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T.O. Missotten, V. Menezo, S.K. Bond, S. Liyanage, B. Baharlo, G.A. Wilson, S. Lightman; Interleukin–10 Promotor Polymorphism as a Geneic Predictor of Severe Outcome in Posterior Uveitis . Invest. Ophthalmol. Vis. Sci. 2004;45(13):3373.
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Purpose: Activated T Cells play an important role in the pathogenesis of uveitis. Th2 type cytokines, which include IL–10, have shown to inhibit Th1 cells and suppress inflammation. Production of IL–10 is under genetic control and it has been shown that adenine and guanine at the site –1082 in the promoter region are associated with low and high production of IL–10 respectively. The aim of this study was to determine the correlation between the IL–10 promoter polymorphism (–1082 G –> A) and the outcome of patients with non–infectious posterior uveitis. Methods: 49 patients with intraocular inflammation behind the lens–iris diaphragm of non–infectious origin were phenotyped and divided into those with idiopathic uveitis and uveitis associated to systemic disease. They were also divided according to the primary site of inflammation into intermediate, posterior and panuveitis. 98 ethnically matched controls were also genotyped. Total genomic DNA from peripheral citrated blood was extracted and IL–10 (–1082) G/A polymorphism was identified using TaqMan PCR. Results: We found an decrease of the IL–10 (–1082) A/A genotype in patients compared to controls (24.5% vs 41.9%, p<0.044). There was a significant increase of the IL–10 (–1082) G/G genotype frequency in patients who needed the addition of a second–line immunosuppressant agent in order to control their intraocular inflammation (on 2nd line agent : 50% of G/G vs 12.50% of A/A vs 25% of G/A , p=0.001). In addition to this, they also appeared to have a worse final visual outcome (Median VA : G/G LogMAR 0.4 vs A/A LogMAR 0.18 vs G/A LogMAR 0.18, and frequency of vision lower than LogMAR 1.0 : G/G (57.14%), A/A (14.29%), G/A (28.57%), p=0.005). However we did not find any association between the allele and genotype frequencies of the –1082 G/A polymorphism in the IL–10 gene promoter and the recurrence rate of uveitis. Conclusions: In this preliminary study we found that the IL–10 (–1082) G/G may contribute to the development of sight threatening complications, a more aggressive clinical course, or worse response to systemic corticosteroids in patients with chronic posterior uveitis. Genetic variations of this anti–inflammatory cytokine may partly explain the susceptibility and severity of the inflammatory process in patients with posterior uveitis.
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