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N. Kuo, P.A. Lympany, V. Menezo, A.L. Lagan, R.M. du Bois, K.I. Welsh, S. Lightman; Polymorphisms of Tumor Necrosis Factor-, Lymphotoxin-, and Tumor Necrosis Factor-Receptor 1 & 2 Gene in Patients With Idiopathic Anterior Uveitis . Invest. Ophthalmol. Vis. Sci. 2003;44(13):4602.
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Purpose:To determine the correlation between the single nucleotide polymorphisms (SNPs) of the Tumor necrosis factor (TNF) -α, Lymphotoxin (LT) -α, and TNF-receptors (TNFR) genes and idiopathic acute anterior uveitis (IAU) Methods:Patients with IAU were identified, clinical phenotyped and a blood sample taken for HLA-B27 and genetic analysis. Of these 19 had a single episode of IAU and 38 had recurrent IAU. The mean age was 47.38 years (SD 14.42 years). Controls were ethnically matched. Sequence specific primers with 3’-end mismatches were used to identify the presence of specific allelic variants through PCR amplification. A total of 17 SNPs in TNF-α, LT-α, TNFR1 and TNFR2 genes were examined in this study. Results:There was a significant increase in the frequency of TNF-857A allele in IAU compared to control (14.9% vs 7.3%, p = 0.007, pc = 0.03). Frequencies of haplotype 4, containing A allele at nucleotide position -857, were significant increased in IAU as compared to control (14.9% vs 7.1%, p = 0.004, pc = 0.02, odds ratio 2.1, 95% confidence interval 1.7-2.7). Thirty-five of the 57 IAU patients (61.4%) were HLA-B27 positive. HLA-B27 was significantly associated with recurrent form of IAU (Χ2 = 7.3, p = 0.007). A higher ratio of the frequency of TNF-857A allele in was found in HLA-B27 (+) IAU (18.6%) compared with HLA-B27 (-) (9.1%) and control (7.2%). Among the IAU patients with posterior synechiae (PS), 60.0% of the individuals carried TNF-857A, compared with 21.3% of the individuals without PS (p = 0.022, pc = 0.11). Conclusions:This is the first study linking uveitis and its clinical manifestations to the polymorphisms of TNF-α, LT-α, TNFR1 and TNFR2 genes. A significant increase in the allelic frequency of TNF-857A was found in the patients with IAU, especially in HLA-B27 positive patients in this preliminary result. Genetic variations of these proinflammatory mediators and their receptors may influence the susceptibility and severity of the inflammatory response within the eye of idiopathic acute anterior uveitis
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