European rational approach for the genetics of diabetic complications--EURAGEDIC: patient populations and strategy.

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 EURAG...

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Main Authors: Tarnow, L, Groop, P, Hadjadj, S, Kazeem, G, Cambien, F, Marre, M, Forsblom, C, Parving, H, Trégouët, D, Thévard, A, Farrall, M, Gut, I, Gauguier, D, Cox, R, Matsuda, F, Lathrop, M, Vionnet, N
Format: Journal article
Language:English
Published: 2008
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author Tarnow, L
Groop, P
Hadjadj, S
Kazeem, G
Cambien, F
Marre, M
Forsblom, C
Parving, H
Trégouët, D
Thévard, A
Farrall, M
Gut, I
Gauguier, D
Cox, R
Matsuda, F
Lathrop, M
Vionnet, N
author_facet Tarnow, L
Groop, P
Hadjadj, S
Kazeem, G
Cambien, F
Marre, M
Forsblom, C
Parving, H
Trégouët, D
Thévard, A
Farrall, M
Gut, I
Gauguier, D
Cox, R
Matsuda, F
Lathrop, M
Vionnet, N
author_sort Tarnow, L
collection OXFORD
description 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.
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spelling oxford-uuid:c568251c-4164-4d9d-bf4e-564ccab717592022-03-27T06:30:37ZEuropean rational approach for the genetics of diabetic complications--EURAGEDIC: patient populations and strategy.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:c568251c-4164-4d9d-bf4e-564ccab71759EnglishSymplectic Elements at Oxford2008Tarnow, LGroop, PHadjadj, SKazeem, GCambien, FMarre, MForsblom, CParving, HTrégouët, DThévard, AFarrall, MGut, IGauguier, DCox, RMatsuda, FLathrop, MVionnet, NBACKGROUND: 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.
spellingShingle Tarnow, L
Groop, P
Hadjadj, S
Kazeem, G
Cambien, F
Marre, M
Forsblom, C
Parving, H
Trégouët, D
Thévard, A
Farrall, M
Gut, I
Gauguier, D
Cox, R
Matsuda, F
Lathrop, M
Vionnet, N
European rational approach for the genetics of diabetic complications--EURAGEDIC: patient populations and strategy.
title European rational approach for the genetics of diabetic complications--EURAGEDIC: patient populations and strategy.
title_full European rational approach for the genetics of diabetic complications--EURAGEDIC: patient populations and strategy.
title_fullStr European rational approach for the genetics of diabetic complications--EURAGEDIC: patient populations and strategy.
title_full_unstemmed European rational approach for the genetics of diabetic complications--EURAGEDIC: patient populations and strategy.
title_short European rational approach for the genetics of diabetic complications--EURAGEDIC: patient populations and strategy.
title_sort european rational approach for the genetics of diabetic complications euragedic patient populations and strategy
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