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

G. Rudofsky; B. Isermann; T. Schilling; S. Schiekofer; M. Andrassy; J. G. Schneider; M. Morcos; P. M. Humpert; A. A. R. Sayed; S. Witte; W. Renn; M. Pfohl; A. Hamann; V. Nosikov; E. Schleicher; H.-U. Häring; E. Ritz; P. P. Nawroth; A. Bierhaus

doi:10.1055/s-2004-817822

Experimental and Clinical Endocrinology & Diabetes, Table of Contents

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

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

Full Text

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PhD Angelika Bierhaus

Department of Medicine I, University of Heidelberg

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