Prevalence and clinical correlates of somatic mutation in aldosterone producing adenoma-Taiwanese population.

Vin-Cent Wu,Chin-Chen Chang,Shuo-Meng Wang,Kang-Yung Peng,Tzong-Shinn Chu,Che-Hsiung Wu,Shuei-Liong Lin,Kwan-Dun Wu,Lian-Yu Lin,Kuo-How Huang,Yao-Chou Tsai,Shao-Yu Yang,Yen-Hung Lin

doi:10.1038/srep11396

Abstract

Primary aldosteronism (PA) is a common form of secondary hypertension and has significant cardiovascular consequences. Mutated channelopathy due to the activation of calcium channels has been recently described in aldosterone-producing adenoma (APA). The study involved 148 consecutive PA patients, (66 males; aged 56.3 ± 12.3years) who received adrenalectomy, and were collected from the Taiwan PA investigator (TAIPAI) group. A high rate of somatic mutation in APA was found (n = 91, 61.5%); including mutations in KCNJ5 (n = 88, 59.5%), ATP1A1 (n = 2, 1.4%), and ATP2B3 (n = 1, 0.7%); however, no mutations in CACNA1D were identified. Mutation-carriers were younger (<0.001), had lower Cyst C (p = 0.042), pulse wave velocity (p = 0.027), C-reactive protein (p = 0.042) and a lower rate of proteinuria (p = 0.031) than non-carriers. After multivariate adjustment, mutation carriers had lower serum CRP levels than non-carriers (p = 0.031. Patients with mutation also had a greater chance of recovery from hypertension after operation (p = 0.005). A high incidence of somatic mutations in APA was identified in the Taiwanese population. Mutation-carriers had lower CRP levels and a higher rate of cure of hypertension after adrenalectomy. This raises the possibility of using mutation screening as a tool in predicting long-term outcome after adrenalectomy.

Highlights

By the augmentation of intracellular calcium levels via channelopathies and pumps, which lead to depolarization of zona glomerulosa cells in the adrenal cortex[11,12]
The main finding of this multicenter study is that nearly two thirds of these Taiwanese aldosterone producing adenoma (APA) patients had candidate somatic mutations, almost all in KCNJ5, and the prevalence was higher than previously reported in Caucasian subjects[29,34]
Our results reinforce the view that patients with somatic mutations are younger; mutation carriers and non-carriers had similar degrees of arterial stiffness, proteinuria and left ventricular hypertrophy after multivariate adjustment, suggesting that, despite mutation carriers having an earlier onset of the disease, this does not translate into a unique cardiovascular phenotype[35,36]

Summary

Introduction

By the augmentation of intracellular calcium levels via channelopathies and pumps, which lead to depolarization of zona glomerulosa cells in the adrenal cortex[11,12]. Aldosterone is recognized as an increasingly important contributor to cardiometabolic pathology via informatory non-genomic pathways, in addition to its classically described genomic role in sodium and volume-related regulation[13,14], its effect on cardio-metabolic factors in patients harboring these mutations has yet to be characterized. Previous findings are contradictory with regard to whether KCNJ5 mutations translate into a specific phenotype[15]. We have analyzed 148 APAs, diagnosed and surgically removed by the Taiwan Primary Aldosteronism investigator (TAIPAI) study group, for somatic mutations in KCNJ5, ATP1A1, ATP2B3 and CACNA1D. We searched for clinical correlations and determined the impact on patients who harbored these mutations, focusing on their cardio-metabolic properties

Methods

Results

Conclusion