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Erschienen in: Acta Diabetologica 6/2013

01.12.2013 | Original Article

CD2AP is associated with end-stage renal disease in patients with type 1 diabetes

verfasst von: Mervi E. Hyvönen, Pekka Ihalmo, Niina Sandholm, Monica Stavarachi, Carol Forsblom, Amy Jayne McKnight, Maria Lajer, Anna Maestroni, Gareth Lewis, Lise Tarnow, Silvia Maestroni, Gianpaolo Zerbini, Hans-Henrik Parving, Alexander P. Maxwell, Per-Henrik Groop, Sanna Lehtonen

Erschienen in: Acta Diabetologica | Ausgabe 6/2013

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Abstract

CD2-associated protein (CD2AP) is essential for podocyte function. CD2AP mutations have been found in patients with focal segmental glomerulosclerosis, a disease histologically resembling diabetic nephropathy and often progressing to end-stage renal disease (ESRD). We hypothesised that variations in the CD2AP gene may contribute to susceptibility to glomerular injury in diabetes and investigated if single-nucleotide polymorphisms (SNPs) in CD2AP are associated with diabetic nephropathy in patients with type 1 diabetes. The discovery cohort consisted of 2,251 Finnish patients with type 1 diabetes. SNPs were selected from the HapMap database to cover the CD2AP gene. The associations between genotyped SNPs and diabetic nephropathy or ESRD were analysed with the chi-squared test and logistic regression. Three SNPs were selected for replication in cohorts from Denmark, Italy, the United Kingdom and Ireland. None of the 15 successfully genotyped SNPs were associated with diabetic nephropathy when compared to patients with normal albumin excretion rate. However, when genotype frequencies in patients with ESRD were compared with all other patients, two CD2AP SNPs, rs9369717 and rs9349417, were found to be associated with ESRD. The meta-analysis of the original and two additional European cohorts resulted in significant p values <0.01 for these SNPs. A third SNP, rs6936632, was suggestively associated with ESRD in the Finnish patients and in the meta-analysis of four cohorts. CD2AP gene variants may contribute to susceptibility to ESRD in patients with type 1 diabetes.
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Metadaten
Titel
CD2AP is associated with end-stage renal disease in patients with type 1 diabetes
verfasst von
Mervi E. Hyvönen
Pekka Ihalmo
Niina Sandholm
Monica Stavarachi
Carol Forsblom
Amy Jayne McKnight
Maria Lajer
Anna Maestroni
Gareth Lewis
Lise Tarnow
Silvia Maestroni
Gianpaolo Zerbini
Hans-Henrik Parving
Alexander P. Maxwell
Per-Henrik Groop
Sanna Lehtonen
Publikationsdatum
01.12.2013
Verlag
Springer Milan
Erschienen in
Acta Diabetologica / Ausgabe 6/2013
Print ISSN: 0940-5429
Elektronische ISSN: 1432-5233
DOI
https://doi.org/10.1007/s00592-013-0475-9

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