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The Identification of Risk Factors for the Development of Diabetic Nephropathy: The PREDICTIONS Project

Objective

Diabetic nephropathy (DN) is one of the most severe and life-threatening complications of diabetes mellitus. About 30% of patients with type 2 diabetes will eventually develop DN. Duration of diabetes as well as glycaemicand blood pressure control do not s ufficiently explain the risk of developing DN. About 31 genes have been reported to possibly contribute to DN susceptibility. A major susceptibility gene was mapped to 18q and a sequence variant in the CNDP1 gene was identified to cause a 3-fold elevated risk of DN. On the proteomic level, protein modifications by advanced glycation end-products (AGEs) are known to be sufficient to cause DN. AGEs are closely linked to reactive oxygen species (ROS) production. Different variables promise to have the poten tial of serving as biomarkers with high predictive value for DN risk assessment. To achieve the goals of the programme calling for identification of pathophysiological relevant genes and biomarkers correlated with onset, progression and response to therapy of DN, the project focuses on prospective research and case-control studies to: - Systematically re-evaluate available genetic data - Perform functional genomics for studying effects of gene variants - Study the influence of AGEs, ROS and carnosine a nd further predictive biomarkers. The latter will be realized both on the genomic (expression profiling in kidney biopsies) and proteomic level (mass-spectometry). In 3 multivariate analyses these markers will be correlated with the success of treatment wi th ACE inhibitors, irbesartan, and benfotiamine. A risk model will be developed for use by clinicians, who will evaluate the model prospectively in the future. This proposal will have significant impact on patient care. It is expected to provide scientif ic evidence for novel individualized therapeutic approaches. Although there is a focus on DN, the effects of DN-related markers on retinopathy will also be studied.

Call for proposal

FP6-2004-LIFESCIHEALTH-5
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Funding Scheme

STREP - Specific Targeted Research Project

Coordinator

RUPRECHT-KARLS UNIVERSITY HEIDELBERG
Address
Im Neuenheimer Feld 672
Heidelberg
Germany

Participants (9)

UNIVERSITAET GRAZ
Austria
Address
Universitätsplatz 3
Graz
LEIDEN UNIVERSITY MEDICAL CENTER
Netherlands
Address
Albinusdreef 2, 2333 Za Leiden
Leiden
UNIVERSITY MEDICAL CENTER GRONINGEN
Netherlands
Address
Hanzeplein 1
Groningen
UNIVERSITY OF ESSEX
United Kingdom
Address
Wivenhoe Park
Colchester
CHARLES UNIVERSITY, 3RD FACULTY OF MEDICINE
Czechia
Address
Ruská 87
Prague 10
NOVO NORDISK (STENO DIABETES CENTER)
Denmark
Address
Niels Steensens Vei 2
Gentofte
MOSAIQUES DIAGNOSTICS GMBH
Germany
Address
Mellendorfer Str. 7-9
Hannover
WOERWAG PHARMA GMBH & CO KG
Germany
Address
Calwer Strasse 7
Boeblingen
UNIVERSITY OF WARWICK
United Kingdom
Address
Kirby Corner Road
Coventry