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Title: RANTES/CCL5 and risk for coronary events: Results from the MONICA/KORA Augsburg case-cohort, Athero-express and CARDIoGRAM studies
Authors: Kathiresan, S.
Reilly, M. P.
Samani, Nilesh Jayantilal
Schunkert, H.
Erdmann, J.
Assimes, T. L.
Boerwinkle, E.
Hall, A.
Hengstenberg, C.
König, I. R.
Laaksonen, R.
McPherson, R.
Thompson, J. R.
Thorsteinsdottir, U.
Ziegler, A.
Absher, D.
Chen, L.
Cupples, L. A.
Halperin, E.
Li, M.
Musunuru, K.
Preuss, M.
Schillert, A.
Thorleifsson, G.
Voight, B. F.
Wells, G. A.
Deloukas, P.
Holm, H.
Roberts, R.
Stewart, A. F. R.
Fortmann, S.
Go, A.
Hlatky, M.
Iribarren, C.
Knowles, J.
Myers, R.
Quertermous, T.
Sidney, S.
Risch, N.
Tang, H.
Blankenberg, S.
Zeller, T.
Wild, P.
Schnabel, R.
Sinning, C.
Lackner, K.
Tiret, L.
Nicaud, V.
Cambien, F.
Bickel, C.
Rupprecht, H. J.
Perret, C.
Proust, C.
Münzel, T.
Barbalic, M.
Bis, J.
Chen, I. Y. D.
Dehghan, A.
Demissie-Banjaw, S.
Folsom, A.
Glazer, N.
Gudnason, V.
Harris, T.
Heckbert, S.
Levy, D.
Lumley, T.
Marciante, K.
Morrison, A.
O'Donnell, C. J.
Psaty, B. M.
Rice, K.
Rotter, J. I.
Siscovick, D. S.
Smith, N.
Smith, A.
Taylor, K. D.
van Duijn, C.
Volcik, K.
Whitteman, J.
Ramachandran, V.
Hofman, A.
Uitterlinden, A.
Gretarsdottir, S.
Gulcher, J. R.
Kong, A.
Stefansson, K.
Thorgeirsson, G.
Andersen, K.
Fischer, M.
Grosshennig, A.
Lieb, W.
Linsel-Nitschke, P.
Stark, K.
Schreiber, S.
Wichmann, H-E.
Aherrahrou, Z.
Bruse, P.
Doering, A.
Illig, T.
Klopp, N.
Loley, C.
Medack, A.
Meisinger, C.
Meitinger, T.
Nahrstedt, J.
Peters, A.
Wagner, A. K.
Willenborg, C.
Böhm, B. O.
Dobnig, H.
Grammer, T. B.
Hoffmann, M. M.
Kleber, M.
März, W.
Meinitzer, A.
Winkelmann, B. R.
Pilz, S.
Renner, W.
Scharnagl, H.
Stojakovic, T.
Tomaschitz, A.
Winkler, K.
Guiducci, C.
Burtt, N.
Gabriel, S. B.
Elosua, R.
Peltonen, L.
Salomaa, V.
Schwartz, S. M.
Melander, O.
Altshuler, D.
Dandona, S.
Jarinova, O.
Qu, L.
Wilensky, R.
Matthai, W.
Hakonarson, H. H.
Devaney, J.
Burnett, M. S.
Pichard, A. D.
Kent, K. M.
Satler, L.
Lindsay, J. M.
Waksman, R.
Knouff, C. W.
Waterworth, D. M.
Walker, M. C.
Mooser, V.
Epstein, S. E.
Rader, D. J.
Braund, P. S.
Nelson, C. P.
Wright, B. J.
Balmforth, A. J.
Ball, S. G.
First Published: 6-Dec-2011
Publisher: Public Library of Science
Citation: PLoS ONE, 2011, 6 (12), e25734
Abstract: Background: The chemokine RANTES (regulated on activation, normal T-cell expressed and secreted)/CCL5 is involved in the pathogenesis of cardiovascular disease in mice, whereas less is known in humans. We hypothesised that its relevance for atherosclerosis should be reflected by associations between CCL5 gene variants, RANTES serum concentrations and protein levels in atherosclerotic plaques and risk for coronary events. Methods and Findings: We conducted a case-cohort study within the population-based MONICA/KORA Augsburg studies. Baseline RANTES serum levels were measured in 363 individuals with incident coronary events and 1,908 non-cases (mean follow-up: 10.2±4.8 years). Cox proportional hazard models adjusting for age, sex, body mass index, metabolic factors and lifestyle factors revealed no significant association between RANTES and incident coronary events (HR [95% CI] for increasing RANTES tertiles 1.0, 1.03 [0.75-1.42] and 1.11 [0.81-1.54]). None of six CCL5 single nucleotide polymorphisms and no common haplotype showed significant associations with coronary events. Also in the CARDIoGRAM study (>22,000 cases, >60,000 controls), none of these CCL5 SNPs was significantly associated with coronary artery disease. In the prospective Athero-Express biobank study, RANTES plaque levels were measured in 606 atherosclerotic lesions from patients who underwent carotid endarterectomy. RANTES content in atherosclerotic plaques was positively associated with macrophage infiltration and inversely associated with plaque calcification. However, there was no significant association between RANTES content in plaques and risk for coronary events (mean follow-up 2.8±0.8 years). Conclusions: High RANTES plaque levels were associated with an unstable plaque phenotype. However, the absence of associations between (i) RANTES serum levels, (ii) CCL5 genotypes and (iii) RANTES content in carotid plaques and either coronary artery disease or incident coronary events in our cohorts suggests that RANTES may not be a novel coronary risk biomarker. However, the potential relevance of RANTES levels in platelet-poor plasma needs to be investigated in further studies. © 2011 Herder et al.
DOI Link: 10.1371/journal.pone.0025734
eISSN: 1932-6203
Version: Publisher Version
Status: Peer-reviewed
Type: Journal Article
Rights: Copyright © 2011 Herder et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Appears in Collections:Published Articles, Dept. of Health Sciences
Published Articles, Dept. of Cardiovascular Sciences

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