AIM: The chemokine fractalikine is expressed in vascular endothelium, exerting a pro-atherogenic effect. Two single-nucleotide polymorphisms of the CX3CR1 gene (T280M and V249I) affect frac-talkine receptor expression and function. We aimed to assess the prevalence of CX3CR1 polymor-phisms and the association with ischemic cerebrovascular attacks in a cohort of carotid atheromatous disease patients and age-matched controls.METHODS: Using PCR-RFLP, we analyzed allelotypes for T280M and V249I in 150 patients with and 151 controls without carotid atherosclerosis assessed using carotid duplex ultrasound; the subjects were patients admitted for any reason to a tertiary hospital. Genotype data were compared with modifiable risk factors for cerebrovascular disease and the reason for admission, using ischemic stroke as an endpoint. Stroke types associated with carotid atherosclerosis were analysed separately.RESULTS: The M280 allelic frequency was lower among carotid atherosclerosis patients than controls (0.15 versus 0.23, adjusted OR 0.47, 95% CI 0.30-0.74). Absence of M280 allele was an indepen-dent factor associated with carotid atherosclerosis (OR 3.70, 95% CI 1.92-7.14), stronger than hypertension, dyslipidemia, diabetes and cigarette smoking. The I249 allele was also under-repre-sented in carotid atherosclerosis; this was not statistically significant. T280M and V249I genotypes were not associated with admission due to ischemic stroke of the large vessel subtype (TOAST classi-fication, 73 episodes), whereas carotid atherosclerosis, previous ischemic event, age, hypertension, diabetes, hyperlipidemia and cigarette smoking were all independently associated.CONCLUSIONS: The M280 fractalkine receptor gene allele is associated with a lower risk of carotid ath-eromatous disease, independent from the modifiable cerebrovascular risk factors.