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Association of the CCR5 Δ32 variant with juvenile idiopathic arthritis in a meta-analysis
Pediatric Rheumatology volume 9, Article number: P287 (2011)
Background
CCR5 is expressed on Th1 cells and may play a role in Rheumatoid Arthritis by recruiting these cells to the synovium, where they drive an inflammatory process. The CCR5 Δ32 variant, a deletion variant which leads to a dysfunctional receptor, has been reported in several genetic association studies in Juvenile Idiopathic Arthritis (JIA), with conflicting results. CCL14 is one of the ligands of CCR5 and polymorphisms in the CCL14 gene have been reported to be associated with Systemic Lupus Erythematosus.
Aim
We performed a case-control genetic association study to investigate whether CCR5 and CCL14 polymorphisms are associated with susceptibility to JIA.
Methods
CCR5 Δ32 and CCL14 rs16971802 were genotyped in 667 JIA cases and 1320 healthy controls, both of North-West-European white origin. Patients with oligoarticular (persistent and extended), polyarticular (rheumatoid factor negative and positive) and systemic JIA have been included. A meta-analysis combined with three published studies on CCR5 Δ32 in JIA, with comparable allele frequencies in controls, was performed.
Results
CCR5 Δ32 and CCL14 rs16971802 were not significantly associated with JIA in this study, with p-values of 0.12 and 0.72 respectively. Nevertheless, meta-analysis demonstrated association of CCR5 Δ32 with protection to JIA (combined p=0.0003, OR=0.83, 95% CI: 0.75-0.91, Breslow-Day p=0.87, heterogeneity I-squared=0.0%).
Conclusion
This study has not demonstrated significant associations of CCR5 and CCL14 polymorphisms with JIA, but the association of CCR5 Δ32 with protection from developing JIA is strengthened in a meta-analysis. It is hypothesized that function of CCR5 could influence synovial inflammation also in JIA.
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This article is published under license to BioMed Central Ltd. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
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Reinards, T., Albers, H., Brinkman, D. et al. Association of the CCR5 Δ32 variant with juvenile idiopathic arthritis in a meta-analysis. Pediatr Rheumatol 9 (Suppl 1), P287 (2011). https://doi.org/10.1186/1546-0096-9-S1-P287
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DOI: https://doi.org/10.1186/1546-0096-9-S1-P287