Association of chemokine receptor CX3CR1 V249I and T280M polymorphisms with chronic kidney disease.

The chemokine fractalkine (CX3CL1) and its receptor CX3CR1 are involved in the activation of leukocytes. Two common single-nucleotide polymorphisms of the CX3CR1 gene, V249I and T280M, have been associated with reduced fractalkine signaling, leading to decreased adhesive function and leukocyte chemotaxis. We hypothesized that variation in the CX3CR1 gene could be associated with chronic kidney disease (CKD), a disease of inflammatory activation. We studied the association between CX3CR1 V249I and T280M polymorphisms, and fractalkine and highly sensitive C-reactive protein (hs-CRP) levels in 123 patients with CKD and 100 healthy controls (HCs). Genotype analysis was done by polymerase chain reaction-restriction fragment length polymorphism, and fractalkine and hs-CRP levels were analyzed by enzyme-linked immunosorbent assay. MM genotype of T280M was absent in CKD patients, while in controls it was seen in 1% of the individuals. The allele frequencies in both the groups were similar (P = 0.059). Compared to HC, M280M + T280M genotype was more frequent in CKD (P = 0.041). The frequency of II genotype of V249I was 0.8% in CKD, whereas in HC, it was 2%. I249I + V249I genotype was more frequent in CKD as compared to HC (P = 0.034). No difference in allelic frequency of V249I was noted between the two groups (P = 0.061, odds ratios = 1.74, 95% confidence intervals = 0.96-3.12). Plasma fractalkine and serum hs-CRP levels were higher in CKD subjects (P = 0.004 and P < 0.0001). No association of either genotype was found with fractalkine and hs-CRP levels. Polymorphisms at I249 and M280 genotype in CX3CR1 gene are associated with CKD; however, there was no association of fractalkine or inflammatory marker with these genotypes.