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Are cytokine gene polymorphisms associated with outcome in patients with idiopathic intermediate uveitis in the United Kingdom?

M R Stanford¹, R W Vaughan², E Kondeatis², Y Chen¹, C E Edelsten³, E M Graham¹ and G R Wallace^1,4

¹ Departments of Ophthalmology, Guy’s, King’s and St Thomas’s Hospital Medical Schools, London, UK
² Clinical Transplantation Laboratory, Guy’s, King’s and St Thomas’s Hospital Medical Schools, London, UK
³ Department of Ophthalmology, Ipswich General Hospital, UK
⁴ Academic Unit of Ophthalmology, University of Birmingham, Birmingham, UK

Correspondence to:
Correspondence to:
Dr Graham Wallace
Academic Unit of Ophthalmology, Division of Immunity and Infection, University of Birmingham, Birmingham B15 2TT, UK; g.r.wallace{at}bham.ac.uk

Background/aim: Competing levels of cytokines, either locally within the eye or systemically, may influence the eventual outcome of ocular inflammation. Polymorphism in the promoter part of the genes controlling cytokine production may result in either higher or lower production of the relevant cytokine to a given stimulus. The authors hypothesised that such polymorphisms may relate to visual outcome in patients with idiopathic intermediate uveitis.

Methods: DNA was obtained from 125 patients with idiopathic intermediate uveitis and analysed for the interleukin 10 IL-10–1082G/A and IL-10–819C/T, and interferon IFN 874T/A gene polymorphisms. Associations with disease were calculated by both allelic frequency and haplotype analysis, and associations between ocular disease outcomes and the presence of polymorphisms were identified. A bad outcome was defined as loss of vision <6/12 Snellen in both eyes at 5 years from presentation when the eyes were quiet.

Results: An initial screen showed that the 874T allele of the IFN gene was more prevalent in patients than controls (² = 7.9; p = 0.004 OR 1.7; 95% CI 1.2 to 2.6 (Pc = 0.02), whereas the IL-10-1082/–819 AT haplotype of the interleukin 10 (IL-10) gene was not. Analysis of disease outcome showed an association between IL-10–1082 AA homozygosity and bad outcome (² = 13; p = 0.0003). Moreover, the two cytokine polymorphisms taken together showed that up to 75% of patients with a poor visual outcome had the combined IFN 874TA or TT genotype together with the IL-10–1082AA genotype (² = 13.2 p = 0.0008 OR 6.4; 95% CI 1.85 to 23.6 Pc = 0.1).

Conclusion: These results show that disease outcome in intermediate uveitis may be partly determined by a complex interplay between cytokine genes and these results may have implications for future treatment with biological agents that target these cytokines.

Abbreviations: EAU, experimental autoimmune uveitis; IFN, interferon gamma; IL-10, interleukin 10; PCR, polymerase chain reaction; SNP, single nucleotide polymorphism

Keywords: uveitis; cytokine; gene polymorphism

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