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Clinical Chemistry and Laboratory Medicine (CCLM)

Published in Association with the European Federation of Clinical Chemistry and Laboratory Medicine (EFLM)

Editor-in-Chief: Plebani, Mario

Ed. by Gillery, Philippe / Lackner, Karl J. / Lippi, Giuseppe / Melichar, Bohuslav / Payne, Deborah A. / Schlattmann, Peter / Tate, Jillian R.

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The −374A allele of the receptor for advanced glycation end products (RAGE) gene promoter is a protective factor against cardiovascular lesions in type 2 diabetes mellitus patients

Geraldo Picheth1 / Costantino O. Costantini2 / Fábio O. Pedrosa3 / Tania Leme da Rocha Martinez4 / Emanuel Maltempi de Souza5

1Department of Biochemistry and Molecular Biology, Federal University of Paraná, Curitiba, Brazil

2Hospital Cardiológico Costantini, Curitiba, Brazil

3Department of Biochemistry and Molecular Biology, Federal University of Paraná, Curitiba, Brazil

4InCor-São Paulo University, São Paulo, Brazil

5Department of Biochemistry and Molecular Biology, Federal University of Paraná, Curitiba, Brazil

Corresponding author: Geraldo Picheth, Department of Biochemistry and Molecular Biology, Federal University of Paraná, P.O. Box 19046, 81531-990 Curitiba, PR, Brazil Phone/Fax: +55-41-3274-5593, ,

Citation Information: Clinical Chemical Laboratory Medicine. Volume 45, Issue 10, Pages 1268–1272, ISSN (Online) 14374331, ISSN (Print) 14346621, DOI: 10.1515/CCLM.2007.273, October 2007

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Background: Polymorphisms of the receptor for advanced glycation end products (RAGE) gene have been associated with diabetes, coronary artery disease (CAD) and inflammatory processes. The –374T>A RAGE gene promoter polymorphism was shown to affect gene transcription. The aim of this study was to evaluate the association of the –374T>A polymorphism with the severity of CAD in patients with or without type 2 diabetes mellitus.

Methods: We studied 246 Euro-Brazilians with angiographically defined CAD (stenosis >50%), comprising type 2 diabetic (n=98) and non-diabetic subjects (n=148). Genotyping was performed by PCR-restriction fragment length polymorphism using Tsp509I restriction enzyme.

Results: The AA genotype was associated with a significant decrease in CAD severity estimated by the number of diseased vessels (1.43±0.5 vs. 2.49±1.1; p=0.002) and the Duke score (27.3±10.8 vs. 49.3±20.1; p=0.001) only in the group of CAD subjects with type 2 diabetes mellitus. The protective effect of the AA genotype against severity of CAD was not observed in the non-diabetic group.

Conclusion: This result confirms that the –374AA genotype of the RAGE gene promoter is a protective factor against the severity of CAD lesions in type 2 diabetic patients.

Clin Chem Lab Med 2007;45:1268–72.

Keywords: advanced glycation end products; coronary artery disease; disease severity; Euro-Brazilians; risk factor; single nucleotide polymorphism; type 2 diabetes

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