title: A Meta-Analysis of Somatic KCNJ5 K(+) Channel Mutations In 1636 Patients With an Aldosterone-Producing Adenoma.
abstract: BACKGROUND
  Due to selection biases and inadequate statistical power, individual studies may fail to identify the clinical features of patients with an aldosterone-producing adenoma (APA) harboring KCNJ5 mutations. When this failure occurs, meta-analysis can provide significant outcome data.
  
  
  OBJECTIVE
  The objective was to determine the clinical features of these APA patients.
  
  
  METHODS
  We systematically searched the PubMed, Scopus, Web of Science, and Cochrane databases library in January 2015 applying the Population, Intervention, Comparison, and Outcome (PICO) strategy. The standardized differences in mean and corresponding 95% confidence interval of continuous variables were computed by random-effects modeling.
  
  
  METHODS
  We performed a meta-analysis of all available studies on somatic KCNJ5 mutations in APA.
  
  
  METHODS
  We could identify 13 studies that recruited 1636 patients (age 49 ± 4 years; 55% females).
  
  
  METHODS
  Differences between APA with and without KCNJ5 mutations in gender, plasma renin activity, plasma aldosterone, tumor size, serum potassium, and blood pressure were investigated.
  
  
  RESULTS
  The overall prevalence of KCNJ5 mutations was 43% (range = 12-80%). Their rate was lower (P < .003) in the studies done in Europe, the United States, and Australia (35%) than in Japan and China (63%); it correlated (r = 0.60, P = .029) with the mean daily urinary sodium excretion. Compared with the wild-type, the mutated APA patients were younger (45 ± 3 vs 52 ± 5 yrs), had higher plasma aldosterone (42 ± 8 vs 33 ± 8 ng/dl), larger tumors (16.1 ± 6.4 versus 14.9 ± 7.4 mm), and were more often females (67% vs 44%) (all P < .05).
  
  
  CONCLUSIONS
  Meta-analysis showed that more pronounced hyperaldosteronism, young age, female gender, and larger tumors are the phenotypic features of APA patients with KCNJ5 mutations. No significant differences in blood pressure and serum K(+) was found, which suggests that these clinical features do not help in identifying mutated APA patients.
authors.affiliation: Department of Medicine-DIMED (L.L., G.R., G.M., G.P.R.), Clinica dell'Ipertensione Arteriosa, University of Padua, Italy; Department of Internal Medicine and Medical Specialties (C.L.), University of Rome 'Sapienza', Rome, Italy; and The Hudson Medical Research Institute (J.W.F.), Clayton 3168, Australia.
authors.forename: Livia
authors.initials: L
authors.lastname: Lenzini
authors.affiliation: Department of Medicine-DIMED (L.L., G.R., G.M., G.P.R.), Clinica dell'Ipertensione Arteriosa, University of Padua, Italy; Department of Internal Medicine and Medical Specialties (C.L.), University of Rome 'Sapienza', Rome, Italy; and The Hudson Medical Research Institute (J.W.F.), Clayton 3168, Australia.
authors.forename: Giacomo
authors.initials: G
authors.lastname: Rossitto
authors.affiliation: Department of Medicine-DIMED (L.L., G.R., G.M., G.P.R.), Clinica dell'Ipertensione Arteriosa, University of Padua, Italy; Department of Internal Medicine and Medical Specialties (C.L.), University of Rome 'Sapienza', Rome, Italy; and The Hudson Medical Research Institute (J.W.F.), Clayton 3168, Australia.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Maiolino
authors.affiliation: Department of Medicine-DIMED (L.L., G.R., G.M., G.P.R.), Clinica dell'Ipertensione Arteriosa, University of Padua, Italy; Department of Internal Medicine and Medical Specialties (C.L.), University of Rome 'Sapienza', Rome, Italy; and The Hudson Medical Research Institute (J.W.F.), Clayton 3168, Australia.
authors.forename: Claudio
authors.initials: C
authors.lastname: Letizia
authors.affiliation: Department of Medicine-DIMED (L.L., G.R., G.M., G.P.R.), Clinica dell'Ipertensione Arteriosa, University of Padua, Italy; Department of Internal Medicine and Medical Specialties (C.L.), University of Rome 'Sapienza', Rome, Italy; and The Hudson Medical Research Institute (J.W.F.), Clayton 3168, Australia.
authors.forename: John W
authors.initials: JW
authors.lastname: Funder
authors.affiliation: Department of Medicine-DIMED (L.L., G.R., G.M., G.P.R.), Clinica dell'Ipertensione Arteriosa, University of Padua, Italy; Department of Internal Medicine and Medical Specialties (C.L.), University of Rome 'Sapienza', Rome, Italy; and The Hudson Medical Research Institute (J.W.F.), Clayton 3168, Australia.
authors.forename: Gian Paolo
authors.initials: GP
authors.lastname: Rossi
mesh_terms: D000236:Adenoma / Q000453:epidemiology / Q000235:genetics / Q000378:metabolism; D000306:Adrenal Cortex Neoplasms / Q000453:epidemiology / Q000235:genetics / Q000378:metabolism; D000328:Adult; D000450:Aldosterone / Q000378:metabolism*; D005260:Female; D051676:G Protein-Coupled Inwardly-Rectifying Potassium Channels / Q000235:genetics*; D005787:Gene Frequency; D056726:Genetic Association Studies / Q000706:statistics & numerical data; D006801:Humans; D006929:Hyperaldosteronism / Q000453:epidemiology / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009154:Mutation
chemical_list: D051676:G Protein-Coupled Inwardly-Rectifying Potassium Channels; C484274:KCNJ5 protein, human; D000450:Aldosterone