Association of rheumatoid arthritis with a functional chemokine receptor, CCR5

Objective. To investigate whether the pathogenesis of rheumatoid arthritis (RA) is associated,vith the functional chemokine receptor CCR5, which is th e primary CC chemokine receptor expressed by T cells in rheumatoid synovium , and its nonfunctional receptor, Delta 32CCR5, which is generated by the h omozygous 32-basepair deletion (Delta 32) in the CCR5 gene. Methods. The frequency of the CCR5 genotype was compared among 673 patients with RA, 113 patients with systemic lupus erythematosus (SLE), and 815 con trol subjects. The CCR5 genotype was studied by polymerase chain reaction a mplification of the region flanking the Delta 32 deletion (Delta 32CCR5). Results, Frequencies of the wild-type CCR5 alleles (0.929, 0.907, and 0.9-1 2, respectively) and Delta 32CCR5 alleles (0.071, 0.093, and 0.058, respect ively) in controls, SLE patients, and RA patients did not differ significan tly. However, none of the RA patients had the homozygous Delta 32CCR5 genot ype, compared with a frequency of 0.009 in controls (P = 0.014 by Fisher's exact test; chi(2) = 4.12 with Yates' correction, P = 0.042) and 0.027 in S LE patients (P = 0.003 by Fisher's exact test; chi(2) = 11.63 with Yates' c orrection, P = 0.0006). Conclusion. The results suggest that the CCR5 receptor plays an important r ole in RA and may be a suitable target for therapy.