Arthritis & Rheumatism, Volume 60,
October 2009 Abstract Supplement

The 2009 ACR/ARHP Annual Scientific Meeting
Philadelphia October 16-21, 2009.

Genomewide Scan in Acute Anterior Uveitis: Similarities and Differences with Genes Associated with Ankylosing Spondylitis

Martin1,  Tammy M., Evans2,  David M., Danoy3,  Patrick, Smith1,  Justine R., Ward4,  Michael M., Weisman5,  Michael H., The Australo-Anglo-American Spondylitis Consortium,  

Oregon Health & Science Univ, Portland, OR,
University of Bristol, Bristol, United Kingdom,
Diamantina Institute, University of Queensland, Brisbane, Queensland, Australia,
NIH/NIAMS, Bethesda, MD,
Cedars-Sinai Med Ctr, LA, CA,
University of Texas Medical School at Houston, Houston, TX


Acute anterior uveitis (AAU) or iritis, complicates ~40% of cases of ankylosing spondylitis (AS), and can occur in the absence of AS. Both AS and AAU are associated with HLA-B27, and there is evidence to suggest that other genes are involved in each disease. This study aimed to identify genes involved in AAU and to compare those genes with the known genes involved in AS.


952 cases with uveitis (with or without AS) and 1380 AS cases without uveitis were available for study. These were identified from cases enrolled in the TASC AS genomewide association study (n=2082), or were recruited separately having presented with AAU (n=250). TASC cases were genotyped with lllumina 370CNV chips and non-TASC samples with Illumina 610 chips. Healthy controls used were from the Illumina iControl database, and had been cleaned for white European ancestry using ancestry informative markers. Datasets were compared using the Cochrane-Armitage test for trend as implemented in PLINK. Study activities were conducted under approved human subjects protocols.


Comparing uveitis cases with AS cases without uveitis, association was observed at chromosome 1p35.1 with SNPs in the gene CSMD2 (CUB and Sushi multiple domains 2; rs732889, P= 1.8×10-7). Association was also observed with SNPs in the chromosomal regions 4q32.3 (rs11100530, P=2.0×10-6) and 15q22.1 (rs1122208, P=5.7×10-7). No genes are encoded in these regions. No association was seen between CSMD2, or the chromosome 4 or 15 regions, with AS in comparisons of AS cases vs healthy controls, suggesting that the associations observed are with AAU rather than primarily with AS. The CSMD2 protein is expressed primarily in brain and related tissues, including the ciliary ganglia. It has unknown function and belongs to a family of transmembrane proteins with large extracellular domains containing alternating CUB and Sushi motifs. Based on the absence of differences between uveitis compared to AS without uveitis at known AS loci, these data also support uveitis associations with MHC, IL23R, ERAP1, chromosome 2p15, 21q22, IL1R2 and ANTXR2.


This study suggests that there is great similarity between the genes involved in AS and in AAU, and that the major genes involved in AS that are known thus far are similarly associated with AAU. In addition, three loci were identified, including the gene CSMD2, which have a greater association in AAU cases than in AS alone, suggesting that these genes are independent risk factors for AAU. Funding: NIH, RPB, NHMRC.

To cite this abstract, please use the following information:
Martin, Tammy M., Evans, David M., Danoy, Patrick, Smith, Justine R., Ward, Michael M., Weisman, Michael H., et al; Genomewide Scan in Acute Anterior Uveitis: Similarities and Differences with Genes Associated with Ankylosing Spondylitis [abstract]. Arthritis Rheum 2009;60 Suppl 10 :1231
DOI: 10.1002/art.26305

Abstract Supplement

Meeting Menu