Journal
ARTHRITIS & RHEUMATOLOGY
Volume 67, Issue 1, Pages 140-151Publisher
WILEY-BLACKWELL
DOI: 10.1002/art.38873
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Funding
- NIH/National Center for Advancing Translational Science (NCATS) UCLA CTSI grant [UL1TR000124]
- NIH from the National Institute of Arthritis and Musculoskeletal and Skin Diseases [P01-AR-052915]
- National Health and Medical Research Council of Australia
- University of Queensland Diamantina Institute
- Saal van Zwanenbergstichting, The Netherlands
- National Eye Institute [R01-EY013139]
- Australian National Health and Medical Research Council
- Arthritis Society, Canada
- NIH (National Institute of Arthritis and Musculoskeletal and Skin Diseases) [P01-052915, R01-AR-046208]
- Research to Prevent Blindness, New York, New York
- Arthritis Research UK [19536, 18797]
- National Ankylosing Spondylitis Society
- NIHR Thames Valley Comprehensive Local Research Network
- AbbVie
- Amgen
- Janssen Pharmaceuticals
- UCB
- Celgene
- Pfizer
- Novartis
- Roche
- Versus Arthritis [20796, 19356] Funding Source: researchfish
- NATIONAL CENTER FOR ADVANCING TRANSLATIONAL SCIENCES [UL1TR000371, UL1TR000124] Funding Source: NIH RePORTER
- NATIONAL EYE INSTITUTE [R01EY013139] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF ARTHRITIS AND MUSCULOSKELETAL AND SKIN DISEASES [R01AR046208, P01AR052915] Funding Source: NIH RePORTER
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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 x 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 x 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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