title: European rational approach for the genetics of diabetic complications--EURAGEDIC: patient populations and strategy.
abstract: BACKGROUND
  Diabetic nephropathy is likely to be a complex genetic trait. To date, most diabetic nephropathy candidate gene studies have tested a limited number of genes and variants in small sized populations, or in populations that were poorly matched or phenotyped. The main objective of the EURAGEDIC study was to address these problems.
  
  
  METHODS
  Single nucleotide polymorphisms (SNPs) in candidate genes were tested for association with overt diabetic nephropathy (persistent albuminuria >300 mg/24 h) in a large (n=2499) Type 1 diabetes case/control study. Testing for transmission disequilibrium in 541 independent parent-offspring trios with or without diabetic nephropathy was applied for validation of consistency. Candidate genes were selected based on previous linkage studies, knowledge of metabolic pathways, and animal models. A comprehensive SNP discovery in more than 100 candidate genes was performed by direct sequencing.
  
  
  RESULTS
  In total, 1176 cases with diabetic nephropathy and 1323 diabetic controls with longstanding normoalbuminuria were included from three European populations (Denmark, Finland, France). Data were collected on HbA(1c), blood pressure, urinary albumin excretion rate, kidney function, retinopathy, smoking, medication and cardiovascular disease. To summarize the relevant non-genetic predictors for diabetic nephropathy a baseline phenotypic model fitted to EURAGEDIC data included the covariates: sex, diabetes duration, HbA(1c) and smoking as well as pair-wise interactions.
  
  
  CONCLUSIONS
  The EURAGEDIC study is designed and powered to identify and validate common alleles as genetic risk factors for diabetic nephropathy in Type 1 diabetic patients.
authors: Steno Diabetes Center, Copenhagen, Denmark. ltar@steno.dk
authors: Lise
authors: L
authors: Tarnow
authors: Per-Henrik
authors: PH
authors: Groop
authors: Samy
authors: S
authors: Hadjadj
authors: Gbenga
authors: G
authors: Kazeem
authors: Francois
authors: F
authors: Cambien
authors: Michel
authors: M
authors: Marre
authors: Carol
authors: C
authors: Forsblom
authors: Hans-Henrik
authors: HH
authors: Parving
authors: David
authors: D
authors: Trégouët
authors: Alexandre
authors: A
authors: Thévard
authors: Martin
authors: M
authors: Farrall
authors: Ivo
authors: I
authors: Gut
authors: Dominique
authors: D
authors: Gauguier
authors: Roger
authors: R
authors: Cox
authors: Fumihiko
authors: F
authors: Matsuda
authors: Mark
authors: M
authors: Lathrop
authors: Nathalie
authors: N
authors: Vionnet
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics*; D003928:Diabetic Nephropathies / Q000235:genetics*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged