Acute anterior uveitis (AAU) describes an inflammation of the anterior uveal tract of the eye and is diagnosed by the presence of infiltrating leukocytes in the anterior chamber. For many patients, uveitis is a recurrent condition that may not respond well to the treatments available. A well-defined form of uveitis is anterior, acute (as opposed to chronic), sudden onset, recurrent and unilateral. This is the most common form of uveitis. In many, the disease is familial and is often associated with the marker, HLA-B27. We propose to identify uveitis susceptibility genes by conducting microsatellite genetic analyses in well-defined pedigrees. First, we propose to identify families with two or more members afflicted with AAU. This will be accomplished through a variety of sources including the North American Spondylitis Consortium, the uveitis clinic at Oregon Health Science University, various ophthalmologists around the U.S. who are members of the American Uveitis Society and/or Proctor Fellows, and the Spondylitis Association of America. We anticipate the enrollment of 200 multiplex AAU families. Second, the AAU phenotype of each study participant will be validated and blood will be drawn as a source of genomic DNA. Third, the Major Histocompatibility Complex haplotypes of each participant will be determined so as to analyze the contribution of these genes to the disease. Fourth, whole genome scan will be conducted and examined by sib pair analyses to identify regions of interest in the genome. Fifth, fine-scale mapping studies within the regions of interest will be done to identify candidate genes. These regions of interest will be those i) implicated in the susceptibility to related diseases, including ankylosing spondylitis, and ii) identified from our genome-wide scan. Sixth, we will determine the prevalence of candidate gene mutations among families with AAU. Seventh, we will enroll 100 patients with non-familial AAU in an association study and examine known gene polymorphisms implicated in AAU and other inflammatory diseases. This association study will also include patients with other forms of uveitis. Our goal of identifying genes (in addition to HLA-B27) that contribute to AAU susceptibility could have important therapeutic and preventative implications.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
5R01EY013139-03
Application #
6635713
Study Section
Visual Sciences A Study Section (VISA)
Program Officer
Chin, Hemin R
Project Start
2001-05-01
Project End
2005-04-30
Budget Start
2003-05-01
Budget End
2005-04-30
Support Year
3
Fiscal Year
2003
Total Cost
$387,572
Indirect Cost
Name
Oregon Health and Science University
Department
Ophthalmology
Type
Schools of Medicine
DUNS #
096997515
City
Portland
State
OR
Country
United States
Zip Code
97239
Robinson, Philip C; Claushuis, Theodora A M; Cortes, Adrian et al. (2015) Genetic dissection of acute anterior uveitis reveals similarities and differences in associations observed with ankylosing spondylitis. Arthritis Rheumatol 67:140-51
Abbasian, Javaneh; Martin, Tammy M; Patel, Sarju et al. (2012) Immunologic and genetic markers in patients with idiopathic ocular inflammation and a family history of inflammatory bowel disease. Am J Ophthalmol 154:72-7
Mackensen, F; David, F; Schwenger, V et al. (2011) HLA-DRB1*0102 is associated with TINU syndrome and bilateral, sudden-onset anterior uveitis but not with interstitial nephritis alone. Br J Ophthalmol 95:971-5
Martin, Tammy M; Rosenbaum, James T (2011) An update on the genetics of HLA B27-associated acute anterior uveitis. Ocul Immunol Inflamm 19:108-14
Kim, Hyun Soo; Choi, Dongseok; Lim, Lyndell L et al. (2011) Association of interleukin 23 receptor gene with sarcoidosis. Dis Markers 31:17-24
Levinson, Ralph D; Martin, Tammy M; Luo, Lihui et al. (2010) Killer cell immunoglobulin-like receptors in HLA-B27-associated acute anterior uveitis, with and without axial spondyloarthropathy. Invest Ophthalmol Vis Sci 51:1505-10
Agnani, S; Choi, D; Martin, T M et al. (2010) Gender and laterality affect recurrences of acute anterior uveitis. Br J Ophthalmol 94:1643-7
Saulsbury, Frank T; Wouters, Carine H; Martin, Tammy M et al. (2009) Incomplete penetrance of the NOD2 E383K substitution among members of a pediatric granulomatous arthritis pedigree. Arthritis Rheum 60:1804-6
Martin, Tammy M; Bye, Louise; Modi, Neil et al. (2009) Genotype analysis of polymorphisms in autoimmune susceptibility genes, CTLA-4 and PTPN22, in an acute anterior uveitis cohort. Mol Vis 15:208-12
Martin, Tammy M; Zhang, Zili; Kurz, Paul et al. (2009) The NOD2 defect in Blau syndrome does not result in excess interleukin-1 activity. Arthritis Rheum 60:611-8

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