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T.M. Martin, J.D. Reveille, T.M. Doyle, J.R. Smith, B. Rajska, M.D. Becker, R.D. Levinson, N.K. Wade, H.R. Schumacher, J.T. Rosenbaum; Familial Acute Anterior Uveitis: An HLA Analysis . Invest. Ophthalmol. Vis. Sci. 2003;44(13):2384.
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Purpose: Anterior uveitis with sudden onset is the most common form of uveitis and can be familial. This form of uveitis is highly associated with HLA-B27. In an effort to search for additional uveitis-susceptibility genes, families in which 2 or more members diagnosed with acute anterior uveitis (AAU) were recruited. Here we present HLA-B27 subtyping and HLA class II typing data on familial AAU. Methods: A total of 131 families with AAU from the U.S., Canada and Germany have been screened. Of these, 72 have been enrolled and 8 are in various stages of early enrollment. After careful review of ophthalmological records, 13 of the 72 families were withdrawn, leaving a total of 59 enrolled families. Members of 32 families have been typed at the HLA-B, -DRB1, -DQA and -DQB loci and are included in this analysis. Blood from AAU family members (both with and without uveitis) was obtained and DNA extracted using standard techniques. HLA-B typing was performed by SSCP with Dynal beads and HLA-B27 subtyping was by direct sequencing. HLA-DRB1, DQA1 and DQB1 typing was carried out by oligotyping and direct sequencing . Statistical analyses were performed by the Fisher's exact test. Results: From the 32 families, a total of 92 individuals (75 with AAU, ankylosing spondylitis, or both, and 17 unaffected) are of known HLA-B27 status (80 positive and 12 negative). Most specifically, 32 of 32 probands had HLA-B*2705, compared to 6% of 106 North American Caucasoid controls (p<1 x 10-8, RR=17.67) and 86% of 29 HLA-B27 positive controls (p=0.045). No differences in frequency were seen for other HLA-B locus alleles. For HLA class II analysis 90 individuals have been typed. When allele frequencies of those with AAU were compared to those without AAU, no statistically significant differences were noted. Only the differences in allele frequencies of DR7 approached statistical significance ( 3% with AAU compared to 11% without AAU, p=0.06). Conclusions: The high frequency of B*2705 is slightly larger than that reported for Caucasians in general (~90%). This study did not find any association between AAU and HLA class II DRB1, DQA or DQB. With these families and our continuing recruitment efforts we have established the largest cohort of familial AAU. Future studies will expand the search for uveitis genetic associations.
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