Neuroscience Letters 374 (2005) 132–135 T280M and V249I polymorphisms of fractalkine receptor CX3CR1 and ischemic cerebrovascular disease Hidenori Hattori a,∗ , Daisuke Ito a , Norio Tanahashi a , Mitsuru Murata b , Ikuo Saito c , Kiyoaki Watanabe d , Norihiro Suzuki a a Departments of Neurology, School of Medicine, Keio University, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan b Departments of Hematology, School of Medicine, Keio University, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan c The Health Center, School of Medicine, Keio University, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan d Laboratory Medicine, School of Medicine, Keio University, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan Received 14 September 2004; received in revised form 13 October 2004; accepted 14 October 2004 Abstract The contribution to atherosclerosis of two CX3CR1 single nucleotide polymorphisms, V249I and T280M has been recently reported. The atherosclerosis of intracranial vessels is thought to be the major pathological mechanism of ischemic stroke. In this study, we investigated the risk of ischemic stroke associated with fractalkine receptor CX3CR1 polymorphisms. We investigated the T280M and V249I mutations in the CX3CR1 gene in 235 Japanese patients with ischemic cerebrovascular disease (CVD) and 306 age- and sex-matched healthy controls. Polymerase chain reaction and restriction fragment length polymorphism were used for genotyping. There was no significant difference in both polymorphisms between patients with ischemic CVD and controls (VV versus II + VI, p = 0.83; TT versus MM + TM, p = 0.66). The I and M allele frequencies were not significantly different between CVD patients and controls: odds ratio (OR) = 0.89 (95% confidence interval (CI) = 0.50–1.60, p = 0.70) and OR = 1.19 (95% CI = 0.71–2.00, p = 0.51), respectively. We found eight of nine possible combined genotypes, including a new haplotype V249-M280, in Japanese. Our results show that these CX3CR1 gene polymorphisms are not associated with an increased risk for ischemic CVD in the Japanese population. © 2004 Elsevier Ireland Ltd. All rights reserved. Keywords: Ischemic stroke; Atherosclerosis; Polymorphism; CX3CR1; Fractalkine In 2001, Moatti et al. [12] reported that the I249 allele of the CX3CR1 gene had the ability to reduce the risk of coro- nary artery disease. Two CX3CR1 single nucleotide poly- morphisms, V249I and T280M, are located in the coding sequence, and a recent study demonstrated that I249-M280 homozygotes have lower fractalkine binding affinity on pri- mary peripheral blood mononuclear cells (PBMC) compared with V249-T280 homozygotes [3]. These results prompted researchers to examine the correlation between these alleles and the pathogenesis of atherosclerotic disease. ∗ Corresponding author. Tel.: +81 3 5363 3788; fax: +81 3 3353 1272. E-mail address: hhattori@sc.itc.keio.ac.jp (H. Hattori). Imai et al. [7] identified a novel seven-transmembrane receptor for fractalkine, which is expressed mainly on NK cells and monocytes, and partly on T cells, and named it CX3CR1. Fractalkine, a CX3C motif protein, is a transmem- brane, mucin/chemokine hybrid molecule, which is induced on activated primary endothelial cells [1]. Fractalkine is cap- tured on the cell surface of inflammatory factor-activated leukocytes, so interaction between fractalkine and CX3CR1 may contribute to atherogenesis, which consists of inflam- mation, adhesion between leukocytes and the endothelium, and leukocyte migration into the endothelium [4]. Some studies have examined the correlation between these polymorphisms and atherosclerotic disease, but no study has focused on the association between these polymorphisms 0304-3940/$ – see front matter © 2004 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.neulet.2004.10.042