ACR Meeting Abstracts

ACR Meeting Abstracts

Abstract Number: 595

A Genomewide Association Study of Anterior Uveiti

Dorith Claushuis1, Adrian Cortes2, Linda A. Bradbury1, Tammy M. Martin3, James T. Rosenbaum4, John D. Reveille5, Paul Wordsworth6, Jennifer Pointon6, Australo-Anglo-American Spondyloarthritis Consortium7, David Evans8, Paul Leo2, Pamela Mukhopadhyay2 and Matthew A. Brown2, 1Human Genetics Group, The University of Queensland Diamantina Institute, Brisbane, Australia, 2Human Genetics Group, The University of Queensland Diamantina Insititute, Brisbane, Australia, 3Ophthalmology/L467AD, Oregon Health & Science Univ, Portland, OR, 4Arthritis and Rheumatic diseases, Oregon Health and Science University, Portland, OR, 5Internal Medicine/Rheumatology, Univ of Texas Health Science Center at Houston, Houston, TX, 6Ndorms, Nuffield Orthopaedic Centre, Oxford, United Kingdom, 7Houston, TX, 8School of Social and Community Medicine, Bristol University, Bristol, United Kingdom

Meeting: 2012 ACR/ARHP Annual Meeting

Keywords:

Session Information

Title: Spondylarthritis and Psoriatic Arthritis - Pathogenesis, Etiology

Session Type: Abstract Submissions (ACR)

Background/Purpose: Anterior uveitis (AU) is the most common extra-articular manifestation of ankylosing spondylitis (AS), occurring in up to 30-40% of AS cases.  The aim of the current study was to investigate clinical associations of AS, and to identify genes associated with the risk of developing AU.     

Methods: 972 AS cases with AU (AS+AU+) and 1404 AS cases without AU (AS+AU-) were available for study.  All cases were of white European descent. A genomewide association study was performed using SNP data from the TASC and TASC-WTCCC2 AS studies, 291,537 SNPs being available in the merged dataset.  Case-control analysis comparing the AS+AU+ and AS+AU- cohorts was performed using Eigenstrat to control for population stratification effects.

Results:  Male and female AS cases were equally likely to develop AU.  As expected, AU complicating AS was strongly associated with AS disease duration (beta=0.027, P<10-6).  No association was seen with age, independent of AS disease duration.  Considering AS+AU+ cases in comparison with AS+AU- cases, no SNP achieved genomewide significance.  Three loci showed suggestive association with AU.  At chromosome 6q26, two SNPs in the PARK2 gene achieved P<10-5 (rs2849576, p=7.6×10-6; rs13205287, p=2.0×10-6).   Five SNPs (rs379796, rs419519, rs445890, rs452186, rs45218) in an intergenic region on chromosome 4q33 achieved P=9.0×10-6-9.5×10-6.  Association was noted with HLA-B27 (antigen carriage, odds ratio 2.58, P=5.6×10-8).  There was a marginal association of B27-homozygosity in this analysis (odds ratio 2.1, P=0.06).  No known AS locus was differentially associated in AS+AU+ cases in comparison with AS+AU- cases.

Conclusion: This analysis found that with the exception of HLA-B27, no differences were identified between AS+AU+ and AS+AU- cases.  The study was adequately powered to identify moderately large genetic effects, but not small-moderate genetic effects for which larger studies will be required.  Further, as all patients studied have AS, whether genetic associations of AS-AU+ cases are different to those of AS+AU+ remains unclear.  Nonetheless, these findings suggest that AU has very similar genetic risk factors to AS, and therefore that they likely share similar aetiopathogenisis.

Disclosure:

D. Claushuis,
None;

A. Cortes,
None;

L. A. Bradbury,
None;

T. M. Martin,
None;

J. T. Rosenbaum,
None;

J. D. Reveille,
None;

P. Wordsworth,
None;

J. Pointon,
None;

D. Evans,
None;

P. Leo,
None;

P. Mukhopadhyay,
None;

M. A. Brown,
None.

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