The genetic predictors of severe outcome in patients with anterior uveitis.
Doctoral thesis, UCL (University College London).
Uveitis is a generic term for a wide variety of different types of intraocular inflammation with different clinical phenotypes and visual outcomes. The explanation for why some patients develop chronic anterior disease whereas others do not is unknown. It seems likely that host factors such as the cytokine milieu of the aqueous humor may be an important factor in determining outcome. In turn, their secretion is genetically determined and cytokine gene polymorphisms have been associated with high or low level production whatever the stimulus. Purpose: The aim of this study was to identify key cytokine and chemokine polymorphisms associated with disease susceptibility, clinical phenotype, and development of visually significant complications in patients with anterior uveitis. Methods: PCR amplification was used to genotype a number of biallelic SNPs in several cytokine genes. This genetic data was then compared between patients and healthy controls, and within the patient group itself for association with clinical disease outcomes. Results: Our results show that a significant difference in the frequency of TNF-857T allele in patients with idiopathic anterior uveitis. We found a significant association between TNF-308 allele G and patients with anterior uveitis who were HLA-B27 positive. Patients with HLA-B27 associated anterior uveitis who developed visually threatening complications were more likely to carry the TNFRSF1A-201T or TNFRSF1A-1135T alleles. In addition, the frequency of IL- 1ra allele T was found to be significantly associated with chronicity of the disease. The frequency of MCP-1 (-2076T) allele was found to be significantly higher in healthy individuals when compared to patients with acute idiopathic anterior uveitis. Conclusions: These results suggest that genetic variations in proinflammatory mediators may influence the susceptibility and severity of the inflammatory response in eyes of patients with anterior uveitis. This knowledge may be useful in identifying prognosis and responsiveness to anti-TNF blockade in patients with anterior uveitis.
|Title:||The genetic predictors of severe outcome in patients with anterior uveitis|
|Open access status:||An open access version is available from UCL Discovery|
|Additional information:||Third party copyright material has been removed from the e-thesis.|
|UCL classification:||UCL > School of Life and Medical Sciences > Faculty of Brain Sciences > Institute of Ophthalmology|
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