The fat-mass and obesity-associated gene (FTO) predicts mortality in chronic kidney disease of various severity

Belinda Spoto, Francesco Mattace-Raso, Eric Sijbrands, Francesca Mallamaci, Daniela Leonardis, Filippo Aucella, Alessandra Testa, Antonio Gesuete, Maria C. Sanguedolce, Graziella D'Arrigo, Rosa M. Parlongo, Anna Pisano, Claudia Torino, Giuseppe Enia, Giovanni Tripepi, Maurizio Postorino, Carmine Zoccali

Research output: Contribution to journalArticlepeer-review

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).ConclusionThe 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.

Original languageEnglish
JournalNephrology Dialysis Transplantation
Volume27
Issue numberSUPPL.4
DOIs
Publication statusPublished - Dec 2012

Keywords

  • chronic kidney disease
  • dialysis
  • FTO gene
  • meta-analysis
  • mortality

ASJC Scopus subject areas

  • Nephrology
  • Transplantation

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