Negative association between the chemokine receptor CCR5-Δ32 polymorphism and rheumatoid arthritis: a meta-analysis

Abstract

Rheumatoid arthritis (RA) is characterized by synovial inflammation mediated by T-cells, monocytes and macrophages. The homing of these cells to the inflamed synovium is regulated by chemokine-receptors and their ligands. A 32-basepair deletion (D32) in the gene encoding CCR5, a chemokine-receptor, results in a non-functional receptor. A negative association between CCR5-D32 and RA has been described, although other studies found no associations. Furthermore, the observation that individuals homozygous for CCR5-D32 develop RA has raised questions about the role of CCR5-D32. This meta-analysis of all published case-control association studies confirms the negative association between CCR5-D32 and RA (Odds Ratio ¼ 0.65; 95% confidence intervals ¼ 0.55-0.77; Po0.0001), suggesting that CCR5-D32 is protective against the development of RA. CCR5 blockade in animal models of RA results in amelioration of arthritis, suggesting that CCR5 blockade could also modify disease in patients with RA.

CC Chemokine Receptors and Chronic Inflammation—Therapeutic Opportunities and Pharmacological Challenges

“…A meta-analysis of five case-control studies with European participants demonstrated a mean allele frequency of 6% for D32 in RA patients and 10% in controls (Prahalad, 2006). A significant negative association of the D32 allele with CC Chemokine Receptors in Inflammation RA was identified, indicating that this polymorphism is protective.…”

The CCR5-∆32 Mutation: Impact on Disease Outcome in Individuals with Hepatitis B Infection in the Southern Khorasan Population (East of Iran)

“…As was proved, this mutation has a protective role against chronic HBV infection and HIV, and also leads to a non-functional receptor that could modify disease in Rheumatoid arthritis patients, so it is concluded that the population of Birjand has greater hereditary susceptibility to chronic HBV infections, HIV, and Rheumatoid arthritis, compared to Europeans in terms of the CCR5 ∆32 mutation (13,14,18).…”

“…chromosome 3. One of the mutant types of the gene produces a non-functional receptor that is called CCR5∆32, which results from deletion of a specific sequence of 32 base-pairs (12,13).…”

Four novel coeliac disease regions replicated in an association study of a Swedish–Norwegian family cohort

“…The CCR5-D32 results in a complete lack of surface expression of CCR5, and individuals who are homozygous for CCR5-D32/32 have been shown to be protected against HIV because CCR5 is a co-receptor for this virus. 23 A protective effect of CCR5-D32 has also been reported for inflammatory diseases such as rheumatoid arthritis 24 although conflicting results exist. 25 A correlation between the CCR5-D32 and copy number variation within the CCL3L1 gene has been found to enhance HIV/AIDS susceptibility, 26 as well as increase the risk of developing systemic lupus erythematosus.…”