Association of the 6q23 region with the rate of joint destruction in rheumatoid arthritis.
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.
Scherer
Hans Ulrich
HU
Department of Rheumatology, Leiden University Medical Centre, RC, Leiden, The Netherlands. r.e.m.toes@lumc.nl
van der Linden
Michael P M
MP
Kurreeman
Fina A S
FA
Stoeken-Rijsbergen
Gerrie
G
Cessie
Saskia le
Sl
Huizinga
Tom W J
TW
van der Helm-van Mil
Annette H
AH
Toes
René E M
RE
D000483:Alleles; D001172:Arthritis, Rheumatoid / Q000000981:diagnostic imaging / Q000235:genetics* / Q000276:immunology; D002896:Chromosomes, Human, Pair 6 / Q000235:genetics* / Q000276:immunology; D004812:Epidemiologic Methods; D005819:Genetic Markers; D005838:Genotype; D006801:Humans; D010456:Peptides, Cyclic / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D011859:Radiography
D005819:Genetic Markers; D010456:Peptides, Cyclic; C487763:cyclic citrullinated peptide