title: Genetics of Aldosterone-Producing Adenoma in Korean Patients.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  We performed targeted gene sequencing in 66 patients with APA to detect somatic mutations in these genes.
  
  
  RESULTS
  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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea.
authors.forename: A Ram
authors.initials: AR
authors.lastname: Hong
authors.affiliation: Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea.
authors.forename: Jung Hee
authors.initials: JH
authors.lastname: Kim
authors.affiliation: Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea.
authors.forename: Young Shin
authors.initials: YS
authors.lastname: Song
authors.affiliation: Department of Surgery, Seoul National University College of Medicine, Seoul, Republic of Korea.
authors.forename: Kyu Eun
authors.initials: KE
authors.lastname: Lee
authors.affiliation: Department of Laboratory Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea.
authors.forename: Soo Hyun
authors.initials: SH
authors.lastname: Seo
authors.affiliation: Department of Laboratory Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea.
authors.forename: Moon-Woo
authors.initials: MW
authors.lastname: Seong
authors.affiliation: Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea.
authors.forename: Chan Soo
authors.initials: CS
authors.lastname: Shin
authors.affiliation: Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea.|Department of Internal Medicine, Seoul Metropolitan Government Boramae Medical Center, Seoul, Republic of Korea.
authors.forename: Sang Wan
authors.initials: SW
authors.lastname: Kim
authors.affiliation: Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea.
authors.forename: Seong Yeon
authors.initials: SY
authors.lastname: Kim
mesh_terms: D000306:Adrenal Cortex Neoplasms / Q000235:genetics* / Q000378:metabolism; D018246:Adrenocortical Adenoma / Q000235:genetics* / Q000378:metabolism; D000328:Adult; D000367:Age Factors; D000450:Aldosterone / Q000378:metabolism*; D020746:Calcium Channels, L-Type / Q000235:genetics*; D004252:DNA Mutational Analysis; D005260:Female; D051676:G Protein-Coupled Inwardly-Rectifying Potassium Channels / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D053499:Plasma Membrane Calcium-Transporting ATPases / Q000235:genetics*; D056910:Republic of Korea; D012737:Sex Factors; D000254:Sodium-Potassium-Exchanging ATPase / Q000235:genetics*
chemical_list: C472073:CACNA1D protein, human; D020746:Calcium Channels, L-Type; D051676:G Protein-Coupled Inwardly-Rectifying Potassium Channels; C484274:KCNJ5 protein, human; D000450:Aldosterone; C499076:ATP1A1 protein, human; D053499:Plasma Membrane Calcium-Transporting ATPases; C506962:ATP2B3 protein, human; D000254:Sodium-Potassium-Exchanging ATPase