RESEARCH - Association of the 6q23 region with the rate of joint destruction in RA

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Ann Rheum Dis. 2009 Apr 16.

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

rheumatoid arthritis.

Scherer HU, van der Linden MP, Kurreeman FA, Stoeken-Rijsbergen G, le

Cessie S, Huizinga TW, van der Helm-van Mil AH, Toes RE.

Department of Rheumatology, Leiden University Medical Centre, Leiden,

Netherlands.

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 alpha-induced protein 3

(TNFAIP3). TNFAIP3 is a negative regulator of NFkappaB 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.

PMID: 19366996

http://www.ncbi.nlm.nih.gov/pubmed/19366996

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