Cytokine polymorphism in noninfectious uveitis

D Atan, S Fraser-Bell, J Plskova, L Kuffova, A Hogan, A Tufail, DJ Kilmartin, JV Forrester, J Bidwell, AD Dick, AJ Churchill

Research output: Contribution to journalArticle (Academic Journal)

35 Citations (Scopus)

Abstract

Purpose. Noninfectious uveitis is a sight-threatening immune-mediated intraocular inflammatory disorder. The inheritance of uveitis in multiplex families and its association with known monogenic and polygenic immunologic disorders suggests that common genetic variants underlie susceptibility to uveitis as well as to other immunologic disorders. TNFA and IL10 are strong candidate genes, given the influence of these cytokines on inflammation, immune tolerance, and apoptosis. Methods. The role of 12 polymorphisms spanning the TNFA and IL10 genomic regions was investigated in 192 uveitis patients and 92 population control subjects from four regional centers in the United Kingdom and Republic of Ireland. Results. The results demonstrate that uveitis is associated with three haplotype-tagging SNPs (htSNPs) in the IL10 gene: htSNP2 (rs6703630), htSNP5 (rs2222202), and htSNP6 (rs3024490). IL10htSNP2AG/htSNP5TC was the most significantly associated haplotype (P = 0.00085), whereas the LTA+252AA/TNFhtSNP2GG haplotype was protective (P = 0.00031). Furthermore, subgroup analysis showed that the frequency of the TNFd4 allele was higher in patients with nonremitting ocular disease and/or those requiring higher levels of maintenance immunosuppression. Although these associations lost significance after Bonferroni correction, they infer a relationship that may be validated by a larger study. Conclusions. Since these variants are implicated in the susceptibility and severity of several immunologic disorders, the results support the hypothesis that common genetic determinants influence shared mechanisms of autoimmunity.
Translated title of the contributionCytokine polymorphism in noninfectious uveitis
Original languageEnglish
Pages (from-to)4133 - 4142
Number of pages10
JournalInvestigative Ophthalmology and Visual Science
Volume51
Issue number8
DOIs
Publication statusPublished - Aug 2010

Bibliographical note

Other: Epub 2010 Mar 24

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    Atan, D., Fraser-Bell, S., Plskova, J., Kuffova, L., Hogan, A., Tufail, A., Kilmartin, DJ., Forrester, JV., Bidwell, J., Dick, AD., & Churchill, AJ. (2010). Cytokine polymorphism in noninfectious uveitis. Investigative Ophthalmology and Visual Science, 51(8), 4133 - 4142. https://doi.org/10.1167/iovs.09-4583