Genetic Dissection of Acute Anterior Uveitis Reveals Similarities and Differences in Associations Observed With Ankylosing Spondylitis
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Date
2015
Authors
Robinson, Philip Cameron
Claushuis, Theodora A M
Cortes, Adrian
Martin, Tammy M
Evans, David M
Leo, Paul
Mukhopadhyay, Pamela
Bradbury, Linda A
Cremin, Katie
Harris, Jessica Aaron
Journal Title
Journal ISSN
Volume Title
Publisher
John Wiley & Sons
Rights
Copyright © 2015, American College of Rheumatology
Rights Holder
American College of Rheumatology
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.
Description
Author manuscript available from PMC http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4302162/
Keywords
High-density genotyping, Genetics, Acute anterior uveitis
Citation
Robinson, P. C., Claushuis, T. A. M., Cortes, A., Martin, T. M., Evans, D. M., Leo, P., Mukhopadhyay, P., Bradbury, L. A., Cremin, K., Harris, J., Maksymowych, W. P., Inman, R. D., Rahman, P., Haroon, N., Gensler, L., Powell, J. E., van der Horst-Bruinsma, I. E., Hewitt, A. W., Craig, J. E., Lim, L. L., Wakefield, D., McCluskey, P., Voigt, V., Fleming, P., Spondyloarthritis Research Consortium of Canada, Australio-Anglo-American Spondylitis Consortium, International Genetics of Ankylosing Spondylitis Consortium, Wellcome Trust Case Control Study 2, Degli-Esposti, M., Pointon, J. J., Weisman, M. H., Wordsworth, B. P., Reveille, J. D., Rosenbaum, J. T. and Brown, M. A. (2015), Genetic Dissection of Acute Anterior Uveitis Reveals Similarities and Differences in Associations Observed With Ankylosing Spondylitis. Arthritis & Rheumatology, 67: 140–151. doi: 10.1002/art.38873