RESEARCH - Negative association of CCR5 d32 polymorphism with RA

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Ann Rheum Dis. 2004 Aug 26 [Epub ahead of print]

Evidence for negative association of the chemokine receptor CCR5 d32

polymorphism with rheumatoid arthritis.

Pokorny V, McQueen F, Yeoman S, Merriman M, Merriman T, on A,

Highton J, McLean L.

University of Auckland, New Zealand.

OBJECTIVES: Chemokines of the CC (beta) family are important for the

attraction and activation of T lymphocytes and macrophages. Ligands of

the chemokine receptor CCR5 including MIP-1a, MIP-1b and RANTES have

been implicated in rheumatoid arthritis. Some studies have suggested a

decrease in the non-functional CCR5 variant with a 32bp deletion (d32)

in patients with RA. We tested the CCR5 d32 polymorphism for negative

association with RA in a New Zealand cohort. METHODS: Five hundred and

sixteen Caucasian RA patients and 985 healthy controls were investigated

by polymerase chain reaction (PCR) amplification of the region flanking

the known CCR5 d32 deletion, and the frequencies of CCR5d32 compared. In

addition an early RA (ERA) cohort of 92 patients was followed

prospectively for two years, with assessment of disease severity and

outcome. RESULTS: Twelve (1.2%) control subjects were homozygous for

d32, whereas no d32 homozygous RA patients were detected (p = 0.011).

Fifty-six (11%) patients were heterozygous for the d32 polymorphism

(d32/wt) compared to 169/985 (17%) of controls (p = 0.0017). The CCR5

d32 gene frequency was significantly lower in the RA patients than in

the healthy controls (frequency of 0.054 and 0.097, respectively; p <

0.0001). The frequency of CCR5 d32 did not differ significantly

according to in disease severity or outcome in the prospective ERA

cohort, nor with HLA-DRB1 status.

CONCLUSION: This study provides further evidence for a protective effect

of the CCR5 d32 variant on RA, consistent with a role for CCR5 and its

ligands in disease pathogenesis.

PMID: 15331395

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve & db=PubMed & list_uids=1\

5331395 & dopt=Abstract

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