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Identification of the PTPN22 functional variant R620W as susceptibility genetic factor for giant cell arteritis
  1. A Serrano1,
  2. A Márquez1,
  3. S L Mackie2,
  4. F D Carmona1,
  5. R Solans3,
  6. J A Miranda-Filloy4,
  7. J Hernández-Rodríguez5,
  8. M C Cid5,
  9. S Castañeda6,
  10. IC Morado7,
  11. J Narváez8,
  12. R Blanco9,
  13. B Sopeña10,
  14. M J García-Villanueva11,
  15. J Monfort12,
  16. N Ortego-Centeno13,
  17. A Unzurrunzaga14,
  18. B Marí-Alfonso15,
  19. J Sánchez-Martín16,
  20. E de Miguel17,
  21. C Magro18,
  22. E Raya18,
  23. N Braun19,
  24. J Latus19,
  25. O Molberg20,
  26. B A Lie21,22,
  27. F Moosig23,
  28. T Witte24,
  29. A W Morgan2,
  30. M A González-Gay9,
  31. J Martín1,
  32. UK GCA Consortium Spanish GCA Consortium
  1. 1Instituto de Parasitología y Biomedicina López-Neyra, CSIC, Granada, Spain
  2. 2NIHR-Leeds Musculoskeletal Biomedical Research Unit, Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds, Leeds, West Yorkshire, UK
  3. 3Department of Internal Medicine, Hospital Vall d'Hebron, Barcelona, Spain
  4. 4Department of Rheumatology, Hospital Xeral-Calde, Lugo, Spain
  5. 5Department of Autoimmune and Systemic Diseases, Vasculitis Research Unit, Hospital Clinic, University of Barcelona, Centre de Recerca Biomèdica Cellex (IDIBAPS), Barcelona, Spain
  6. 6Department of Rheumatology, Hospital de la Princesa, IIS-Princesa, Madrid, Spain
  7. 7Department of Rheumatology, Hospital Clínico San Carlos, Madrid, Spain
  8. 8Department of Rheumatology, Hospital Universitario de Bellvitge-IDIBELL, L'Hospitalet de Llobregat, Barcelona, Spain
  9. 9Department of Rheumatology, Hospital Universitario Marqués de Valdecilla, IFIMAV, Santander, Spain
  10. 10Department of Internal Medicine, Complejo Hospitalario Universitario de Vigo, Spain
  11. 11Department of Rheumatology, Hospital Ramón y Cajal, Madrid, Spain
  12. 12Department of Rheumatology, Grup de recerca cel·lular en inflamació i cartílag. IMIM (Institut de Recerca Hospital del Mar), Barcelona, Spain
  13. 13Department of Internal Medicine, Hospital Clínico San Cecilio, Granada, Spain
  14. 14Department of Internal Medicine, Hospital de Galdakano, Vizcaya, Spain
  15. 15Department of Internal Medicine, Corporació Sanitaria Parc Taulí, Instituto Universitario Parc Taulí, UAB, Sabadell, Barcelona, Spain
  16. 16Department of Rheumatology, Hospital Universitario 12 de Octubre, Madrid, Spain
  17. 17Department of Rheumatology, Hospital Universitario de La Paz, Madrid, Spain
  18. 18Department of Rheumatology, Hospital Clínico Universitario San Cecilio, Granada, Spain
  19. 19Department of Internal Medicine, Division of Nephrology, Robert-Bosch-Hospital, Stuttgart, Germany
  20. 20Department of Rheumatology, Oslo University Hospital, Oslo, Norway and Institute of Clinical Medicine, University of Oslo, Oslo, Norway
  21. 21Department of Medical Genetics, University of Oslo and Oslo University Hospital, Oslo, Norway
  22. 22Department of Immunology, Oslo University Hospital and University of Oslo, Oslo, Norway
  23. 23Department of Clinical Immunology and Rheumatology, University of Luebeck, Bad Bramstedt, Germany
  24. 24Hannover Medical School, Hannover, Germany
  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 18016-Armilla (Granada), Spain; anamaort{at}


Objective To analyse the role of the PTPN22 and CSK genes, previously associated with autoimmunity, in the predisposition and clinical phenotypes of giant cell arteritis (GCA).

Methods Our study population was composed of 911 patients diagnosed with biopsy-proven GCA and 8136 unaffected controls from a Spanish discovery cohort and three additional independent replication cohorts from Germany, Norway and the UK. Two functional PTPN22 polymorphisms (rs2476601/R620W and rs33996649/R263Q) and two variants of the CSK gene (rs1378942 and rs34933034) were genotyped using predesigned TaqMan assays.

Results The analysis of the discovery cohort provided evidence of association of PTPN22 rs2476601/R620W with GCA (PFDR=1.06E-04, OR=1.62, CI 95% 1.29 to 2.04). The association did not appear to follow a specific GCA subphenotype. No statistically significant differences between allele frequencies for the other PTPN22 and CSK genetic variants were evident either in the case/control or in stratified case analysis. To confirm the detected PTPN22 association, three replication cohorts were genotyped, and a consistent association between the PTPN22 rs2476601/R620W variant and GCA was evident in the overall meta-analysis (PMH=2.00E-06, OR=1.51, CI 95% 1.28 to 1.79).

Conclusions Our results suggest that the PTPN22 polymorphism rs2476601/R620W plays an important role in the genetic risk to GCA.

  • Gene Polymorphism
  • Giant Cell Arteritis
  • Polymyalgia Rheumatica

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