Genetic Dissection of Acute Anterior Uveitis Reveals Similarities and Differences in Associations Observed With Ankylosing Spondylitis. Issue 1 (January 2015)

• Record Type: Journal Article
• Authors: Robinson, Philip C.; Claushuis, Theodora A. M.; Cortes, Adrian; Martin, Tammy M.; Evans, David M.; Leo, Paul; Mukhopadhyay, Pamela; Bradbury, Linda A.; Cremin, Katie; Harris, Jessica; Maksymowych, Walter P.; Inman, Robert D.; Rahman, Proton; Haroon, Nigil; Gensler, Lianne; Powell, Joseph E.; van der Horst‐Bruinsma, Irene E.; Hewitt, Alex W.; Craig, Jamie E.; Lim, Lyndell L.; Wakefield, Denis; McCluskey, Peter; Voigt, Valentina; Fleming, Peter; Spondyloarthritis Research Consortium of Canada, Australio-Anglo-American Spondylitis Consortium, International Genetics of Ankylosing Spondylitis Consortium, Wellcome Trust Case Control Study 2; Degli‐Esposti, Mariapia; Pointon, Jennifer J.; Weisman, Michael H.; Wordsworth, B. Paul; Reveille, John D.; Rosenbaum, James T.; Brown, Matthew A.;
• Is Part Of: Arthritis & rheumatology. Volume 67:Issue 1(2015)
• Page Start: 140
• Page End: 151
• Publication Date: 2015-01
• Subjects: Arthritis -- Periodicals; Rheumatism -- Periodicals; 616.72
• DOI: 10.1002/art.38873
• Languages: English
• ISSNs: 2326-5191

Abstract

<abstract abstract-type="main"> <title> <x xml:space="preserve">Abstract</x> </title> <sec id="art38873-sec-0001" sec-type="section"> <title>Objective</title> <p>To use high‐density genotyping to investigate the genetic associations of acute anterior uveitis (AAU) in patients with and those without ankylosing spondylitis (AS).</p> </sec> <sec id="art38873-sec-0002" sec-type="section"> <title>Methods</title> <p>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 <italic>ANTXR2</italic> for its putative effect in AAU. <italic>ANTXR2</italic> expression in mouse eyes was investigated by real‐time quantitative reverse transcription–polymerase chain reaction.</p> </sec> <sec id="art38873-sec-0003" sec-type="section"> <title>Results</title> <p>A comparison between all patients with AAU and healthy control subjects showed strong association over <italic>HLA–B</italic>, corresponding to the <italic>HLA–B27</italic> tag single‐nucleotide polymorphism rs116488202. The association of 3 non–major histocompatibility complex loci, <italic>IL23R</italic>, the intergenic region 2p15, and <italic>ERAP1</italic>, reached genome‐wide significance (<italic>P</italic> < 5 × 10<sup>−8</sup>). Five loci harboring the immune‐related genes <italic>IL10–IL19</italic>, <italic>IL18R1–IL1R1</italic>, <italic>IL6R</italic>, the chromosome 1q32 locus harboring <italic>KIF21B</italic>, as well as the eye‐related gene <italic>EYS</italic>, were also associated, reaching a suggestive level of significance (<italic>P</italic> < 5 × 10<sup>−6</sup>). Several previously confirmed AS associations demonstrated significant differences in effect size between AS patients with AAU and AS patients without AAU. <italic>ANTXR2</italic> expression varied across eye compartments.</p> </sec> <sec id="art38873-sec-0004" sec-type="section"> <title>Conclusion</title> <p>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 <italic>IL10</italic> and <italic>IL18R1</italic> are shared with inflammatory bowel disease, suggesting common etiologic pathways.</p> </sec> </abstract>