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A CX₃CR1 Genotype Associated with Retinal Vasculitis in Patients in the United Kingdom

¹From the Departments of Ophthalmology and ³Clinical Transplantation Laboratory, Guy’s, King’s and St. Thomas’ Hospital Medical Schools, London, United Kingdom; and the ²Academic Unit of Ophthalmology, University of Birmingham, Birmingham, United Kingdom.

PURPOSE. To investigate whether polymorphisms in the gene encoding the chemokine receptor CX₃CR1, which has been linked to changes in functional ligand-binding activity, are associated with retinal vasculitis (RV) in a cohort of patients in the United Kingdom.

METHODS. DNA was prepared from whole blood of 126 patients with RV and 95 healthy individuals by a standard salting-out procedure. Two polymorphisms, V249I and T280M, were analyzed by multiplex polymerase chain reaction–sequence-specific primers (PCR-SSPs).

RESULTS. There was no significant difference between the prevalence of V249 or I249 variants in patients with RV or in control subjects. By contrast, the 280M variant was significantly raised in patients compared with control subjects (P = 0.01), the IV/MT haplotype was also more prevalent in patients with RV than in control subjects (P = 0.006), and the I249/M280 haplotype was associated with retinal vasculitis (P = 0.01). The 280M variant was significantly associated with the nonischemic form of RV compared with healthy control subjects (P = 0.009).

CONCLUSIONS. Polymorphisms related to a functional decrease in ligand binding activity of CX₃CR1 are associated with disease in U.K. patients with retinal vasculitis. CX₃CR1 and its ligand CX₃CL1 have been implicated in leukocyte adhesion and neuronal protection. Changes in the activity of this interaction may have a role in the pathogenesis of RV.

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