Association of the 6q23 region with the rate of joint destruction in rheumatoid arthritis

Abstract

Background: Two novel genetic polymorphisms on chromosome 6q23 are associated with susceptibility to rheumatoid arthritis (RA). Both polymorphisms (rs6920220 and rs10499194) reside in a region close to the gene encoding tumour necrosis factor α- induced protein 3 (TNFAIP3). TNFAIP3 is a negative regulator of NF- κB and is involved in inhibiting TNF- receptor- mediated signalling effects. Interestingly, the initial associations were detected in patients with longstanding RA. However, no association was found for rs10499194 in a Swedish cohort with early arthritis. This might be caused by over- representation of patients with severe disease in cohorts with longstanding RA. Objective: To analyse the effect of the 6q23 region on the rate of joint destruction. Methods: Five single nucleotide polymorphisms in 6q23 were genotyped in 324 Dutch patients with early RA. Genotypes were correlated with progression of radiographic joint damage for a follow- up time of 5 years. Results: Two polymorphisms (rs675520 and rs9376293) were associated with severity of radiographic joint damage in patients positive for anti- citrullinated protein/ peptide antibodies (ACPA). Importantly, the effects were present after correction for confounding factors such as secular trends in treatment. Conclusions: These data associate the 6q23 region with the rate of joint destruction in ACPA+ RA.