Márquez, AnaCénit, María CarmenCordero-Coma, MiguelOrtego-Centeno, NorbertoAdán, AlfredoFonollosa, AlejandroDíaz Valle, DavidPato, EsperanzaBlanco, RicardoCañal, JoaquínDíaz-Llopis, ManuelRamón, Enrique, deRio, María José, delGarcía Serrano, José LuisArtaraz, JosebaMartín-Villa, José ManuelLlorenç, VíctorGorroño-Echebarría, Marina BegoñaMartín, Javier2015-08-062015-08-062013-10Márquez A, Cénit MC, Cordero-Coma M, Ortego-Centeno N, Adán A, Fonollosa A, et al. Two functional variants of IRF5 influence the development of macular edema in patients with non-anterior uveitis. PLoS ONE. 2013, 8(10):e76777http://hdl.handle.net/10668/1950Journal Article;OBJECTIVE Interferon (IFN) signaling plays a crucial role in autoimmunity. Genetic variation in interferon regulatory factor 5 (IRF5), a major regulator of the type I interferon induction, has been associated with risk of developing several autoimmune diseases. In the current study we aimed to evaluate whether three sets of correlated IRF5 genetic variants, independently associated with SLE and with different functional roles, are involved in uveitis susceptibility and its clinical subphenotypes. METHODS Three IRF5 polymorphisms, rs2004640, rs2070197 and rs10954213, representative of each group, were genotyped using TaqMan® allelic discrimination assays in a total of 263 non-anterior uveitis patients and 724 healthy controls of Spanish origin. RESULTS A clear association between two of the three analyzed genetic variants, rs2004640 and rs10954213, and the absence of macular edema was observed in the case/control analysis (P FDR =5.07E-03, OR=1.48, CI 95%=1.14-1.92 and P FDR =3.37E-03, OR=1.54, CI 95%=1.19-2.01, respectively). Consistently, the subphenotype analysis accordingly with the presence/absence of this clinical condition also reached statistical significance (rs2004640: P=0.037, OR=0.69, CI 95%=0.48-0.98; rs10954213: P=0.030, OR=0.67, CI 95%=0.47-0.96), thus suggesting that both IRF5 genetic variants are specifically associated with the lack of macular edema in uveitis patients. CONCLUSION Our results clearly showed for the first time that two functional genetic variants of IRF5 may play a role in the development of macular edema in non-anterior uveitis patients. Identifying genetic markers for macular edema could lead to the possibility of developing novel treatments or preventive therapies.enFactores reguladores del interferónUveítis anteriorDesequilibrio de ligamientoEdema macularModelos logísticosFenotipoPolimorfismo de nucleótido simpleMedical Subject Headings::Phenomena and Processes::Genetic Phenomena::Genetic Structures::Genome::Genome Components::Genes::AllelesMedical Subject Headings::Check Tags::FemaleMedical Subject Headings::Phenomena and Processes::Genetic Phenomena::Gene FrequencyMedical Subject Headings::Phenomena and Processes::Genetic Phenomena::Genotype::Genetic Predisposition to DiseaseMedical Subject Headings::Phenomena and Processes::Genetic Phenomena::GenotypeMedical Subject Headings::Phenomena and Processes::Genetic Phenomena::Genotype::HaplotypesMedical Subject Headings::Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::HumansMedical Subject Headings::Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Peptides::Intracellular Signaling Peptides and Proteins::Adaptor Proteins, Signal Transducing::Interferon Regulatory FactorsMedical Subject Headings::Phenomena and Processes::Genetic Phenomena::Genetic Linkage::Linkage DisequilibriumMedical Subject Headings::Health Care::Health Care Quality, Access, and Evaluation::Quality of Health Care::Health Care Evaluation Mechanisms::Statistics as Topic::Models, Statistical::Logistic ModelsMedical Subject Headings::Diseases::Eye Diseases::Retinal Diseases::Retinal Degeneration::Macular Degeneration::Macular EdemaMedical Subject Headings::Check Tags::MaleMedical Subject Headings::Named Groups::Persons::Age Groups::Adult::Middle AgedMedical Subject Headings::Phenomena and Processes::Genetic Phenomena::PhenotypeMedical Subject Headings::Phenomena and Processes::Genetic Phenomena::Genetic Variation::Polymorphism, Genetic::Polymorphism, Single NucleotideMedical Subject Headings::Diseases::Eye Diseases::Uveal Diseases::Uveitis::Panuveitis::Uveitis, AnteriorMedical Subject Headings::Named Groups::Persons::Age Groups::Adultresearch article24116155open access10.1371/journal.pone.00767771932-6203PMC3792064