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.
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 uveitispatients 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.
Authors: Francesco Pichi; Paola Carrai; Sunil K Srivastava; Careen Y Lowder; Paolo Nucci; Piergiorgio Neri Journal: Int Ophthalmol Date: 2015-10-09 Impact factor: 2.031
Authors: Ming-ming Yang; Timothy Y Y Lai; Pancy O S Tam; Sylvia W Y Chiang; Carmen K M Chan; Fiona O J Luk; Tsz-Kin Ng; Chi-Pui Pang Journal: Mol Vis Date: 2012-07-11 Impact factor: 2.367
Authors: Philip C Robinson; Theodora A M Claushuis; Adrian Cortes; Tammy M Martin; David M Evans; Paul Leo; Pamela Mukhopadhyay; Linda A Bradbury; Katie Cremin; Jessica Harris; Walter P Maksymowych; Robert D Inman; Proton Rahman; Nigil Haroon; Lianne Gensler; Joseph E Powell; Irene E van der Horst-Bruinsma; Alex W Hewitt; Jamie E Craig; Lyndell L Lim; Denis Wakefield; Peter McCluskey; Valentina Voigt; Peter Fleming; Mariapia Degli-Esposti; Jennifer J Pointon; Michael H Weisman; B Paul Wordsworth; John D Reveille; James T Rosenbaum; Matthew A Brown Journal: Arthritis Rheumatol Date: 2015-01 Impact factor: 10.995
Authors: Denize Atan; Jarka Heissigerova; Lucia Kuffová; Aideen Hogan; Dara J Kilmartin; John V Forrester; Jeff L Bidwell; Andrew D Dick; Amanda J Churchill Journal: Mol Vis Date: 2013-01-28 Impact factor: 2.367