Genetics of Aldosterone-Producing Adenoma in Korean Patients.

A Ram Hong,Seong Yeon Kim,Young Shin Song,Sang Wan Kim,Jung Hee Kim,Soo Hyun Seo,Kyu Eun Lee,Moon-Woo Seong,Chan Soo Shin,Obul Reddy Bandapalli

doi:10.1371/journal.pone.0147590

A Ram Hong, Seong Yeon Kim + Show 8 more

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https://doi.org/10.1371/journal.pone.0147590

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Abstract

ObjectivesRecently, somatic mutations in KCNJ5, ATP1A1, ATP2B3, and CACNA1D genes were found to be associated with the pathogenesis of aldosterone-producing adenoma (APA). This study aimed to investigate the prevalence of somatic mutations in KCNJ5, ATP1A1, ATP2B3, and CACNA1D and examine the correlations between these mutations and the clinical and biochemical characteristics in Korean patients with APA.MethodsWe performed targeted gene sequencing in 66 patients with APA to detect somatic mutations in these genes.ResultsSomatic KCNJ5 mutations were found in 47 (71.2%) of the 66 patients with APA (31 cases of p.G151R and 16 cases of p.L168R); these two mutations were mutually exclusive. Somatic mutations in the ATP1A1, ATP2B3, and CACNA1D genes were not observed. Somatic KCNJ5 mutations were more prevalent in female patients (66% versus 36.8%, respectively; P = 0.030). Moreover, patients with KCNJ5 mutations comprised a significantly higher proportion of patients younger than 35 years of age (19.1% versus 0%, respectively; P = 0.040). There were no significant differences in pre-operative blood pressure, plasma aldosterone, serum potassium, lateralization index, and adenoma size according to mutational status. Patients with KCNJ5 mutations were less likely to need antihypertensive medications after adrenalectomy compared with those without mutation (36.2% versus 63.2%; P = 0.045).ConclusionsThe present study demonstrated the high prevalence of somatic KCNJ5 mutations in Korean patients with APA. Carriers of somatic KCNJ5 mutations were more likely to be female. Early diagnosis and better therapeutic outcomes were associated with somatic KCNJ5 mutations in APA.

Highlights

Primary aldosteronism (PA) is the most common cause of secondary hypertension and accounts for 10% or more of hypertension cases
Somatic KCNJ5 mutations were more prevalent in female patients (66% versus 36.8%, respectively; P = 0.030)
There were no significant differences in pre-operative blood pressure, plasma aldosterone, serum potassium, lateralization index, and adenoma size according to mutational status

Summary

Introduction

Primary aldosteronism (PA) is the most common cause of secondary hypertension and accounts for 10% or more of hypertension cases. Mutations in the KCNJ5 gene, which encodes G-protein-activated inward-rectifying K+ channel 4, cause familial hyperaldosteronism type III and sporadic aldosterone-producing adenoma (APA) [3, 4]. These mutations are located near or within the selective filter of the K+ channel, resulting in increased Na+ conductance through loss of ion selective permeability [5]. Subsequent cell membrane depolarization activates voltage-gated Ca2+ channels, thereby stimulating the expression of the CYP11B2 gene, which encodes aldosterone synthase [6]

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