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. 2010 Mar;69(3):567-70.
doi: 10.1136/ard.2008.106161. Epub 2009 Apr 14.

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

Hans Ulrich Scherer  1 , Michael P M van der Linden, Fina A S Kurreeman, Gerrie Stoeken-Rijsbergen, Saskia le Cessie, Tom W J Huizinga, Annette H van der Helm-van Mil, René E M Toes
Affiliations

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

Hans Ulrich Scherer et al. Ann Rheum Dis. 2010 Mar.

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 alpha-induced protein 3 (TNFAIP3). TNFAIP3 is a negative regulator of NF-kappaB 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.

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Conflict of interest statement

Competing interests: None.

Figures

Figure 1
Figure 1
Development of median Sharp van der Heijde scores plotted according to genotype/allele in ACPA+ (left column) and ACPA− (right column) patients with RA. Year 0 equals baseline-values. Regression analysis was performed in order to estimate the average increase (slope) in Sharp van der Heijde scores over time. Slopes were subsequently compared using the non-parametric Mann–Whitney test (for the ACPA+ subgroup: p=0.37 (rs1878658); p=0.007 (rs675520); p=0.021 (rs9376293); p=0.05 (rs10499194); p=0.76 (rs6920220)).
See this image and copyright information in PMC

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