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.
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: Marine Germain; Marcus G Pezzolesi; Niina Sandholm; Amy J McKnight; Katalin Susztak; Maria Lajer; Carol Forsblom; Michel Marre; Hans-Henrik Parving; Peter Rossing; Iiro Toppila; Jan Skupien; Ronan Roussel; Yi-An Ko; Nora Ledo; Lasse Folkersen; Mete Civelek; Alexander P Maxwell; David-Alexandre Tregouet; Per-Henrik Groop; Lise Tarnow; Samy Hadjadj Journal: Diabetologia Date: 2014-12-06 Impact factor: 10.122
Authors: Francesco Sambo; Alberto Malovini; Niina Sandholm; Monica Stavarachi; Carol Forsblom; Ville-Petteri Mäkinen; Valma Harjutsalo; Raija Lithovius; Daniel Gordin; Maija Parkkonen; Markku Saraheimo; Lena M Thorn; Nina Tolonen; Johan Wadén; Bing He; Anne-May Osterholm; Jaako Tuomilehto; Maria Lajer; Rany M Salem; Amy Jayne McKnight; Lise Tarnow; Nicolae M Panduru; Nicola Barbarini; Barbara Di Camillo; Gianna M Toffolo; Karl Tryggvason; Riccardo Bellazzi; Claudio Cobelli; Per-Henrik Groop Journal: Diabetologia Date: 2014-05-29 Impact factor: 10.122
Authors: Niina Sandholm; Carol Forsblom; Ville-Petteri Mäkinen; Amy Jayne McKnight; Anne-May Osterholm; Bing He; Valma Harjutsalo; Raija Lithovius; Daniel Gordin; Maija Parkkonen; Markku Saraheimo; Lena M Thorn; Nina Tolonen; Johan Wadén; Jaakko Tuomilehto; Maria Lajer; Emma Ahlqvist; Anna Möllsten; M Loredana Marcovecchio; Jason Cooper; David Dunger; Andrew D Paterson; Gianpaolo Zerbini; Leif Groop; Lise Tarnow; Alexander P Maxwell; Karl Tryggvason; Per-Henrik Groop Journal: Diabetologia Date: 2014-03-05 Impact factor: 10.122
Authors: A Alkhalaf; S J L Bakker; H J G Bilo; R O B Gans; G J Navis; D Postmus; C Forsblom; P H Groop; N Vionnet; S Hadjadj; M Marre; H H Parving; P Rossing; L Tarnow Journal: Diabetologia Date: 2010-08-14 Impact factor: 10.122
Authors: David-Alexandre Trégouet; Per-Henrik Groop; Steven McGinn; Carol Forsblom; Samy Hadjadj; Michel Marre; Hans-Henrik Parving; Lise Tarnow; Ralph Telgmann; Tiphaine Godefroy; Viviane Nicaud; Rachel Rousseau; Maikki Parkkonen; Anna Hoverfält; Ivo Gut; Simon Heath; Fumihiko Matsuda; Roger Cox; Gbenga Kazeem; Martin Farrall; Dominique Gauguier; Stefan-Martin Brand-Herrmann; François Cambien; Mark Lathrop; Nathalie Vionnet Journal: Diabetes Date: 2008-07-15 Impact factor: 9.461