Association of the CCR5 gene with juvenile idiopathic arthritis.
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.
Hinks
A
A
Manchester Academy of Health Sciences, The University of Manchester, UK. Anne.Hinks@manchester.ac.uk
Martin
P
P
Flynn
E
E
Eyre
S
S
Packham
J
J
Barton
A
A
Worthington
J
J
Thomson
W
W
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
D019713:Receptors, CCR5
Genes Immun. 2006 Sep;7(6):468-75
16775617
Rheumatology (Oxford). 2006 Apr;45(4):365-8
16418195
Nat Genet. 2007 Dec;39(12):1431-3
17982455
Arthritis Rheum. 2000 Apr;43(4):765-74
10765921
Genes Immun. 2000;1(4):288-9
11196706
J Biol Chem. 2002 Jan 18;277(3):2287-301
11604406
Arthritis Rheum. 1999 May;42(5):989-92
10323455
Arthritis Rheum. 2009 Jan;60(1):251-7
19116909
J Rheumatol. 1998 Aug;25(8):1462-5
9712084
Am J Hum Genet. 2007 Sep;81(3):559-75
17701901
Rheumatology (Oxford). 2002 Dec;41(12):1428-35
12468825
J Rheumatol. 2004 Feb;31(2):390-2
14760812
AIDS. 1999 Mar 11;13(4):455-63
10197373
Arthritis Rheum. 1998 Jun;41(6):1135-6
9627027
Ann Rheum Dis. 2010 Jun;69(6):1049-53
19674979
Genes Immun. 2010 Mar;11(2):194-8
20072139
Science. 1995 Dec 15;270(5243):1811-5
8525373
Nature. 1998 Jan 22;391(6665):344-5
9450746
J Immunol. 2009 Jan 1;182(1):171-82
19109148
Proc Natl Acad Sci U S A. 2003 Sep 2;100(18):10411-6
12915736
N Engl J Med. 2008 Dec 25;359(26):2767-77
19073967
Genes Immun. 2006 Apr;7(3):264-8
16541097
BMC Med Genet. 2007 Jun 12;8:33
17565662
Arthritis Res Ther. 2009;11(3):R91
19538721
Rheumatology (Oxford). 2008 Jul;47(7):991-5
18417527
J Clin Immunol. 2001 Mar;21(2):116-25
11332650
Arthritis Rheum. 2009 Mar;60(3):901-4
19248117
J Infect Dis. 2000 Mar;181(3):933-8
10720515
Ann Rheum Dis. 2005 Mar;64(3):487-90
15331395
Arthritis Rheum. 2003 Dec;48(12):3615-6
14674019
J Rheumatol. 1998 Oct;25(10):1991-4
9779856
Int Immunol. 1999 Apr;11(4):553-9
10323208
Clin Immunol. 2007 May;123(2):148-54
17363330
Arch Dis Child. 1997 Dec;77(6):530-4
9496193
Scand J Rheumatol. 2008 Jan-Feb;37(1):13-7
18189189
Clin Exp Rheumatol. 2003 May-Jun;21(3):351-4
12846056