Evidence for association of an interleukin-23 receptor variant independent of the R381Q variant with rheumatoid arthritis
Jade E Hollis-Moffatt 1, Marilyn E Merriman 1, Rachel A Rodger 1, Kerry A Rowley 1, Peter T Chapman 1, Nicola Dalbeth 2, Peter J Gow 3, Andrew A Harrison 1, John Highton 4, Peter BB Jones 2, John L O'Donnell 5, Lisa K Stamp 6 and Tony R Merriman 1*
1 University of Otago, New Zealand
2 University of Auckland, New Zealand
3 Middlemore Hospital, New Zealand
4 University of Otago School of Medicine, New Zealand
5 Christchurch Hospital, New Zealand
6 University of otago, New Zealand
* To whom correspondence should be addressed. E-mail: tony.merriman{at}stonebow.otago.ac.nz.
Accepted 10 July 2008
 | Abstract |
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Objective: The rare allele of a non-synonymous interleukin-23 receptor (IL23R) single nucleotide polymorphism (SNP) rs11209026 (p.Arg381Gln) confers strong protection against Crohn’s disease (CD) and psoriasis. Other IL23R variants also exhibit association with CD, genetically independent of rs11209026. In rheumatoid arthritis (RA), interleukin-23 is an important determinant of the production of interleukin-17A, a cytokine of consequence in both inflammation and bone destruction. Whilst there is no previous support for strong association of IL23R with RA, the possibility of a weaker role for IL23R variants in the etiology of RA cannot be eliminated.
Methods: We tested our New Zealand RA cohort for association with six IL23R single nucleotide polymorphisms and combined our data with a re-analysis of the Wellcome Trust Case Control Consortium data and a previously published Spanish data set. The combined data set totals over 3000 Caucasian cases and 3800 controls, which has sufficient power to detect a risk of as low as odds ratio (OR) = 1.2.
Results: Our data emphasize the lack of association of rs11209026 with RA (OR = 1.01 [0.88-1.16], P=0.86). However there was some evidence for association of rs1343151 with RA (OR=1.14 [1.06-1.22], P=4x10-4).
Conclusions: Whilst requiring further replication, these data further support a role for the IL-17A/IL-23 pathway in RA. Understanding how different variants of IL23R associate, at varying levels of strength, with contrasting groups of immune-mediated diseases (CD, psoriasis, ankylosing spondylitis, RA) will enhance knowledge on the etiology of these diseases.
