Published Online
on April 29, 2004

A more recent version of this article appeared on June 1, 2004

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Submitted on September 17, 2003
Revised on March 4, 2004
Accepted on March 9, 2004

Internal Carotid Artery Occlusive Disease and Polymorphisms of Fractalkine Receptor CX3CR1: A Genetic Risk Factor

Giorgio Ghilardi MD^*; Maria Luisa Biondi MD; Olivia Turri PhD; Emma Guagnellini MD; and Roberto Scorza MD

From Dipartimento MCO (G.G., R.S.), Clinica Chirurgica Generale, Università degli Studi di Milano, Polo S. Paolo, Milano, Italia; and Laboratorio di Chimica Clinica e Microbiologia (M.L.B., O.T., E.G.), Ospedale S. Paolo, Polo Universitario, Milano, Italia.

^* To whom correspondence should be addressed. E-mail: giorgio.ghilardi{at}unimi.it.

Background and Purpose--Fractalkine (FKN), a chemokine expressed by inflamed endothelium, induces leukocyte adhesion and migration via the receptor CX3CR1. The polymorphisms V249I and T280M affect receptor expression and function. The role of FKN in atherosclerosis has been recently demonstrated. The aim of this study was to investigate a possible association between CX3CR1 polymorphisms and increased risk of internal carotid artery (ICA) occlusive disease.

Methods--We studied 108 patients consecutively recruited for ICA occlusive disease, 84 of whom underwent operation for carotid endarterectomy, and 204 subjects without ICA occlusive disease (controls). Polymorphic genotypes were determined by polymerase chain reaction and sequencing analysis.

Results--The adjusted odds ratio (OR) associated with the presence of the M280 (TM+MM versus TT genotype) was 0.55 (95% confidence interval [CI]: 0.29 to 0.99; P=0.037). Therefore, this allele is associated with a reduced risk of ICA occlusive disease. No significant differences were observed in I249 distribution. The frequency of I249 allele was significantly higher in cases of hard plaques, which are considered more stable than soft ones (OR: 0.38; 95% CI: 0.13 to 1.05; P=0.037). Multiple logistic regression analysis using the common risk factors and the I249 and M280 allele variants revealed that the M280 allele was an independent risk factor for ICA stenosis (P=0.047).

Conclusion--The results show that the CX3CR1 M280 is an independent genetic risk factor for ICA occlusive disease and that I249 is involved in the stability of carotid plaques. Even if obtained from a relatively limited patient series, these results might have relevant implications for treatment of ICA stenosis and possibly prevention of carotid related stroke. Further prospective cross-sectional studies are needed to confirm these results.

Key words: carotid stenosis • carotid endarterectomy • chemokines, CX3C • receptors, chemokine • polymorphisms, single nucleotide

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