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Association of rheumatoid arthritis with a functional chemokine receptor, CCR5
J J Gómez-Reino1, J L Pablos, P E Carreira
1Hospital Universitario 12 de Octubre, Madrid, Spain.
Objective:
To investigate whether the pathogenesis of rheumatoid arthritis (RA) is associated with the functional chemokine receptor CCR5, which is the primary CC chemokine receptor expressed by T cells in rheumatoid synovium, and its nonfunctional receptor, delta32CCR5, which is generated by the homozygous 32-basepair deletion (delta32) 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 control subjects. The CCR5 genotype was studied by polymerase chain reaction amplification of the region flanking the delta32 deletion (delta32CCR5).
Results:
Frequencies of the wild-type CCR5 alleles (0.929, 0.907, and 0.942, respectively) and delta32CCR5 alleles (0.071, 0.093, and 0.058, respectively) in controls, SLE patients, and RA patients did not differ significantly. However, none of the RA patients had the homozygous delta32CCR5 genotype, compared with a frequency of 0.009 in controls (P = 0.014 by Fisher's exact test; chi2 = 4.12 with Yates' correction, P = 0.042) and 0.027 in SLE patients (P = 0.003 by Fisher's exact test; chi2 = 11.63 with Yates' correction, P = 0.0006).
Conclusion:
The results suggest that the CCR5 receptor plays an important role in RA and may be a suitable target for therapy.