Cortex Neoplasms, Adult, Aldosterone, Base Sequence, Female, Humans, Male, Middle Aged, Molecular Sequence Data, Mutation, Phenotype, Potassium, Retrospective Studies, Sex Factors, Prevalence, Adrenocortical Adenoma, Calcium Channels, L-Type, Asian People, Tumor Burden, G Protein-Coupled Inwardly-Rectifying Potassium Channels, Plasma Membrane Calcium-Transporting ATPases

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