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Tammy Martin, Patrick Stauffer, Erin Patridge, Christopher Younkins, Mia Burcham, Justine Smith; Genetic analysis of risk alleles associated with inflammatory bowel disease in acute anterior uveitis. Invest. Ophthalmol. Vis. Sci. 2013;54(15):5202.
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To determine if inflammatory bowel disease (IBD) risk alleles are associated with susceptibility to acute anterior uveitis (AAU). Extra-articular manifestations of spondyloarthritis (SpA) include AAU and IBD. Numerous genetic associations for IBD have been found, many involving T cell biology and implicating pathogenic Th17 cells. JAK2 and TYK2 play a critical role in IL-23R signaling and are associated with ulcerative colitis and Crohn disease. IL-7R signaling is important in several pathways that impact the homeostasis of Th17/Th1/Treg cell populations and is associated with ulcerative colitis.
The study was conducted under IRB approval. Validation of AAU and SpA was based on medical chart review. 167 subjects with AAU (94 female/73 male; 159 White) were included. Of these 86 were without history of SpA, while 57 had an ankylosing spondylitis diagnosis, 22 had histories consistent with axial disease, and 2 were with unknown axial disease status. 113 healthy controls were included. Genomic DNA from whole blood cells was genotyped by TaqMan SNP assays on the ViiA7 platform. Three SNPs were analyzed: rs10758669 (JAK2, 5’UTR), rs3194051 (IL7R, p.I356V), and rs12720356 (TYK2, p.I684S). Allele frequency differences between cases and controls were calculated by the Chi2 test. P values were uncorrected.
In comparing all AAU cases to controls, no significant difference was seen for the JAK2 or TYK2 SNPs, but the IL7R SNP was significant (P=0.0287, OR=0.646, 95% CI=0.436-0.957). This IL7R association was lost when comparing “AAU with SpA” to “controls” and strengthened in the comparison of “AAU without SpA” to “controls” (P=0.0112, OR=0.536, CI=0.330-0.871). Stratifying by the AAU subsets did not reveal any further significant results for the JAK2 SNP. However, while the “AAU with SpA” vs. “control” test remained not significant, the “AAU without SpA” vs. “control” test demonstrated an association with the TYK2 SNP (P=0.0127, OR=2.5712, CI=1.197-5.524).
This study provides evidence that IL7R and TYK2 may contribute to uveitis susceptibility. This notion is strengthened by the finding that the differences are more significant in the subset of AAU subjects without SpA. These two genes are known to be associated with susceptibility to IBD, but not to ankylosing spondylitis, consistent with the lack of significant findings in the AAU subset with SpA.
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