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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2005;25:847.)
© 2005 American Heart Association, Inc.

Atherosclerosis & Lipoproteins

Adverse Associations Between CX3CR1 Polymorphisms and Risk of Cardiovascular or Cerebrovascular Disease

Elise Lavergne; Julien Labreuche; Mehdi Daoudi; Patrice Debré; François Cambien; Philippe Deterre; Pierre Amarenco; Christophe Combadière on Behalf of the GENIC Investigators

From Laboratoire d’Immunologie Cellulaire, INSERM U543 (E.L., M.D., P. Debré, P. Deterre, C.C.) and the INSERM U525 (F.C.), Hôpital Pitié-Salpêtrière, Paris, France; and the Service de Neurologie (J.L., P.A.), CHU Bichat, Paris, France.

Correspondence to Christophe Combadière, INSERM U543, Laboratoire d’Immunologie Cellulaire, Hôpital Pitié-Salpêtrière, 91 Boulevard de l’Hôpital, 75654 Paris, cedex 13, France. E-mail combad{at}ccr.jussieu.fr

Objective— We investigated the role of monocyte-recruiting chemokines in cerebrovascular diseases among the subjects of the GENIC case-control study of brain infarction (BI).

Methods and Results— Of the genotypes tested, only homozygosity for the rare CX3CR1 alleles was more frequent in cases than in controls: the I249 and M280 alleles were associated with an increased risk of BI (OR, 1.66 and OR, 2.62 with P<0.05, respectively). This effect was independent of other established risk factors and uncorrelated with disease severity. The study confirmed previous reports of a dominant protective association between CX3CR1-I249 allele and the risk of cardiovascular history. The risk of BI associated with homozygosity for the rare CX3CR1 alleles was enhanced in patients with no previous cardiovascular events. Ex vivo studies showed that the number of monocytes adhering to immobilized CX3CL1, the CX3CR1 ligand, increased proportionally to the number of CX3CR1 mutated alleles carried by the individual.

Conclusions— The rare CX3CR1 alleles were associated with an increased risk of BI and with reduced frequency of cardiovascular history. We propose that the extra adhesion of monocytes observed in individuals carrying rare alleles of CX3CR1 may favor mechanisms leading to stroke.

We analyzed the role of monocyte-recruiting chemokines in cerebrovascular diseases among the subjects of a case-control study of brain infarction (BI). Of the alleles tested, only homozygosity for the CX3CR1 rare alleles was associated with increased risk of BI. The associations may be related to CX3CL1-mediated monocyte adhesion.

Key Words: cerebral infarction • genetics • leukocytes • chemokines • inflammation • risk factors

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