Internal Carotid Artery Occlusive Disease and Polymorphisms of Fractalkine Receptor CX3CR1
- 1 June 2004
- journal article
- research article
- Published by Wolters Kluwer Health in Stroke
- Vol. 35 (6) , 1276-1279
Abstract
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% 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.Keywords
This publication has 17 references indexed in Scilit:
- Overview of the principal results and secondary analyses from the European and North American randomised trials of endarterectomy for symptomatic carotid stenosisEuropean Journal of Vascular and Endovascular Surgery, 2003
- Reanalysis of the Final Results of the European Carotid Surgery TrialStroke, 2003
- Bone Formation in Carotid PlaquesStroke, 2002
- Polymorphism in the fractalkine receptor CX3CR1 as a genetic risk factor for coronary artery diseaseBlood, 2001
- Rapid Progression to AIDS in HIV + Individuals with a Structural Variant of the Chemokine Receptor CX 3 CR1Science, 2000
- Atherosclerosis — An Inflammatory DiseaseNew England Journal of Medicine, 1999
- Randomised trial of endarterectomy for recently symptomatic carotid stenosis: final results of the MRC European Carotid Surgery Trial (ECST)The Lancet, 1998
- Endarterectomy for Asymptomatic Carotid Artery StenosisJAMA, 1995
- Risk of stroke in the distribution of an asymptomatic carotid arteryThe Lancet, 1995
- Beneficial Effect of Carotid Endarterectomy in Symptomatic Patients with High-Grade Carotid StenosisNew England Journal of Medicine, 1991