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http://purl.uniprot.org/citations/17604289http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/17604289http://www.w3.org/2000/01/rdf-schema#comment"

Objective

There is increasing evidence that gene copy-number variation influences phenotypic variation. Chemokine ligand 3-like 1 (CCL3L1) is encoded by a variable copy-number gene, and binds to several pro-inflammatory cytokine receptors, including chemokine receptor 5 (CCR5). Considering lymphocyte recruitment by beta-chemokines is a feature of autoimmunity, and that the CCR5Delta32 variant is associated with protection to rheumatoid arthritis (RA), we hypothesised that CCL3L1 copy-number influences susceptibility to RA and type 1 diabetes (T1D).

Methods

We measured CCL3L1 copy-number in 1136 RA cases from New Zealand (NZ) and the UK, 252 NZ T1D cases and a total of 1470 controls. All subjects were ancestrally Caucasian.

Results

A copy-number higher than 2 (the most common copy number) was a risk factor for RA in the NZ cohort (odds ratio (OR) 1.34, 95% CI 1.08-1.66, p = 0.009) but not the smaller UK RA cohort (OR 1.09, 95% CI 0.75-1.60, p = 0.643). There was evidence for association in the T1D cohort (OR 1.46, 95% CI 0.98-2.20, p = 0.064) and in the combined RA/T1D cohort (OR 1.30, 95% CI 1.00-1.54, p = 0.003). Genetic interaction between CCL3L1 dosage and CCR5 genotype was found; the increased genetic risk conferred by higher CCL3L1 copy-number was ablated by a dysfunctional CCR5 (CCR5Delta32).

Conclusions

These data suggest that increased CCL3L1 expression may enhance inflammatory responses and increase the chance of autoimmune disease. Genetic interaction data were consistent with a biologically plausible model; CCR5Delta32 protects against RA and T1D by blocking signalling through the CCR5 pathway, mitigating the pro-inflammatory effects of excess CCL3L1."xsd:string
http://purl.uniprot.org/citations/17604289http://purl.org/dc/terms/identifier"doi:10.1136/ard.2007.075028"xsd:string
http://purl.uniprot.org/citations/17604289http://purl.uniprot.org/core/author"Willis J."xsd:string
http://purl.uniprot.org/citations/17604289http://purl.uniprot.org/core/author"Jones P.B."xsd:string
http://purl.uniprot.org/citations/17604289http://purl.uniprot.org/core/author"Merriman M.E."xsd:string
http://purl.uniprot.org/citations/17604289http://purl.uniprot.org/core/author"Steer S."xsd:string
http://purl.uniprot.org/citations/17604289http://purl.uniprot.org/core/author"McLean L."xsd:string
http://purl.uniprot.org/citations/17604289http://purl.uniprot.org/core/author"Merriman T.R."xsd:string
http://purl.uniprot.org/citations/17604289http://purl.uniprot.org/core/author"McKinney C."xsd:string
http://purl.uniprot.org/citations/17604289http://purl.uniprot.org/core/author"Pokorny V."xsd:string
http://purl.uniprot.org/citations/17604289http://purl.uniprot.org/core/author"Gow P.J."xsd:string
http://purl.uniprot.org/citations/17604289http://purl.uniprot.org/core/author"Harrison A.A."xsd:string
http://purl.uniprot.org/citations/17604289http://purl.uniprot.org/core/author"Highton J."xsd:string
http://purl.uniprot.org/citations/17604289http://purl.uniprot.org/core/author"Chapman P.T."xsd:string
http://purl.uniprot.org/citations/17604289http://purl.uniprot.org/core/author"O'Donnell J.L."xsd:string
http://purl.uniprot.org/citations/17604289http://purl.uniprot.org/core/author"Spellerberg M."xsd:string
http://purl.uniprot.org/citations/17604289http://purl.uniprot.org/core/author"Stamp L.K."xsd:string
http://purl.uniprot.org/citations/17604289http://purl.uniprot.org/core/date"2008"xsd:gYear
http://purl.uniprot.org/citations/17604289http://purl.uniprot.org/core/name"Ann Rheum Dis"xsd:string
http://purl.uniprot.org/citations/17604289http://purl.uniprot.org/core/pages"409-413"xsd:string
http://purl.uniprot.org/citations/17604289http://purl.uniprot.org/core/title"Evidence for an influence of chemokine ligand 3-like 1 (CCL3L1) gene copy number on susceptibility to rheumatoid arthritis."xsd:string
http://purl.uniprot.org/citations/17604289http://purl.uniprot.org/core/volume"67"xsd:string
http://purl.uniprot.org/citations/17604289http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/17604289
http://purl.uniprot.org/citations/17604289http://xmlns.com/foaf/0.1/primaryTopicOfhttps://pubmed.ncbi.nlm.nih.gov/17604289
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