IL-23 receptor (IL-23R) gene protects against pediatric Crohnʼs disease

Abstract

Background-The IL-23 receptor (IL-23R) has been found to be associated with small bowel Crohn's disease (CD) in a whole genome association study. Specifically, the rare allele of the R381Q single nucleotide polymorphism (SNP) conferred protection against CD. It is unknown whether IL-23R is associated with IBD in children. The aim was to examine the association of IL-23R with susceptibility to IBD in pediatric patients.

Relation of an interleukin-23 receptor gene polymorphism to graft-versus-host disease after hematopoietic-cell transplantation

“…3 Here, we report that an uncommon coding variant of the IL-23R (1142G4A) confers strong protection against the occurrence of severe acute GVHD after transplant as it has been already shown for inflammatory bowel disease recently by Duerr and coworkers and others. 10,11 The protective effect of the IL-23R gene variant on acute GVHD occurred primarily when the gene variant …”

“…[3][4][5][6][7][8][9] Recently, a gene variant of the interleukin-23 receptor (IL-23R-1142G4A) was found to be strongly associated with Crohn's disease. 10,11 IL-23 is a new member of the IL-12 family that plays a critical role in promoting inflammatory responses mediated by type 1 helper T cells. IL-23 and IL-12 share same molecule structure.…”

Detailed genetic characterization of the interleukin-23 receptor in psoriasis

“…Detailed genetic characterization VE Garcia et al diseases including IBD (particularly adult and pediatric Crohn's disease), [16][17][18][19][20][21][22][23][24] AS, 25,26 and GO. 27 It is possible that IL23R variants also underlie susceptibility to celiac disease, 28 Graves' disease without ophthalmopathy 27 and multiple sclerosis, 28,29 although the evidence is not currently strong for celiac disease and Graves' disease without opthalmopathy and is contradictory for multiple sclerosis.…”

“…11 These results have been verified in four independent studies [12][13][14][15] and have paralleled association studies in related diseases. One of the IL23R missense SNPs implicated in psoriasis, R381Q, has also been strongly associated with several autoinflammatory phenotypes: several studies have found R381Q-mediated predisposition to adult inflammatory bowel disease (IBD), especially Crohn's disease [16][17][18][19][20][21] and pediatric Crohn's disease in individuals of European descent, [22][23][24] two sizable studies reported association of multiple IL23R SNPs with ankylosing spondylitis (AS) 25,26 and a North American study demonstrated IL23R susceptibility for Graves' ophthalmopathy (GO). 27 IL23R polymorphisms have also been studied in celiac disease with mildly significant results 28 and multiple sclerosis with conflicting results.…”

Protective role of R381Q (rs11209026) polymorphism in IL-23R gene in immune-mediated diseases: A comprehensive review

“…Another study of CD in an Ashkenazi Jewish (AJ) population indicated a rare IL-23R R381Q variant was more frequent among AJ controls than among AJ CD patients (7% vs 2%, respectively), indicating a significant reduction in CD risk for carriers (Venegas et al 2008;Yu et al 2012). The association of this particular variant SNP with a decreased risk of CD has also been confirmed in pediatric populations (Dubinsky et al 2007) and in a large UK database studied by the Wellcome Trust (see Burton et al 2007). There are different frequencies of R381Q variants in populations of patients with various immune-mediated diseases and, thus, in control groups in different studies.…”