Journal
GENES AND IMMUNITY
Volume 11, Issue 7, Pages 584-589Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/gene.2010.25
Keywords
CCR5; juvenile idiopathic arthritis; chemokine
Categories
Funding
- Arthritis Research UK [17552]
- Medical Research Council [G0000934]
- Wellcome Trust [068545/Z/02]
- NIHR Manchester Biomedical Research Council
- MRC [G0000934] Funding Source: UKRI
- Medical Research Council [G0000934] Funding Source: researchfish
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The CC chemokine receptor 5 (CCR5) has been shown to be important in the recruitment of T-helper cells to the synovium, where they accumulate, drive the inflammatory process and the consequent synovitis and joint destruction. A 32 base-pair insertion/deletion variant (CCR5 Delta 32) within the gene leads to a frame shift and a nonfunctional receptor. CCR5 Delta 32 has been investigated for its association with juvenile idiopathic arthritis (JIA), with conflicting results. The aim of this study was to investigate whether CCR5 Delta 32 is associated with JIA in an UK population. CCR5 Delta 32 was genotyped in JIA cases (n=1054) and healthy controls (n=3129) and genotype and allele frequencies were compared. A meta-analysis of our study combined with previously published studies was performed. CCR5 Delta 32 was significantly associated with protection from developing JIA, in this UK data set (P(trend)=0.006, odds ratio (OR) 0.79 95% confidence interval (95% CI): 0.66-0.94). The meta-analysis of all published case-control association studies confirmed the protective association with JIA (P=0.001 OR 0.82 95% CI: 0.73-0.93). CCR5 Delta 32 is a functional variant determining the number of receptors on the surface of T cells, and it is hypothesized that the level of CCR5 expression could influence the migration of proinflammatory T cells into the synovium and thus susceptibility to JIA. Genes and Immunity (2010) 11, 584-589; doi:10.1038/gene.2010.25; published online 13 May 2010
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