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Influence of the IL17A locus in giant cell arteritis susceptibility
  1. A Márquez1,
  2. J Hernández-Rodríguez2,
  3. M C Cid2,
  4. R Solans3,
  5. S Castañeda4,
  6. M E Fernández-Contreras5,
  7. M Ramentol3,
  8. I C Morado6,
  9. J Narváez7,
  10. C Gómez-Vaquero7,
  11. V M Martínez-Taboada8,
  12. N Ortego-Centeno9,
  13. B Sopeña10,
  14. J Monfort11,
  15. M J García-Villanueva12,
  16. L Caminal-Montero13,
  17. E de Miguel14,
  18. R Blanco8,
  19. Spanish GCA Consortium,
  20. O Palm15,
  21. O Molberg15,
  22. J Latus16,
  23. N Braun16,
  24. F Moosig17,
  25. T Witte18,
  26. L Beretta19,
  27. A Santaniello19,
  28. G Pazzola20,
  29. L Boiardi20,
  30. C Salvarani20,
  31. M A González-Gay8,
  32. J Martín1
  1. 1Instituto de Parasitología y Biomedicina López-Neyra, CSIC, Granada, Spain
  2. 2Vasculitis Research Unit, Department of Autoimmune and Systemic Diseases, Hospital Clinic, University of Barcelona, Centre de Recerca Biomèdica Cellex (IDIBAPS), Barcelona, Spain
  3. 3Department of Internal Medicine, Hospital Vall d'Hebron, Barcelona, Spain
  4. 4Department of Rheumatology, Hospital de la Princesa, IIS-Princesa, Madrid, Spain
  5. 5Department of Pathology, Hospital de la Princesa, IIS-Princesa, Madrid, Spain
  6. 6Department of Rheumatology, Hospital Clínico San Carlos, Madrid, Spain
  7. 7Department of Rheumatology, Hospital Universitario de Bellvitge-IDIBELL, L'Hospitalet de Llobregat, Barcelona, Spain
  8. 8Department of Rheumatology, Hospital Universitario Marqués de Valdecilla, IFIMAV, Santander, Spain
  9. 9Department of Internal Medicine, Hospital Clínico San Cecilio, Granada, Spain
  10. 10Department of Internal Medicine, Complejo Hospitalario Universitario de Vigo, Pontevedra, Vigo, Spain
  11. 11Department of Rheumatology, Grup de recerca cel·lular en inflamació i cartílag, IMIM (Institut de Recerca Hospital del Mar), Barcelona, Spain
  12. 12Department of Rheumatology, Hospital Ramón y Cajal, Madrid, Spain
  13. 13Department of Internal Medicine, Hospital Universitario Central de Asturias, Oviedo, Spain
  14. 14Department of Rheumatology, Hospital Universitario La Paz, Madrid, Spain
  15. 15Department of Rheumatology, Rikshospitalet, Oslo University Hospital, Oslo, Norway
  16. 16Department of Internal Medicine, Division of Nephrology, Robert-Bosch-Hospital, Stuttgart, Germany
  17. 17Department of Clinical Immunology and Rheumatology, University of Luebeck, Bad Bramstedt, Germany
  18. 18Hannover Medical School, Hannover, Germany
  19. 19Referral Center for Systemic Autoimmune Diseases, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico di Milano, Milan, Italy
  20. 20Unita` Operativa di Reumatologia, Azienda Ospedaliera ASMN, Istituto di Ricovero e Cura a Carattere Scientifico, Reggio Emilia, Italy
  1. Correspondence to Dr Ana Márquez, Instituto de Parasitología y Biomedicina López-Neyra, Consejo Superior de Investigaciones Científicas, Parque Tecnológico Ciencias de la Salud, Avenida del Conocimiento s/n, Armilla (Granada) 18016, Spain; anamaort{at}ipb.csic.es

Abstract

Objective Different lines of evidence have highlighted the role of IL-17A in the inflammatory process occurring in giant cell arteritis (GCA). The aim of the present study was to assess whether the IL17A locus influences GCA susceptibility and its clinical subphenotypes.

Methods We carried out a large meta-analysis including a total of 1266 biopsy-proven GCA patients and 3779 healthy controls from four European populations (Spain, Italy, Germany and Norway). Five IL17A polymorphisms (rs4711998, rs8193036, rs3819024, rs2275913 and rs7747909) were selected by tagging and genotyped using TaqMan assays. Allelic combination and dependency tests were also performed.

Results In the pooled analysis, two of the five analysed polymorphisms showed evidence of association with GCA (rs2275913: PMH=1.85E−03, OR=1.17 (1.06–1.29); rs7747909: PMH=8.49E–03, OR=1.15 (1.04–1.27)). A clear trend of association was also found for the rs4711998 variant (PMH=0.059, OR=1.11 (1.00–1.23)). An independent effect of rs2275913 and rs4711998 was evident by conditional regression analysis. In addition, the haplotype harbouring the risk alleles better explained the observed association than the polymorphisms independently (likelihood p value <10−05).

Conclusions Polymorphisms within the IL17A locus show a novel association with GCA. This finding supports the relevant role of the Th17 cells in this vasculitis pathophysiology.

  • Giant Cell Arteritis
  • Gene Polymorphism
  • Cytokines

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