TY - JOUR
T1 - European rational approach for the genetics of diabetic complications--EURAGEDIC
T2 - patient populations and strategy
AU - Tarnow, Lise
AU - Groop, Per-Henrik
AU - Hadjadj, Samy
AU - Kazeem, Gbenga R
AU - Cambien, Francois
AU - Marre, Michel
AU - Forsblom, Carol
AU - Parving, Hans-Henrik
AU - Tregouet, David
AU - Thévard, Alexandre
AU - Farrall, Martin
AU - Gut, Ivo
AU - Gauguier, Dominique
AU - Cox, Roger D
AU - Matsuda, Fumihiko
AU - Lathrop, Mark
AU - Vionnet, Nathalie
AU - EURAGEDIC Consortium
PY - 2008/1
Y1 - 2008/1
N2 - 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.
AB - 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.
KW - Adult
KW - Case-Control Studies
KW - Diabetes Mellitus, Type 1
KW - Diabetic Nephropathies
KW - Female
KW - Humans
KW - Male
KW - Middle Aged
KW - Journal Article
KW - Multicenter Study
KW - Research Support, Non-U.S. Gov't
U2 - 10.1093/ndt/gfm501
DO - 10.1093/ndt/gfm501
M3 - Journal article
C2 - 17704113
SN - 0931-0509
VL - 23
SP - 161
EP - 168
JO - Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association
JF - Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association
IS - 1
ER -