title: Specific association of IL17A genetic variants with panuveitis.
abstract: OBJECTIVE
  A pathogenic role of Th17 cells in uveitis has become clear in recent years. Therefore, in the present study, we aimed to evaluate the possible influence of the IL17A locus on susceptibility to non-anterior uveitis and its main clinical subgroups.
  
  
  METHODS
  Five IL17A polymorphisms (rs4711998, rs8193036, rs3819024, rs2275913 and rs7747909), selected by tagging, were genotyped using TaqMan assays in 353 Spanish patients with non-anterior uveitis and 1851 ethnically matched controls.
  
  
  RESULTS
  The case/control analysis yielded a consistent association between two of the analysed genetic variants, rs8193036 and rs2275913, and the presence of panuveitis under a dominant model (pFDR=2.86E-03, OR=2.26, 95% CI 1.42 to 3.59 and pFDR=0.033, OR=1.83, 95% CI 1.13 to 2.97, respectively). Subsequently, a specific association of both polymorphisms with the diffuse form of the disease was evident in the subphenotype analysis when considering this same genetic model (panuveitis vs posterior and intermediate uveitis: rs8193036, p=0.020; rs2275913, p=0.038). Independent effects of rs8193036 and rs2275913 were observed by conditional regression analysis.
  
  
  CONCLUSIONS
  Polymorphisms within the IL17A locus show a novel association with panuveitis. Our data agree with the elevated levels of this cytokine that are found in patients with uveitis, supporting a crucial role of Th17 cells in this pathology.
  
  
  BACKGROUND
  Our results clearly evidenced the role of IL17A as a novel genetic risk factor for panuveitis, thus suggesting the implication of Th17 cells in the extensive inflammation of the uveal tract that occurs in this subtype of uveitis.
authors.affiliation: Instituto de Parasitología y Biomedicina López-Neyra, CSIC, Granada, Spain.
authors.forename: Arkaitz
authors.initials: A
authors.lastname: Mucientes
authors.affiliation: Instituto de Parasitología y Biomedicina López-Neyra, CSIC, Granada, Spain Systemic Autoimmune Diseases Unit, Hospital Clínico San Cecilio, Granada, Spain.
authors.forename: Ana
authors.initials: A
authors.lastname: Márquez
authors.affiliation: Ophthalmology Department, Hospital de León, IBIOMED, Universidad de León, León, Spain.
authors.forename: Miguel
authors.initials: M
authors.lastname: Cordero-Coma
authors.affiliation: Immunology Department, Facultad de Medicina, Universidad Complutense de Madrid, Madrid, Spain.
authors.forename: José Manuel
authors.initials: JM
authors.lastname: Martín-Villa
authors.affiliation: Ophthalmology Department, Hospital Universitario Principe de Asturias, Alcalá de Henares, Spain.
authors.forename: Marina Begoña
authors.initials: MB
authors.lastname: Gorroño-Echebarría
authors.affiliation: Rheumatology Department, Hospital Marqués de Valdecilla, IDIVAL, Santander, Spain.
authors.forename: Ricardo
authors.initials: R
authors.lastname: Blanco
authors.affiliation: Ophthalmology Department, Hospital Clínico San Carlos, Madrid, Spain.
authors.forename: David
authors.initials: D
authors.lastname: Díaz Valle
authors.affiliation: Ophthalmology Department, Hospital Clínico San Carlos, Madrid, Spain.
authors.forename: José Manuel
authors.initials: JM
authors.lastname: Benítez-del-Castillo
authors.affiliation: Ophthalmology Department, Hospital Carlos Haya, Málaga, Spain.
authors.forename: María José
authors.initials: MJ
authors.lastname: del Rio
authors.affiliation: Ophthalmology Department, Hospital Donostia, San Sebastián (Guipúzcoa), Spain.
authors.forename: Ana
authors.initials: A
authors.lastname: Blanco
authors.affiliation: Ophthalmology Department, Hospital Son Espases, Palma de Mallorca, Spain.
authors.forename: Jose Luis
authors.initials: JL
authors.lastname: Olea
authors.affiliation: Ophthalmology Department, Hospital Universitario Rio Hortega, Valladolid, Spain.
authors.forename: Yolanda
authors.initials: Y
authors.lastname: Cordero
authors.affiliation: Institut Universitari Barraquer, Universitat Autònoma de Barcelona, Barcelona, Spain.
authors.forename: María José
authors.initials: MJ
authors.lastname: Capella
authors.affiliation: Ophthalmology Department, Hospital de la Princesa, Madrid, Spain.
authors.forename: Jacobo
authors.initials: J
authors.lastname: Gonzalez
authors.affiliation: Ophthalmology Department, Hospital La Fe, Universidad de Valencia, Valencia, Spain.
authors.forename: Manuel
authors.initials: M
authors.lastname: Díaz-Llopis
authors.affiliation: Systemic Autoimmune Diseases Unit, Hospital Clínico San Cecilio, Granada, Spain.
authors.forename: Norberto
authors.initials: N
authors.lastname: Ortego-Centeno
authors.affiliation: Ophthalmology Department, Hospital Clinic, Barcelona, Spain.
authors.forename: Alfredo
authors.initials: A
authors.lastname: Adán
authors.affiliation: Autoimmune Diseases Research Unit, Internal Medicine Department, BioCruces Health Research Institute, Hospital Universitario Cruces, Barakaldo, Spain.
authors.forename: Ioana
authors.initials: I
authors.lastname: Ruiz-Arruza
authors.affiliation: Ophthalmology Department, Hospital Clinic, Barcelona, Spain.
authors.forename: Víctor
authors.initials: V
authors.lastname: Llorenç
authors.affiliation: Ophthalmology Department, BioCruces Health Research Institute, Hospital Universitario Cruces, Barakaldo, Spain.
authors.forename: Alejandro
authors.initials: A
authors.lastname: Fonollosa
authors.affiliation: Instituto de Parasitología y Biomedicina López-Neyra, CSIC, Granada, Spain.
authors.forename: Javier
authors.initials: J
authors.lastname: Martín
mesh_terms: D000328:Adult; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D060005:Genotyping Techniques; D006801:Humans; D020381:Interleukin-17 / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D015864:Panuveitis / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D060888:Real-Time Polymerase Chain Reaction; D058504:Th17 Cells / Q000473:pathology; D044465:White People
chemical_list: C508717:IL17A protein, human; D020381:Interleukin-17
keywords: Genetics; Immunology; Inflammation