title: The fat-mass and obesity-associated gene (FTO) predicts mortality in chronic kidney disease of various severity.
abstract: BACKGROUND
  Polymorphisms in the FTO (fat-mass and obesity-associated) gene have been associated with the body mass index, cancer, type 2 diabetes and hypertension.
  
  
  METHODS
  We investigated the relationship between 17 tag single-nucleotide polymorphisms (SNPs) and all-cause mortality in three cohorts of dialysis patients (CREED-1, North Apulian and CREED-2 cohorts; n = 783) and in one cohort of stage 2-5 CKD patients (n = 757).
  
  
  RESULTS
  We first explored the association between the 17 tag SNPs and all-cause mortality in the CREED-1 cohort and found that patients with the A allele of the FTO rs708259 polymorphism had an elevated risk of mortality (hazard ratio, HR: 1.52, 95% confidence interval (CI) 1.11-2.08; P = 0.008). Similarly, the A allele was associated with an increased risk of death also in the other two dialysis cohorts (North Apulian cohort, risk: +23%; CREED-2 cohort, risk: +21%). The elevated risk portended by this allele was even higher in the stage 2-5 CKD cohort (+97%). However, the risk of mortality associated with the A allele in the three confirmatory cohorts failed to achieve formal statistical significance. In a meta-analysis including the four cohorts (n = 1540; total deaths, n = 381), individuals with the A allele had a 42% excess risk of death (HR: 1.42, 95% CI 1.14-1.76, P = 0.002).
  
  
  CONCLUSIONS
  The A allele of the FTO rs708259 polymorphism is an independent predictor of all-cause mortality in patients with CKD of various severity. These data support our hypothesis that the FTO gene may be a relevant genetic risk factor for mortality in this population.
authors.affiliation: CNR-IBIM and Nephrology, Dialysis and Transplantation Unit of Reggio Calabria, Reggio Calabria, Italy.
authors.forename: Belinda
authors.initials: B
authors.lastname: Spoto
authors.forename: Francesco
authors.initials: F
authors.lastname: Mattace-Raso
authors.forename: Eric
authors.initials: E
authors.lastname: Sijbrands
authors.forename: Francesca
authors.initials: F
authors.lastname: Mallamaci
authors.forename: Daniela
authors.initials: D
authors.lastname: Leonardis
authors.forename: Filippo
authors.initials: F
authors.lastname: Aucella
authors.forename: Alessandra
authors.initials: A
authors.lastname: Testa
authors.forename: Antonio
authors.initials: A
authors.lastname: Gesuete
authors.forename: Maria C
authors.initials: MC
authors.lastname: Sanguedolce
authors.forename: Graziella
authors.initials: G
authors.lastname: D'Arrigo
authors.forename: Rosa M
authors.initials: RM
authors.lastname: Parlongo
authors.forename: Anna
authors.initials: A
authors.lastname: Pisano
authors.forename: Claudia
authors.initials: C
authors.lastname: Torino
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Enia
authors.forename: Giovanni
authors.initials: G
authors.lastname: Tripepi
authors.forename: Maurizio
authors.initials: M
authors.lastname: Postorino
authors.forename: Carmine
authors.initials: C
authors.lastname: Zoccali
mesh_terms: D000071516:Alpha-Ketoglutarate-Dependent Dioxygenase FTO; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D011506:Proteins / Q000235:genetics*; D051436:Renal Insufficiency, Chronic / Q000235:genetics* / Q000401:mortality*; D012720:Severity of Illness Index
chemical_list: D011506:Proteins; D000071516:Alpha-Ketoglutarate-Dependent Dioxygenase FTO; C526492:FTO protein, human