title: The FTO gene polymorphism is associated with end-stage renal disease: two large independent case-control studies in a general population.
abstract: BACKGROUND
  Genome-wide association studies identified the FTO (fat mass and obesity gene) gene as an important determinant of body weight. More recently, the FTO gene was reported to be associated with other outcomes, including major risk factors for chronic kidney disease (CKD). We investigated the role of this gene in the risk of end-stage renal disease (ESRD) caused by CKD.
  
  
  METHODS
  We conducted two large population-based case-control studies of ESRD. Study 1 compared 984 haemodialysed patients with ESRD with 2501 participants in the Czech post-MONICA study; Study 2 compared 1188 patients included in a kidney transplantation programme for ESRD with 6681 participants in the Czech HAPIEE study. The frequencies of the FTO rs17817449 single nucleotide polymorphism genotype were compared between cases and controls.
  
  
  RESULTS
  The FTO rs17817449 genotype was significantly associated with CKD in both studies (P-values 0.00004 and 0.006, respectively). In the pooled data, the odds ratios of CKD for GG and GT, versus TT genotype, were 1.37 (95% confidence interval 1.20-1.56) and 1.17 (1.05-1.31), respectively (P for trend <0.0001). Among haemodialysed and kidney transplant patients, the onset of ESRD in GG homozygotes was 3.3 (P = 0.012) and 2.5 (P = 0.032) years, respectively, earlier than in TT homozygotes.
  
  
  CONCLUSIONS
  These two large independent case-control studies in the general population found robust associations between the FTO rs17817449 polymorphism and the ESRD. The results suggest that the morbidities associated with the FTO gene include CKD.
authors.affiliation: Institute for Clinical and Experimental Medicine, Prague, Czech Republic.
authors.forename: Jaroslav A
authors.initials: JA
authors.lastname: Hubacek
authors.forename: Ondrej
authors.initials: O
authors.lastname: Viklicky
authors.forename: Dana
authors.initials: D
authors.lastname: Dlouha
authors.forename: Silvie
authors.initials: S
authors.lastname: Bloudickova
authors.forename: Ruzena
authors.initials: R
authors.lastname: Kubinova
authors.forename: Anne
authors.initials: A
authors.lastname: Peasey
authors.forename: Hynek
authors.initials: H
authors.lastname: Pikhart
authors.forename: Vera
authors.initials: V
authors.lastname: Adamkova
authors.forename: Irena
authors.initials: I
authors.lastname: Brabcova
authors.forename: Eva
authors.initials: E
authors.lastname: Pokorna
authors.forename: Martin
authors.initials: M
authors.lastname: Bobak
mesh_terms: D000328:Adult; D017668:Age of Onset; D000368:Aged; D000071516:Alpha-Ketoglutarate-Dependent Dioxygenase FTO; D015992:Body Mass Index; D016022:Case-Control Studies; D018153:Czech Republic / Q000453:epidemiology; D004247:DNA / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D007676:Kidney Failure, Chronic / Q000453:epidemiology* / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic / Q000235:genetics*; D011506:Proteins / Q000235:genetics*; D012307:Risk Factors
chemical_list: D011506:Proteins; D004247:DNA; D000071516:Alpha-Ketoglutarate-Dependent Dioxygenase FTO; C526492:FTO protein, human