Tumor necrosis factor polymorphisms associated with tumor necrosis factor production influence the risk of idiopathic intermediate uveitis.
Copyright policy )Tumor necrosis factor polymorphisms associated with tumor necrosis factor production influence the risk of idiopathic intermediate uveitis.
Idiopathic intermediate uveitis (IIU) is a potentially sight-threatening inflammatory disorder with well-defined anatomic diagnostic criteria. It is often associated with multiple sclerosis, and both conditions are linked to HLA-DRB1*15. Previously, we have shown that non-infectious uveitis (NIU) is associated with interleukin 10 (IL10) polymorphisms, IL10-2849A (rs6703630), IL10+434T (rs2222202), and IL10+504G (rs3024490), while a LTA+252AA/TNFA-238GG haplotype (rs909253/rs361525) is protective. In this study, we determined whether patients with IIU have a similar genetic profile as patients with NIU or multiple sclerosis.Twelve polymorphisms were genotyped, spanning the tumor necrosis factor (TNF) and IL10 genomic regions, in 44 patients with IIU and 92 population controls from the UK and the Republic of Ireland.IIU was strongly associated with the TNFA-308A and TNFA-238A polymorphisms. We found the combination of TNFA-308 and -238 loci was more strongly associated with IIU than any other loci across the major histocompatibility complex, including HLA-DRB1.TNF polymorphisms, associated with increased TNF production, are highly associated with IIU. These results offer the potential to ascribe therapeutic response and risk (i.e., the influence of HLA-DRB1*15 status and TNFR1 polymorphism) to anti-TNF therapy in IIU.
- University of Bristol United Kingdom
- Royal Victoria Eye and Ear Hospital Ireland
- Bristol Eye Hospital United Kingdom
- University of Aberdeen United Kingdom
- Trinity College Dublin Ireland
Adult, Male, Multiple Sclerosis, 610, DENDRITIC CELLS, Gene Frequency, Risk Factors, 616, Humans, Genetic Predisposition to Disease, Genetic Association Studies, Aged, Aged, 80 and over, Polymorphism, Genetic, FACTOR-ALPHA PROMOTER, Tumor Necrosis Factor-alpha, HUMAN-MONOCYTES, SINGLE-NUCLEOTIDE POLYMORPHISMS, ANTI-TNF THERAPY, MULTIPLE-SCLEROSIS, Middle Aged, MAJOR HISTOCOMPATIBILITY COMPLEX, Interleukin-10, Haplotypes, Receptors, Tumor Necrosis Factor, Type I, Case-Control Studies, FAMILIAL PARS PLANITIS, Female, EXPERIMENTAL AUTOIMMUNE UVEORETINITIS, Uveitis, Intermediate, CYTOKINE GENE POLYMORPHISM, HLA-DRB1 Chains
Adult, Male, Multiple Sclerosis, 610, DENDRITIC CELLS, Gene Frequency, Risk Factors, 616, Humans, Genetic Predisposition to Disease, Genetic Association Studies, Aged, Aged, 80 and over, Polymorphism, Genetic, FACTOR-ALPHA PROMOTER, Tumor Necrosis Factor-alpha, HUMAN-MONOCYTES, SINGLE-NUCLEOTIDE POLYMORPHISMS, ANTI-TNF THERAPY, MULTIPLE-SCLEROSIS, Middle Aged, MAJOR HISTOCOMPATIBILITY COMPLEX, Interleukin-10, Haplotypes, Receptors, Tumor Necrosis Factor, Type I, Case-Control Studies, FAMILIAL PARS PLANITIS, Female, EXPERIMENTAL AUTOIMMUNE UVEORETINITIS, Uveitis, Intermediate, CYTOKINE GENE POLYMORPHISM, HLA-DRB1 Chains
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