Two functional variants of IRF5 influence the development of macular edema in patients with non-anterior uveitis

• Published in: PloS one Vol. 8; no. 10; p. e76777
• Main Authors: Márquez, Ana, Cénit, María Carmen, Cordero-Coma, Miguel, Ortego-Centeno, Norberto, Adán, Alfredo, Fonollosa, Alejandro, Díaz Valle, David, Pato, Esperanza, Blanco, Ricardo, Cañal, Joaquín, Díaz-Llopis, Manuel, de Ramón, Enrique, Del Rio, María José, García Serrano, José Luis, Artaraz, Joseba, Martín-Villa, José Manuel, Llorenç, Víctor, Gorroño-Echebarría, Marina Begoña, Martín, Javier
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 07.10.2013; Public Library of Science (PLoS)
• Subjects: Adult; Alleles; Analysis; Autoimmune diseases; Autoimmunitat; Autoimmunity; Biological response modifiers; Care and treatment; Development and progression; Disease; Edema; Ethics; Female; Gene expression; Gene Frequency; Genetic aspects; Genetic diversity; Genetic markers; Genetic Predisposition to Disease - genetics; Genetic variance; Genotype; Haplotypes; Health risks; Hospitals; Humans; Interferon; Interferon regulatory factor; Interferon Regulatory Factors - genetics; Interferó; Internal medicine; Linkage Disequilibrium; Logistic Models; Lupus; Macular Edema - complications; Macular Edema - genetics; Male; Medical research; Middle Aged; Multiple sclerosis; Oftalmologia; Ophthalmology; Patients; Phenotype; Polymorphism, Single Nucleotide; Rheumatoid arthritis; Rheumatology; Uveitis; Uveitis, Anterior - complications; Spain
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0076777

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. 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. 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. 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.