title: Somatic mutations in the KCNJ5 gene raise the lateralization index: implications for the diagnosis of primary aldosteronism by adrenal vein sampling.
abstract: BACKGROUND
  Somatic mutations in the selectivity filter of KCNJ5 K(+) channel were found to be associated with higher plasma aldosterone concentrations in the patients with an aldosterone-producing adenoma (APA).
  
  
  OBJECTIVE
  We investigated whether plasma aldosterone levels and the lateralization index are higher from the side with the APA with the mutation, as compared with those without the mutation.
  
  
  METHODS
  From 170 consecutive APA patients with comprehensive clinical and KCNJ5 data and a conclusive diagnosis, we recruited 91 patients with adrenal vein sampling and follow-up data. We measured CYP11B1 and CYP11B2 mRNA in APA tissue and plasma aldosterone (PAC) and plasma cortisol concentrations (PCC) in adrenal vein blood. To determine whether KCNJ5 mutations affected aldosterone output from the APA, we calculated the lateralization index (defined as the ratio of PAC to PCC at the APA side over the PAC to PCC ratio at the contralateral side). We also calculated two indexes of the aldosterone production from the APA side and the contralateral suppression index.
  
  
  RESULTS
  The mRNA content of CYP11B2, but not of CYP11B1, and, accordingly, the lateralization index was higher (29.9 ± 7.4 vs. 10.3 ± 3.6, P < 0.02) in the APA with the mutation than in the APA without the mutation.
  
  
  CONCLUSIONS
  APA patients with the somatic KCNJ5 mutations showed a higher production of aldosterone than those without such mutations, which translates in a higher lateralization index. Thus, they are more likely to be identified at adrenal vein sampling and therefore to receive adrenalectomy.
authors.affiliation: Internal Medicine 4, Department of Medicine-DIMED, University of Padua, 35126 Padua, Italy.
authors.forename: Teresa M
authors.initials: TM
authors.lastname: Seccia
authors.forename: Franco
authors.initials: F
authors.lastname: Mantero
authors.forename: Claudio
authors.initials: C
authors.lastname: Letizia
authors.forename: Maniselvan
authors.initials: M
authors.lastname: Kuppusamy
authors.forename: Brasilina
authors.initials: B
authors.lastname: Caroccia
authors.forename: Marlena
authors.initials: M
authors.lastname: Barisa
authors.forename: Maria Verena
authors.initials: MV
authors.lastname: Cicala
authors.forename: Diego
authors.initials: D
authors.lastname: Miotto
authors.forename: Gian Paolo
authors.initials: GP
authors.lastname: Rossi
mesh_terms: D000306:Adrenal Cortex Neoplasms / Q000150:complications / Q000175:diagnosis / Q000235:genetics / Q000378:metabolism; D000311:Adrenal Glands / Q000098:blood supply*; D018246:Adrenocortical Adenoma / Q000150:complications / Q000175:diagnosis / Q000235:genetics / Q000378:metabolism; D000450:Aldosterone / Q000378:metabolism; D005260:Female; D007839:Functional Laterality / Q000502:physiology*; D051676:G Protein-Coupled Inwardly-Rectifying Potassium Channels / Q000235:genetics* / Q000502:physiology; D006305:Health Status Indicators; D006801:Humans; D006929:Hyperaldosteronism / Q000097:blood / Q000175:diagnosis* / Q000209:etiology / Q000235:genetics; D008297:Male; D009154:Mutation / Q000502:physiology*; D018962:Phlebotomy / Q000379:methods*; D011237:Predictive Value of Tests; D014680:Veins
chemical_list: D051676:G Protein-Coupled Inwardly-Rectifying Potassium Channels; C484274:KCNJ5 protein, human; D000450:Aldosterone