Study of CCR5 Gene polymorphism in rheumatoid arthritis

ABSTRACT

Chemokines are critical for the inflammatory process in autoimmune diseases such as rheumatoid arthritis [RA]. The chemokine receptor-5 [CCR5] mediates chemotaxis by CC chemokines and is expressed by lymphocytes with the phenotype and monocyte/macrophages. A 32bp deletion in the CCR5 [CCR5-delta 32 allele] abolishes receptor expression in homozygotes, while CCR5-delta 32 carriers express less receptor level than wild type homozygotes. This polymorphism is related to resistance to HIV-1 infection and progression to AIDS. It is hypothesized that CCR5-delta 32 allele may modulate the inflammatory response involved in rheumatoid arthritis and therefore may affect disease severity, susceptibility or both. In the present study 70 rheumatoid arthritis patients and 40 healthy individuals were genotyped. The frequency of CCR5-delta 32 allele was significantly higher in healthy individuals compared to rheumatoid arthritis patients [45% Vs 17%] respectively [p.value 0.033]. Homozygous delta 32 mutation was not detected in patients or controls No significant difference was found between CCR5-delta 32 carriers and wild type homozygotes regarding clinical or laboratory findings except for the tender joint count and rheumatoid factor positivity which was higher in wild type homozygotes [p.value 0.046 and 0.007 respectively]. Our data suggest that CCR5-dlta 32 carriers may partially protected against rheumatoid arthritis, and suggest CCR5 receptor as a candidate for targeted therapy in rheumatoid arthritis