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T. M. Martin, J. R. Smith, T. M. Doyle, K. Goodwin, E. B. Suhler, N. K. Wade, F. Mackensen, M. A. Brown, J. D. Reveille, J. T. Rosenbaum; The Interleukin-23 Receptor Is a New Susceptibility Gene for Acute Anterior Uveitis. Invest. Ophthalmol. Vis. Sci. 2008;49(13):3236. doi: https://doi.org/.
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The gene encoding the interleukin-23 receptor (IL23R) has recently been implicated in susceptibility to inflammatory bowel disease, psoriasis, and ankylosing spondylitis. In this study, we tested the hypothesis that IL23R contributes to the genetic risk of acute anterior uveitis (AAU), the most common form of immune-mediated uveitis and the phenotype associated with spondyloarthritis.
Subjects with AAU, or healthy control subjects, were recruited under IRB approved protocols. The phenotype of AAU was verified by ophthalmology chart review (JRS). Genomic DNA was extracted from blood cells and amplified using specific PCR primers. Genotyping of 11 snps located in or near IL23R was performed by denaturing HPLC and/or direct DNA sequencing in both directions. Case-control comparisons were analyzed using the Fisher’s exact test.
The AAU cohort consisted of 151 subjects (86 female, 65 male) and was 96.7% Caucasian by self-report. Within this cohort, 85 subjects had no history of ankylosing spondylitis (AS), 59 subjects had a diagnosis of AS and the remaining 7 subjects were considered to be "probable" for AS lacking adequate medical records. The healthy control cohort was comprised of 104 individuals (60 female, 44 male) with no history of inflammatory disease and was 92.3% Caucasian. The allele frequencies of each snp in the control group were similar to other published cohorts. Of the eleven IL23R snps that were genotyped, seven were found to be associated with AAU when compared to the control group: rs1004819 (p=0.0325), rs7517847 (p=<0.0001), rs10489629 (p=0.0010), rs1343151 (p=<0.0001), rs10889677 (p=<0.0001), rs11209032 (p=0.0001), rs1495965 (p=0.0063). Stratification of the AAU cohort into those subjects with or without AS resulted in 6/7 snps remaining significant in the AAU only subgroup, while 4/7 snps remained significant, with weaker p values, in the AAU+AS subgroup.
This study is the first report to show an association of IL23R polymorphisms with AAU in the absence of AS. The functional significance of these findings with regard to disease mechanisms has yet to be elucidated. However, IL-23 is a pivotal cytokine in T lymphocyte polarization during inflammation.
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