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Abstract
BackgroundAssociation of the interleukin-23 receptor (IL23R) with inflammatory bowel disease (IBD) has been confirmed in several populations. IL23R also associates with psoriasis, suggesting that the gene may be an important candidate for many chronic inflammatory diseases.MethodsWe studied association of single-nucleotide variants in IL23R with IBD in Swedish patients, in both Crohn's disease (CD) and ulcerative colitis (UC) subsets. The same genetic variants were also studied in Finnish patients with psoriasis or celiac disease, and in Hungarian and Italian patients with celiac disease.ResultsAssociation of IL23R with IBD was replicated in our Swedish patients, and linkage and association of the IL23R region with psoriasis was found in the Finnish population. The IL23R region was also linked to celiac disease in Finnish families, but no association of IL23R variants with celiac disease was found in the Finnish, Hungarian or Italian samples.ConclusionOur study is the first to demonstrate association of IL23R with CD and UC in Swedish patients with IBD. It is also the first study to report linkage and association of the IL23R region with psoriasis in the Finnish population. Importantly, this is the first report of linkage of the IL23R region to celiac disease, a chronic inflammatory condition in which IL23R has not been previously implicated.
Highlights
Association of the interleukin-23 receptor (IL23R) with inflammatory bowel disease (IBD) has been confirmed in several populations
Given the chronic inflammatory nature of both conditions, as well as the tissue targeted by the immune response, we hypothesised that these same single-nucleotide polymorphisms (SNPs) in the IL23R region might play a role in celiac disease- a chronic inflammatory enteropathy caused by exposure to dietary gluten that can manifest as a blistering cutaneous disease [24]
The strongest associations were observed for SNPs rs11465804*G with the combined IBD dataset (CD and ulcerative colitis (UC) cases; p = 0.002, Odds ratios (OR) 0.42) and rs10489629*C with the UC cohort only (p = 0.002, OR 0.72)
Summary
Association of the interleukin-23 receptor (IL23R) with inflammatory bowel disease (IBD) has been confirmed in several populations. Association of genetic markers in the interleukin-23 receptor (IL23R) gene, and the intergenic region between IL23R and IL12RB2, with inflammatory bowel disease (IBD) was first identified in 2006 [1]. This association has since been replicated in both Crohn's disease (CD) and ulcerative colitis (UC) [2,3,4,5,6,7,8,9,10], which are the two most frequent types of IBD, and in paediatric CD [11,12,13], psoriasis [1417] and ankylosing spondylitis [18]. Association of IL23R with celiac disease was studied in three populations (Finnish, Italian and Hungarian) due to heterogeneous allele and/or haplotype frequencies in different population groups, where a functional variant may explain a significant part of disease risk in one population but not another
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