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Exp Clin Endocrinol Diabetes 2004; 112(3): 135-141
DOI: 10.1055/s-2004-817822
Article

J. A. Barth Verlag in Georg Thieme Verlag Stuttgart · New York

A 63bp Deletion in the Promoter of RAGE Correlates with a Decreased Risk for Nephropathy in Patients with Type 2 Diabetes

G. Rudofsky1  Jr. , B. Isermann1 , T. Schilling1 , S. Schiekofer1 , M. Andrassy1 , J. G. Schneider1 , M. Morcos1 , P. M. Humpert1 , A. A. R. Sayed1 , S. Witte2 , W. Renn3 , M. Pfohl4 , A. Hamann1 , V. Nosikov5 , E. Schleicher3 , H.-U. Häring3 , G. Rudofsky6  sen. , E. Ritz1 , P. P. Nawroth1 , A. Bierhaus1
  • 1Department of Medicine I, Otto-Meyerhof-Zentrum and Department of Nephrology, University of Heidelberg, Germany
  • 2Department of Medical Biometry, University of Heidelberg, Germany
  • 3Department of Medicine IV, University Tübingen, Germany
  • 4Medizinische Klinik I, Bethesda Kliniken zu Duisburg, Duisburg, Germany
  • 5Department of Molecular Diagnostics and Genome Fingerprinting, National Research Center “GosNIIgenetics”, Moscow, Russia
  • 6Department of Angiology, University of Essen, Germany
Further Information

Publication History

Received: April 7, 2003 First decision: May 23, 2003

Accepted: July 14, 2003

Publication Date:
30 March 2004 (online)

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Abstract

Several polymorphisms have been identified in the RAGE-promoter region that might modulate the outcome of disease. Here we analyse the association of a 63bp deletion (delta63) spanning from bp - 407 to bp - 345 with diabetic nephropathy.

The deletion was determined using the polymerase chain reaction (PCR) in a cross-sectional study with 1087 patients with type 1 diabetes (n = 559) and type 2 diabetes (n = 528). 475 patients with osteoporosis served as disease independent control.

The prevalence of the heterozygous genotype did not significantly differ between the three groups (type 1: 2.15 %, type 2: 2.27 %, controls: 1.47 %), indicating that heterozygous delta63 is not related to the manifestation of diabetes. Homozygous carriers were not identified in this study. The heterozygous delta63 genotype, was associated with a reduced prevalence of diabetic nephropathy in patients with type 2 diabetes (OR = 0.06; 95 % CI: [0.05, 0.07]), but not in patients with type 1 (OR = 1.49; 95 % CI: [1.14, 1.94]).

We conclude, that patients with type 2 diabetes and the 63bp deletion in the promoter of RAGE seem to be protected from diabetic nephropathy. The observed difference between type 1 and type 2 diabetes might point to diverse pathomechanisms of nephropathy in both types of diabetes.

Key words

Diabetes mellitus - diabetic nephropathy - receptor of advanced glycation endproducts - polymorphism

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PhD Angelika Bierhaus

Department of Medicine I, University of Heidelberg

Im Neuenheimer Feld 350

69120 Heidelberg

Germany

Phone: + 496221564752

Fax: + 49 62 21 56 47 54

Email: angelika_bierhaus@med.uni-heidelberg.de