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Y. El–Shabrawi, B.J. Wegscheider, J. Hermann, U. Posch, M. Weger; TNF Alpha Promoter Gene Polymorphism in HLA B27 Associated Uveitis . Invest. Ophthalmol. Vis. Sci. 2005;46(13):3481.
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Purpose: HLA B27 associated uveitis is among the most common forms of anterior uveitis. So far the clear pathomechanism remains elusive. As a potentially polygenic disease, other genetic factors are likely to contribute to the disease. In this context attention has been focused on the relevance of TNF a promoter polymorphisms. Three of these, –488, –308 and –238 are located in the promoter region. The –308 G/A transition, is strongly associated with the development of SLE in Caucasians. The 238 SNP has also been reported to be associated with a number of autoimmune diseases, independent of HLA–association. In the present study we evaluated the presence of three, namely –488, –308, –276, of the TNFa gene polymorphisms in HLA B27 associated uveitis and in control populations. Material and Methods: 114 Caucasian patients suffering from an HLA B27 associated uveitis were included into the study. The mean age of the patients was 44.9 years. The mean duration of the disease was 115.6 month. Eighty–six patients (75.4%) suffered from an additional systemic manifestation of the disease. Sixty–three unrelated HLA B27 positive healthy blood donors, and 88 HLA B27 unrelated negative healthy individuals served as controls. Results: We found a significant decrease in the 238 and 308 gene promoter polymorphism in patients with an HLA B27 associated uveitis. A G/A mutation of the 238 promoter was seen in none of the uveitis patients. In the control groups (HLA B positive and HLA B27 negative) a SNP was seen in 4 (6.3%) patients (p = 0.015) and 7 (8.0%) patients (p = 0.003) respectively. No difference was seen in the distribution of the –488 G/A SNP among the various groups (p = 0.1). Uveitis patients with a G/A polymorphism of the 308 nucleotide showed a tendency towards a later onset of the disease (p = 0.09) than those with the wild type. Those patients, that however had a G/A polymorphism of the –488 nucleotide, did show a significantly more often chronic uveitis (p=0.007), than those patients with a HLA B27 positive uveitis, lacking this polymorphism. Conclusions: This data indicates that mutations in the TNFa promoter influence the susceptibility towards development of an intraocular inflammation in HLA B27 positive individuals.
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