title: Two functional variants of IRF5 influence the development of macular edema in patients with non-anterior uveitis.
abstract: 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Instituto de Parasitología y Biomedicina López-Neyra, IPBLN, CSIC, Granada, Spain.
authors.forename: Ana
authors.initials: A
authors.lastname: Márquez
authors.forename: María Carmen
authors.initials: MC
authors.lastname: Cénit
authors.forename: Miguel
authors.initials: M
authors.lastname: Cordero-Coma
authors.forename: Norberto
authors.initials: N
authors.lastname: Ortego-Centeno
authors.forename: Alfredo
authors.initials: A
authors.lastname: Adán
authors.forename: Alejandro
authors.initials: A
authors.lastname: Fonollosa
authors.forename: David
authors.initials: D
authors.lastname: Díaz Valle
authors.forename: Esperanza
authors.initials: E
authors.lastname: Pato
authors.forename: Ricardo
authors.initials: R
authors.lastname: Blanco
authors.forename: Joaquín
authors.initials: J
authors.lastname: Cañal
authors.forename: Manuel
authors.initials: M
authors.lastname: Díaz-Llopis
authors.forename: Enrique
authors.initials: E
authors.lastname: de Ramón
authors.forename: María José
authors.initials: MJ
authors.lastname: Del Rio
authors.forename: José Luis
authors.initials: JL
authors.lastname: García Serrano
authors.forename: Joseba
authors.initials: J
authors.lastname: Artaraz
authors.forename: José Manuel
authors.initials: JM
authors.lastname: Martín-Villa
authors.forename: Víctor
authors.initials: V
authors.lastname: Llorenç
authors.forename: Marina Begoña
authors.initials: MB
authors.lastname: Gorroño-Echebarría
authors.forename: Javier
authors.initials: J
authors.lastname: Martín
mesh_terms: D000328:Adult; D000483:Alleles; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D050835:Interferon Regulatory Factors / Q000235:genetics*; D015810:Linkage Disequilibrium; D016015:Logistic Models; D008269:Macular Edema / Q000150:complications / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D014606:Uveitis, Anterior / Q000150:complications*
chemical_list: C431713:IRF5 protein, human; D050835:Interferon Regulatory Factors