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L. A. Bye, M. Stanford, R. Vaughan, J. R. Smith, J. T. Rosenbaum, N. Wade, F. Mackensen, G. R. Wallace, T. M. Martin; Genotype Analysis of Two Polymorphisms of the Autoimmune Susceptibility Gene CTLA-4, in an Acute Anterior Uveitis Cohort. Invest. Ophthalmol. Vis. Sci. 2008;49(13):1714.
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Cytotoxic T-lymphocyte antigen-4 (CTLA-4) is a key regulatory molecule in T cell biology, and polymorphisms in the gene have been associated with several autoimmune diseases, including Graves’ disease, and multiple sclerosis, which have ocular pathology as a disease component. We assessed two CTLA-4 polymorphisms in acute anterior uveitis (AAU), the most common form of immune-mediated uveitis.
This research was conducted under human subjects protocols approved by the OHSU and UK ethics committees. Genomic DNA was extracted from whole blood obtained from healthy controls and subjects with AAU. The diagnostic validation of AAU was based on ophthalmology chart review by JRS. Genotyping of the CTLA-4 -318C/T (rs5742909) and +49A/G (rs231775) snps was performed by SSP-PCR. A case-control analysis was employed using the Fishers exact test.
The AAU cohort consisted of 140 subjects (78 female, 62 male), with 133 identified Caucasian by self-report. Of the 140 with AAU, 76 were without history of ankylosing spondylitis (AS), while 58 had a diagnosis and the remaining 6 subjects were considered to have probable or early signs of AS. The healthy control cohort represented 92 subjects (54 female, 38 male), 81 of whom were Caucasian. The minor allele frequencies of CTLA-4 -318 and +49 were 8.9% and 42.1%, respectively, in the AAU group, and 4.9% and 36.4% in the healthy controls. Although we noted slightly higher minor allele frequencies of both snps in the AAU group, the differences were not statistically significant. The snp allele frequencies in the control group were in agreement with other published Caucasian cohorts. Furthermore, sub-analyses with only the Caucasian samples, or only the subjects without AS, and a haplotype analysis of the 2 snps, did not reveal any significant differences between the cases and controls.
These results do not provide evidence that CTLA-4 polymorphisms contribute to the genetic risk of AAU. The two snps that were analyzed are associated with several autoimmune diseases and thus were of interest in AAU.
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