title: Association of the CCR5 gene with juvenile idiopathic arthritis.
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 (CCR5Δ32) within the gene leads to a frame shift and a nonfunctional receptor. CCR5Δ32 has been investigated for its association with juvenile idiopathic arthritis (JIA), with conflicting results. The aim of this study was to investigate whether CCR5Δ32 is associated with JIA in an UK population. CCR5Δ32 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. CCR5Δ32 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). CCR5Δ32 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.
authors.affiliation: Manchester Academy of Health Sciences, The University of Manchester, UK. Anne.Hinks@manchester.ac.uk
authors.forename: A
authors.initials: A
authors.lastname: Hinks
authors.forename: P
authors.initials: P
authors.lastname: Martin
authors.forename: E
authors.initials: E
authors.lastname: Flynn
authors.forename: S
authors.initials: S
authors.lastname: Eyre
authors.forename: J
authors.initials: J
authors.lastname: Packham
authors.forename: A
authors.initials: A
authors.lastname: Barton
authors.forename: J
authors.initials: J
authors.lastname: Worthington
authors.forename: W
authors.initials: W
authors.lastname: Thomson
mesh_terms: D000483:Alleles; D001171:Arthritis, Juvenile / Q000235:genetics*; D016022:Case-Control Studies; D015331:Cohort Studies; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D005838:Genotype; D006801:Humans; D008297:Male; D019713:Receptors, CCR5 / Q000235:genetics*; D017384:Sequence Deletion; D013583:Synovial Membrane / Q000166:cytology; D006377:T-Lymphocytes, Helper-Inducer / Q000166:cytology; D006113:United Kingdom
chemical_list: D019713:Receptors, CCR5
references.citation: Genes Immun. 2006 Sep;7(6):468-75
references.pmid: 16775617
references.citation: Rheumatology (Oxford). 2006 Apr;45(4):365-8
references.pmid: 16418195
references.citation: Nat Genet. 2007 Dec;39(12):1431-3
references.pmid: 17982455
references.citation: Arthritis Rheum. 2000 Apr;43(4):765-74
references.pmid: 10765921
references.citation: Genes Immun. 2000;1(4):288-9
references.pmid: 11196706
references.citation: J Biol Chem. 2002 Jan 18;277(3):2287-301
references.pmid: 11604406
references.citation: Arthritis Rheum. 1999 May;42(5):989-92
references.pmid: 10323455
references.citation: Arthritis Rheum. 2009 Jan;60(1):251-7
references.pmid: 19116909
references.citation: J Rheumatol. 1998 Aug;25(8):1462-5
references.pmid: 9712084
references.citation: Am J Hum Genet. 2007 Sep;81(3):559-75
references.pmid: 17701901
references.citation: Rheumatology (Oxford). 2002 Dec;41(12):1428-35
references.pmid: 12468825
references.citation: J Rheumatol. 2004 Feb;31(2):390-2
references.pmid: 14760812
references.citation: AIDS. 1999 Mar 11;13(4):455-63
references.pmid: 10197373
references.citation: Arthritis Rheum. 1998 Jun;41(6):1135-6
references.pmid: 9627027
references.citation: Ann Rheum Dis. 2010 Jun;69(6):1049-53
references.pmid: 19674979
references.citation: Genes Immun. 2010 Mar;11(2):194-8
references.pmid: 20072139
references.citation: Science. 1995 Dec 15;270(5243):1811-5
references.pmid: 8525373
references.citation: Nature. 1998 Jan 22;391(6665):344-5
references.pmid: 9450746
references.citation: J Immunol. 2009 Jan 1;182(1):171-82
references.pmid: 19109148
references.citation: Proc Natl Acad Sci U S A. 2003 Sep 2;100(18):10411-6
references.pmid: 12915736
references.citation: N Engl J Med. 2008 Dec 25;359(26):2767-77
references.pmid: 19073967
references.citation: Genes Immun. 2006 Apr;7(3):264-8
references.pmid: 16541097
references.citation: BMC Med Genet. 2007 Jun 12;8:33
references.pmid: 17565662
references.citation: Arthritis Res Ther. 2009;11(3):R91
references.pmid: 19538721
references.citation: Rheumatology (Oxford). 2008 Jul;47(7):991-5
references.pmid: 18417527
references.citation: J Clin Immunol. 2001 Mar;21(2):116-25
references.pmid: 11332650
references.citation: Arthritis Rheum. 2009 Mar;60(3):901-4
references.pmid: 19248117
references.citation: J Infect Dis. 2000 Mar;181(3):933-8
references.pmid: 10720515
references.citation: Ann Rheum Dis. 2005 Mar;64(3):487-90
references.pmid: 15331395
references.citation: Arthritis Rheum. 2003 Dec;48(12):3615-6
references.pmid: 14674019
references.citation: J Rheumatol. 1998 Oct;25(10):1991-4
references.pmid: 9779856
references.citation: Int Immunol. 1999 Apr;11(4):553-9
references.pmid: 10323208
references.citation: Clin Immunol. 2007 May;123(2):148-54
references.pmid: 17363330
references.citation: Arch Dis Child. 1997 Dec;77(6):530-4
references.pmid: 9496193
references.citation: Scand J Rheumatol. 2008 Jan-Feb;37(1):13-7
references.pmid: 18189189
references.citation: Clin Exp Rheumatol. 2003 May-Jun;21(3):351-4
references.pmid: 12846056