Analysis of Interleukin-23 Receptor (IL23R) Gene Polymorphisms in Idiopathic Uveitis

Abstract

Purpose: : Interleukin-23 (IL-23) is a pivotal cytokine in the polarization of T cells. Single nucleotide polymorphisms (SNPs) in the gene encoding the IL-23 receptor (IL23R) are associated with susceptibility to inflammatory bowel disease, psoriasis, and ankylosing spondylitis. Several of these SNPs have also been implicated in acute anterior uveitis, even when limiting the analysis to subjects without ankylosing spondylitis. In this report, we test the hypothesis that IL23R contributes to the genetic risk of uveitis in a cohort with idiopathic uveitis.

Methods: : Enrollment of subjects, sample procurement and genetic analysis were in compliance with the Declaration of Helsinki and under an IRB-approved protocol. Idiopathic uveitis was assessed by chart review (EJ) and defined as uveal inflammation without evidence of associated systemic disease, underlying infection, or ocular syndrome by appropriate diagnostics. Genotyping of 11 SNPs located in or near IL23R was performed on PCR-amplified genomic DNA using denaturing HPLC and/or direct DNA sequencing in both directions. Allele frequencies were compared using the Fisher’s exact test.

Results: : The idiopathic uveitis cohort consisted of 81 subjects (58 female; 23 male) and was 88% Caucasian. The healthy control cohort was comprised of 106 individuals (63 female; 43 male) with no history of inflammatory disease and was 92% Caucasian. The SNP allele frequencies in the controls were similar to other published cohorts. None of the 11 SNPs tested were found to be statistically different between the cases and controls, P > 0.05.

Conclusions: : Even though IL23R contributes to acute anterior HLA-B27 associated uveitis in the absence of systemic disease, we have found no evidence that IL23R is involved in susceptibility to idiopathic uveitis. A much larger cohort of cases would be needed to determine if IL23R contributes to phenotypic subsets of idiopathic uveitis.

Keywords: genetics • uveitis-clinical/animal model • cytokines/chemokines