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Association of RANTES G-403A gene polymorphism with increased risk of coronary arteriosclerosis |
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| Authors: | Simeoni, Eleonora Winkelmann, Bernhard R. Hoffmann, Michael M. Fleury, Sylvain Ruiz, Juan Kappenberger, Lukas Marz, Winfried Vassalli, Giuseppe |
| Affiliation: | 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 |
| Abstract: | Aims Polymorphisms in the RANTES (G-403A), monocyte chemoattractantprotein-1 (MCP-1; A-2518G), stromal cell-derived factor-1ß(SDF-1ß; G801A), and CC chemokine receptor-5(CCR5;  32) genes have been associated with functional effects.These chemokines have been implicated in leucocyte recruitmentto arterial lesions. In a case-control study, we explored relationsbetween these polymorphisms and coronary artery disease (CAD),with respect to angiographic abnormalities and acute coronarysyndromes (ACS). Methods and Results The LUdwigshafen Risk and Cardiovascularhealth (LURIC) cohort was genotyped by RFLP-PCR. Based on coronaryangiography, 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=1.061.60],  ). By multivariate analysis, RANTES A-403 retained significantassociation with CAD  . RANTES A-403 was associated with increased ACS prevalence (OR=1.36 [95%-CI=1.081.71], ). MCP-1 G-2518, SDF-1ß A801, and CCR5 32 were not associated with CAD. Conclusions RANTES A-403 was associated with CAD independentlyfrom conventional risk factors and CRP or fibrinogen as inflammatorybiomarkers. The association was enhanced in smokers and ACS,conditions where platelet activation and inflammation predominate.RANTES A-403 may increase genetic susceptibility to CAD. |
| Keywords: | RANTES MCP-1 SDF-1ß CCR5 Polymorphism Coronary artery disease |
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