Open AccessThe prevalence of CTNNB1 mutations in primary aldosteronism and consequences for clinical outcomes
Author(s) -
VinCent Wu,
Shuo-Meng Wang,
Shih-Chieh Chueh,
Shan-Yi Yang,
KuoHow Huang,
YenHung Lin,
Jian-Jhong Wang,
Rory Connolly,
Yahui Hu,
Celso E. Gómez-Sánchez,
Kang-Yung Peng,
KwanDun Wu
Publication year - 2017
Publication title -
scientific reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.24
H-Index - 213
ISSN - 2045-2322
DOI - 10.1038/srep39121
Subject(s) - primary aldosteronism , aldosterone , wnt signaling pathway , steroid 11 beta hydroxylase , aldosterone synthase , carcinogenesis , mutation , adrenalectomy , medicine , hyperaldosteronism , adenoma , germline mutation , endocrinology , cancer research , biology , genetics , hormone , signal transduction , renin–angiotensin system , gene , cancer , steroid , blood pressure
Constitutive activation of the Wnt pathway/β-catenin signaling may be important in aldosterone-producing adenoma (APA). However, significant gaps remain in our understanding of the prevalence and clinical outcomes after adrenalectomy in APA patients harboring CTNNB1 mutations. The molecular expression of CYP11B2 and gonadal receptors in adenomas were also explored. Adenomas from 219 APA patients (95 men; 44.2%; aged 50.5 ± 11.9 years) showed a high rate of somatic mutations (n = 128, 58.4%). The majority of them harbored KCNJ5 mutations (n = 116, 52.9%); 8 patients (3.7%, 6 women) had CTNNB1 mutations. Patients with APAs harboring CTNNB1 mutations were older and had shorter duration of hypertension. After adrenalectomy, CTNNB1 mutation carriers had a higher possibility (87.5%) of residual hypertension than other APA patients. APAs harboring CTNNB1 mutations have heterogeneous staining of β-catenin and variable expression of gonadal receptors and both CYP11B1 and CYP11B2. This suggests that CTNNB1 mutations may be more related to tumorigenesis rather than excessive aldosterone production.