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Related Collections Hemostasis, Thrombosis, and Vascular Biology Chemokines, Cytokines, and Interleukins Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Blood, 1 April 2001, Vol. 97, No. 7, pp. 1925-1928 CHEMOKINES Polymorphism in the fractalkine receptor CX3CR1 as a genetic risk factor for coronary artery disease Didier Moatti, Sophie Faure, Frédéric Fumeron, Mohamed El Walid Amara, Patrick Seknadji, David H. McDermott, Patrice Debré, Marie Claude Aumont, Philip M. Murphy, Dominique de Prost, and Christophe Combadière From INSERM U479, Faculté Bichat, Paris, France; CNRS UMR 7627, Laboratoire d'Immunologie Cellulaire et Tissulaire, Hôpital Pitié-Salpêtrière, Paris, France; Service de Nutrition Humaine, Faculté Bichat, Paris, France; Service de Cardiologie, CHU Bichat, Paris, France; Laboratory of Host Defenses, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA; and Service d'Hématologie Biologique et Immunologie, Hôpital Louis Mourier AP-HP, Colombes, France. Coronary atherosclerosis is a major cause of death in industrialized countries. Monocytes, which play a key role in atherosclerosis, migrate into the vessel wall, presumably guided by specific chemoattractant and adhesion molecules. A compelling candidate for this role is the chemokine receptor CX3CR1, which is expressed on monocytes and acts as either a chemotactic receptor or an adhesion molecule, depending on whether its ligand, fractalkine, is presented free or membrane bound. A common variant of CX3CR1 was recently identified, encoded by the alleles I249 and M280, which form a common I249M280 haplotype. When CX3CR1 genotypes were analyzed in 151 patients with acute coronary syndromes and in 249 healthy controls, CX3CR1 I249 heterozygosity was associated with a markedly reduced risk of acute coronary events, independent of established acquired coronary risk factors (eg, smoking, diabetes). The adjusted odds ratio for this allele was 0.43 (95% confidence interval, 0.26-0.72; P = .001). Consistent with this, functional analysis of peripheral blood mononuclear cells showed that CX3CR1 I249 heterozygosity was associated with a significant decrease in the number of fractalkine binding sites per cell. The results show that CX3CR1 I249 is an independent genetic risk factor for coronary artery disease and that CX3CR1 may be involved in the pathogenesis of atherosclerotic disease. © 2001 by The American Society of Hematology.   CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: G. E. White, T. C.C. Tan, A. E. John, C. Whatling, W. L. McPheat, and D. R. Greaves Fractalkine has anti-apoptotic and proliferative effects on human vascular smooth muscle cells via epidermal growth factor receptor signalling Cardiovasc Res, November 12, 2009; (2009) cvp341v2. [Abstract] [Full Text] [PDF] Y.-W. Huang, P. Su, G. Y. Liu, M. R. Crow, D. Chaukos, H. Yan, and L. A. Robinson Constitutive Endocytosis of the Chemokine CX3CL1 Prevents Its Degradation by Cell Surface Metalloproteases J. Biol. Chem., October 23, 2009; 284(43): 29644 - 29653. [Abstract] [Full Text] [PDF] K. Dorgham, A. Ghadiri, P. Hermand, M. Rodero, L. 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