Objective: Two novel genetic polymorphisms on chromosome 6q23 are associated with sus-ceptibility to rheumatoid arthritis (RA). Both polymorphisms (rs6920220 and rs10499194) reside in a region close to the gene encoding tumor necrosis factor α-induced protein 3 (TNFAIP3). TNFAIP3 is a negative regulator of NFκB and as such involved in inhibiting TNF-Receptor mediated signalling effects. Interestingly, the initial associations were detected in patients with long-standing RA. However, no association was found for rs10499194 in a Swedish early arthritis cohort. As this could be caused by overrepresentation of patients with severe disease in cohorts with long-standing RA, we analyzed the effect of the 6q23 region on the rate of joint destruction.
Methods: Five single nucleotide polymorphisms (SNPs) in 6q23 were genotyped in 324 Dutch patients with early RA. Genotypes were correlated to progression of radiographic joint damage for a follow-up time of 5 years.
Results: Two polymorphisms (rs675520 and rs9376293) associated with severity of radio-graphic joint damage in ACPA+ patients. Importantly, the effects were present after correc-tion for confounding factors such as secular trends in treatment.
Conclusions: Our data associate the 6q23 region with the rate of joint destruction in ACPA+ RA.