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European Heart Journal 2004 25(16):1438-1446; doi:10.1016/j.ehj.2004.05.005
Copyright © 2004 by the European Society of Cardiology.
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Clinical research

Association of RANTES G-403A gene polymorphism with increased risk of coronary arteriosclerosis

Eleonora Simeonia,b,1, Bernhard R. Winkelmannc,1, Michael M. Hoffmannd,1, Sylvain Fleurya,b, Juan Ruize, Lukas Kappenbergera, Winfried Märzf and Giuseppe Vassallia,g,*

a Division of Cardiology, University of Lausanne Medical School, CHUV-BH-10, 1011 Lausanne, Switzerland
b Experimental Surgery, University of Lausanne Medical School, Lausanne, Switzerland
c The Cooperation Unit Pharmacogenomics/Applied Genomics, University of Heidelberg, Heidelberg, Germany
d The Department of Clinical Chemistry, University of Freiburg, Freiburg, Germany
e Endocrinology, University of Lausanne Medical School, Lausanne, Switzerland
f The Department of Clinical Chemistry, Graz, Austria
g The Institute of Microbiology, University of Lausanne Medical School, Lausanne, Switzerland

Received November 27, 2003; revised April 30, 2004; accepted May 5, 2004 * Corresponding author. Tel.: +41-21-3140076; fax: +41-21-3140013
gvassall{at}hospvd.ch

See page 1378 for the editorial comment on this article2

Aims Polymorphisms in the RANTES (G-403A), monocyte chemoattractant protein-1 (MCP-1; A-2518G), stromal cell-derived factor-1ß (SDF-1ß; G801A), and C–C chemokine receptor-5 (CCR5; {Delta}32) genes have been associated with functional effects. These chemokines have been implicated in leucocyte recruitment to arterial lesions. In a case-control study, we explored relations between these polymorphisms and coronary artery disease (CAD), with respect to angiographic abnormalities and acute coronary syndromes (ACS).

Methods and Results The LUdwigshafen Risk and Cardiovascular health (LURIC) cohort was genotyped by RFLP-PCR. Based on coronary angiography, individuals were sub-divided into CAD cases and controls . RANTES-403 genotype frequencies were significantly different in cases and controls , as were A allele carrier frequencies (36.01% vs. 30.19%, OR=1.30 [95%-CI=1.06–1.60], ). By multivariate analysis, RANTES A-403 retained significant association with CAD . RANTES A-403 was associated with increased ACS prevalence (OR=1.36 [95%-CI=1.08–1.71], ). MCP-1 G-2518, SDF-1ß A801, and CCR5 {Delta}32 were not associated with CAD.

Conclusions RANTES A-403 was associated with CAD independently from conventional risk factors and CRP or fibrinogen as inflammatory biomarkers. The association was enhanced in smokers and ACS, conditions where platelet activation and inflammation predominate. RANTES A-403 may increase genetic susceptibility to CAD.

Key Words: RANTES • MCP-1 • SDF-1ß • CCR5 • Polymorphism • Coronary artery disease


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