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Abstract

Objective: To use high-density genotyping to investigate the genetic associations of acute anterior uveitis (AAU) in patients with and those without ankylosing spondylitis (AS).

Methods: We genotyped samples from 1,711 patients with AAU (either primary or combined with AS), 2,339 AS patients without AAU, and 10,000 control subjects on an Illumina Immunochip Infinium microarray. We also used data for AS patients from previous genome-wide association studies to investigate the AS risk locus ANTXR2 for its putative effect in AAU. ANTXR2 expression in mouse eyes was investigated by real-time quantitative reverse transcription-polymerase chain reaction.

Results: A comparison between all patients with AAU and healthy control subjects showed strong association over HLA-B, corresponding to the HLA-B27 tag single-nucleotide polymorphism rs116488202. The association of 3 non-major histocompatibility complex loci, IL23R, the intergenic region 2p15, and ERAP1, reached genome-wide significance (P < 5 × 10(-8)). Five loci harboring the immune-related genes IL10-IL19, IL18R1-IL1R1, IL6R, the chromosome 1q32 locus harboring KIF21B, as well as the eye-related gene EYS, were also associated, reaching a suggestive level of significance (P < 5 × 10(-6)). Several previously confirmed AS associations demonstrated significant differences in effect size between AS patients with AAU and AS patients without AAU. ANTXR2 expression varied across eye compartments.

Conclusion: These findings of both novel AAU-specific associations and associations shared with AS demonstrate overlapping but also distinct genetic susceptibility loci for AAU and AS. The associations in IL10 and IL18R1 are shared with inflammatory bowel disease, suggesting common etiologic pathways.

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Conflict of interest statement

No author has a potential conflict of interest in relation to this work.

Figures

Figure 1
Figure 1
Major histocompatibility complex association plot for all acute anterior uveitis versus healthy controls
Figure 2
Figure 2
Expression of ANTXR1 and ANTXR2 in eye compartments. Total RNA was isolated from different compartments of the eye, as well as the lung and real-time RT-PCR performed to determine the relative abundance of ANTRX1 and ANTRX2 mRNA by reference to L32 mRNA. The results represent mean and SEM from three independent experiments, each including triplicate samples
Figure 3
Figure 3
Proportion of ankylosing spondylitis patients with acute anterior uveitis by ankylosing spondylitis disease duration. Source: Ankylosing spondylitis GWAS patient cohort
See this image and copyright information in PMC

References

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