Arkaitz Mucientes1, Ana Márquez2, Miguel Cordero-Coma3, José Manuel Martín-Villa4, Marina Begoña Gorroño-Echebarría5, Ricardo Blanco6, David Díaz Valle7, José Manuel Benítez-del-Castillo7, María José del Rio8, Ana Blanco9, Jose Luis Olea10, Yolanda Cordero11, María José Capella12, Jacobo Gonzalez13, Manuel Díaz-Llopis14, Norberto Ortego-Centeno15, Alfredo Adán16, Ioana Ruiz-Arruza17, Víctor Llorenç16, Alejandro Fonollosa18, Javier Martín1. 1. Instituto de Parasitología y Biomedicina López-Neyra, CSIC, Granada, Spain. 2. Instituto de Parasitología y Biomedicina López-Neyra, CSIC, Granada, Spain Systemic Autoimmune Diseases Unit, Hospital Clínico San Cecilio, Granada, Spain. 3. Ophthalmology Department, Hospital de León, IBIOMED, Universidad de León, León, Spain. 4. Immunology Department, Facultad de Medicina, Universidad Complutense de Madrid, Madrid, Spain. 5. Ophthalmology Department, Hospital Universitario Principe de Asturias, Alcalá de Henares, Spain. 6. Rheumatology Department, Hospital Marqués de Valdecilla, IDIVAL, Santander, Spain. 7. Ophthalmology Department, Hospital Clínico San Carlos, Madrid, Spain. 8. Ophthalmology Department, Hospital Carlos Haya, Málaga, Spain. 9. Ophthalmology Department, Hospital Donostia, San Sebastián (Guipúzcoa), Spain. 10. Ophthalmology Department, Hospital Son Espases, Palma de Mallorca, Spain. 11. Ophthalmology Department, Hospital Universitario Rio Hortega, Valladolid, Spain. 12. Institut Universitari Barraquer, Universitat Autònoma de Barcelona, Barcelona, Spain. 13. Ophthalmology Department, Hospital de la Princesa, Madrid, Spain. 14. Ophthalmology Department, Hospital La Fe, Universidad de Valencia, Valencia, Spain. 15. Systemic Autoimmune Diseases Unit, Hospital Clínico San Cecilio, Granada, Spain. 16. Ophthalmology Department, Hospital Clinic, Barcelona, Spain. 17. Autoimmune Diseases Research Unit, Internal Medicine Department, BioCruces Health Research Institute, Hospital Universitario Cruces, Barakaldo, Spain. 18. Ophthalmology Department, BioCruces Health Research Institute, Hospital Universitario Cruces, Barakaldo, Spain.
Abstract
BACKGROUND/AIMS: 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. SUBTITLE: 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. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.
BACKGROUND/AIMS: 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. SUBTITLE: 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. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.