TY - JOUR
T1 - Genetic dissection of acute anterior uveitis reveals similarities and differences in associations observed with ankylosing spondylitis
AU - Robinson, Philip C.
AU - Claushuis, Theodora A.M.
AU - Cortes, Adrian
AU - Martin, Tammy M.
AU - Evans, David M.
AU - Leo, Paul
AU - Mukhopadhyay, Pamela
AU - Bradbury, Linda A.
AU - Cremin, Katie
AU - Harris, Jessica
AU - Maksymowych, Walter P.
AU - Inman, Robert D.
AU - Rahman, Proton
AU - Haroon, Nigil
AU - Gensler, Lianne
AU - Powell, Joseph E.
AU - Van Der Horst-Bruinsma, Irene E.
AU - Hewitt, Alex W.
AU - Craig, Jamie E.
AU - Lim, Lyndell L.
AU - Wakefield, Denis
AU - McCluskey, Peter
AU - Voigt, Valentina
AU - Fleming, Peter
AU - Degli-Esposti, Mariapia
AU - Pointon, Jennifer J.
AU - Weisman, Michael H.
AU - Wordsworth, B. Paul
AU - Reveille, John D.
AU - Rosenbaum, James T.
AU - Brown, Matthew A.
N1 - Publisher Copyright:
© 2015 The Authors. Arthritis & Rheumatology is published by Wiley Periodicals, Inc.
PY - 2015/1/1
Y1 - 2015/1/1
N2 - 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.ObjectiveMethods 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.
AB - 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.ObjectiveMethods 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.
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U2 - 10.1002/art.38873
DO - 10.1002/art.38873
M3 - Article
C2 - 25200001
AN - SCOPUS:84919879973
SN - 2326-5191
VL - 67
SP - 140
EP - 151
JO - Arthritis and Rheumatology
JF - Arthritis and Rheumatology
IS - 1
ER -