Prevalence and Clinical Correlates of Somatic Mutation in Aldosterone Producing Adenoma-Taiwanese population

Abstract

Primary aldosteronism (PA) is a common form of secondary hypertension and has significant cardiovascular consequences. Mutated channelopathy due to activation of calcium channels has recently been described in aldosterone-producing adenoma (APA). The aim of this study was to investigate the prevalence of somatic mutations in these key genes in unselected patients and their clinical and cardio-metabolic parameters and molecular correlates. The study involved 148 consecutive PA patients, (66 males; aged 56.3 ± 12.3years) identified by modified four corners rules who received adrenalectomy, 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. 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 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.