Genetics of Aldosterone-Producing Adenoma in Korean Patients

• Published in: PloS one 2016-01, Vol.11 (1), p.e0147590-e0147590
• Main Authors: Hong, A Ram, Kim, Jung Hee, Song, Young Shin, Lee, Kyu Eun, Seo, Soo Hyun, Seong, Moon-Woo, Shin, Chan Soo, Kim, Sang Wan, Kim, Seong Yeon
• Format: Article
• Language: English
• Subjects: Adenoma; Adrenal Cortex Neoplasms - genetics; Adrenal Cortex Neoplasms - metabolism; Adrenalectomy; Adrenocortical Adenoma - genetics; Adrenocortical Adenoma - metabolism; Adult; Age Factors; Aldosterone; Aldosterone - metabolism; Antihypertensives; Biochemical characteristics; Biochemistry; Biology and Life Sciences; Blood pressure; Calcium Channels, L-Type - genetics; Cancer genetics; Computer and Information Sciences; Deoxyribonucleic acid; Development and progression; DNA; DNA Mutational Analysis; Endocrine disorders; Endocrinology; Female; G Protein-Coupled Inwardly-Rectifying Potassium Channels - genetics; Gene sequencing; Genes; Genetic aspects; Genetics; Humans; Hypertension; Internal medicine; Laboratories; Male; Medicine; Medicine and Health Sciences; Metabolism; Middle Aged; Mutation; Pathogenesis; Patients; Physicians; Physiological aspects; Plasma; Plasma Membrane Calcium-Transporting ATPases - genetics; Potassium; Republic of Korea; Rodents; Sex Factors; Sodium-Potassium-Exchanging ATPase - genetics; Tumors
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0147590

Recently, 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. We performed targeted gene sequencing in 66 patients with APA to detect somatic mutations in these genes. Somatic 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). The 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.