Analysis of the influence of PTPN22 gene polymorphisms in systemic sclerosis (original) (raw)

Clinical and epidemiological research

Analysis of the influence of PTPN22 gene polymorphisms in systemic sclerosis

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  1. LM Diaz-Gallo1,
  2. P Gourh2,
  3. J Broen3,
  4. C Simeon4,
  5. V Fonollosa4,
  6. N Ortego-Centeno5,
  7. S Agarwal2,
  8. MC Vonk3,
  9. M Coenen6,
  10. G Riemekasten7,
  11. N Hunzelmann8,
  12. R Hesselstrand9,
  13. FK Tan2,
  14. JD Reveille2,
  15. S Assassi2,
  16. FJ García-Hernandez10,
  17. P Carreira11,
  18. MT Camps12,
  19. A Fernandez-Nebro13,
  20. P Garcia de la Peña14,
  21. T Nearney15,
  22. D Hilda16,
  23. MA González-Gay17,
  24. P Airo18,
  25. L Beretta19,
  26. R Scorza19,
  27. A Herrick20,
  28. J Worthington20,
  29. A Pros21,
  30. I Gómez-Gracia22,
  31. L Trapiella23,
  32. G Espinosa24,
  33. I Castellvi25,
  34. T Witte26,
  35. F de Keyser27,
  36. M Vanthuyne28,
  37. MD Mayes2,
  38. TRDJ Radstake3,
  39. FC Arnett2,
  40. J Martin1,
  41. B Rueda1
  42. 1Instituto de Parasitología y Biomedicina Lopez-Neyra CSIC, Granada, Spain
  43. 2Department of Internal Medicine, Division of Rheumatology and Clinical Immunogenetics, The University of Texas Health Science Center at Houston Medical School, Houston, USA
  44. 3Department of Rheumatology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands
  45. 4Servicio de Medicina Interna, Hospital Valle de Hebron, Barcelona, Spain
  46. 5Servicio de Medicina Interna, Hospital Clinico Universitario, Granada, Spain
  47. 6Departmentof Human Genetics, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands
  48. 7Department of Rheumatology and Clinical Immunology, Charité University Hospital, Berlin, Germany
  49. 8Department of Dermatology, University of Cologne, Germany
  50. 9Department of Rheumatology, Lund University Hospital, Lund, Sweden
  51. 10Servicio de Medicina Interna, Hospital Virgen del Rocio, Sevilla, Spain
  52. 11Servicio de Reumatología, Hospital 12 de Octubre, Madrid, Spain
  53. 12Servicio de Medicina Interna, Hospital Carlos Haya, Málaga, Spain
  54. 13Servicio de Reumatología, Hospital Carlos Haya, Málaga, Spain
  55. 14Servicio de Reumatología, Hospital Ramon y Cajal, Madrid, Spain
  56. 15University of Texas Medical Branch at Galveston, Galveston, Texas, USA
  57. 16The University of Texas Health Science Center, San Antonio, Texas, USA
  58. 17Servicio de Reumatología, Hospital Marqués de Valdecilla, Santander, Spain
  59. 18Servizio di Reumatologia ed Immunologia Clinica Spedali Civili, Brescia, Italy
  60. 19Referral Center for Systemic Autoimmune Diseases, University of Milan, Milan, Italy
  61. 20Rheumatic Diseases Centre, University of Manchester, Salford Royal NHS Foundation Trust, UK
  62. 21Servicio de Reumatología, Hospital del Mar, Barcelona, Spain
  63. 22Servicio de Reumatología, Hospital Reina Sofía, Córdoba, Spain
  64. 23Servicio de Medicina Interna, Hospital Universitario Central de Asturias, Oviedo, Spain
  65. 24Servicio de Medicina Interna, Hospital Clinico, Barcelona, Spain
  66. 25Servicio de Reumatología, Hospital de Sant Pau, Barcelona, Spain
  67. 26Hannover Medical School, Hannover, Germany
  68. 27 Department of Rheumatology, University of Ghent, Belgium
  69. 28Department of Rheumatology, Université Catholique de Louvain, Belgium
  70. Correspondence to Dr Blanca Rueda, Instituto de Parasitología y Biomedicina ‘López-Neyra’, Consejo Superior deInvestigaciones Científicas, Parque Tecnológico Ciencias de la Salud, Avenida delConocimiento s/n, 18100-Armilla, Granada, Spain; blarume{at}ugr.es

Abstract

Objective Two functional single nucleotide polymorphisms (SNP) in the PTPN22 gene (rs24746601 and rs33996649) have been associated with autoimmunity. The aim of this study was to investigate the role of the R263Q SNP for the first time and to re-evaluate the role of the R620W SNP in the genetic predisposition to systemic sclerosis (SSc) susceptibility and clinical phenotypes.

Methods 3422 SSc patients (2020 with limited cutaneous SSc and 1208 with diffuse cutaneous SSc) and 3638 healthy controls of Caucasian ancestry from an initial case--control set of Spain and seven additional independent replication cohorts were included in our study. Both rs33996649 and rs2476601 PTPN22 polymorphisms were genotyped by TaqMan allelic discrimination assay. A meta-analysis was performed to test the overall effect of these PTPN22 polymorphisms in SSc.

Results The meta-analysis revealed evidence of association of the rs2476601 T allele with SSc susceptibility (pFDRcorrected=0.03 pooled, OR 1.15, 95% CI 1.03 to 1.28). In addition, the rs2476601 T allele was significantly associated with anticentromere-positive status (pFDRcorrected=0.02 pooled, OR 1.22, 95% CI 1.05 to 1.42). Although the rs33996649 A allele was significantly associated with SSc in the Spanish population (pFDRcorrected=0.04, OR 0.58, 95% CI 0.36 to 0.92), this association was not confirmed in the meta-analysis (p=0.36 pooled, OR 0.89, 95% CI 0.72 to 1.1).

Conclusion The study suggests that the PTPN22 R620W polymorphism influences SSc genetic susceptibility but the novel R263Q genetic variant does not. These data strengthen evidence that the R620W mutation is a common risk factor in autoimmune diseases.

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