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- DOI: 10.1038/gene.2010.25
- PMID: 20463745
- UKPMCID: 20463745
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Association of the CCR5 gene with juvenile idiopathic arthritis.
Hinks, A; Martin, P; Flynn, E; Eyre, S; Packham, J; Childhood Arthritis_Prospective_Study_(CAPS); UKRAG, A; Barton, A; Worthington, J; Thomson, W
Genes Immun. 2010;11(7):584-589.
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Full-text held externally
- DOI: 10.1038/gene.2010.25
- PMID: 20463745
- UKPMCID: 20463745
Abstract
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 (CCR5Delta32) within the gene leads to a frame shift and a nonfunctional receptor. CCR5Delta32 has been investigated for its association with juvenile idiopathic arthritis (JIA), with conflicting results. The aim of this study was to investigate whether CCR5Delta32 is associated with JIA in an UK population. CCR5Delta32 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. CCR5Delta32 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). CCR5Delta32 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 advance online publication, 13 May 2010; doi:10.1038/gene.2010.25.