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Polymorphisms in the interleukin 4, interleukin 13 and corresponding receptor genes are not associated with systemic sclerosis and do not influence gene expression
  1. J C A Broen1,
  2. P Dieude2,
  3. M C Vonk1,
  4. L Beretta3,
  5. B Rueda4,
  6. A Herrick5,
  7. J Worthington5,
  8. N Hunzelmann6,
  9. G Riemekasten7,
  10. H Kiener8,
  11. R Scorza3,
  12. C P Simeon9,
  13. V Fonollosa9,
  14. (for the Spanish Systemic Sclerosis group),
  15. P Carreira10,
  16. N Ortego-Centeno11,
  17. M A Gonzalez-Gay12,
  18. P Airo'13,
  19. M J H Coenen14,
  20. A Aliprantis15,
  21. J Martin4,
  22. Y Allanore16,17,
  23. T R D J Radstake1
  1. 1Deparment of Rheumatology, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands
  2. 2Service de Rhumatologie, Université Diderot Paris 7, Paris, France
  3. 3Referral Center for Systemic Autoimmune Diseases, University of Milan, Milan, Italy
  4. 4Instituto de Parasitología y Biomedicina, CSIC, Granada, Spain
  5. 5Rheumatic Diseases Centre, University of Manchester, Salford Royal NHS Foundation Trust, Manchester, UK
  6. 6Department of Dermatology, University of Cologne, Cologne, Germany
  7. 7Department of Rheumatology and Clinical Immunology, Charité University Hospital and German Rheumatism Research Centre, a Leibniz institute, Berlin, Germany
  8. 8Department of Internal Medicine, Division of Rheumatology, University of Vienna, Vienna, Austria
  9. 9Servicio de Medicina Interna, Hospital Vall d'Hebron, Barcelona, Spain
  10. 10Servicio de Reumatologia, Hospital 12 de Octubre, Madrid, Spain
  11. 11Servicio de Medicina Interna, Hospital Xeral-Calde, Lugo, Spain
  12. 12Servicio de Reumatologia, Hospital Marques de Valdecillas, Santander, Spain
  13. 13Servizio di Reumatologia ed Immunologia Clinica, Spedali Civili, Brescia, Italy
  14. 14Department of Human Genetics, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands
  15. 15Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, Massachusetts, USA
  16. 16INSERM U781, Université Paris Descartes, Hôpital Necker, Paris, France
  17. 17Service de Rhumatologie A, Université Paris Descartes, Hôpital Cochin, Paris, France


Aim Polymorphisms in the interleukin 4 (IL-4), IL-13 and their corresponding receptors have previously been found associated with systemic sclerosis (SSc). In this study the authors aim to validate these previous observations and scrutinise their effects on gene expression.

Patients and methods The authors genotyped a cohort consisting of 2488 SSc patients and 2246 healthy controls, derived from The Netherlands, Spain, UK, Italy, Germany and France. Taqman assays were used for genotyping two single-nucleotide polymorphisms (SNPs) within IL-4 (Q576R/rs1801275) and the IL-4 α receptor (−590C/T/rs2243250). In the IL-13 gene two SNPs were genotyped R130Q (rs20541) and −1112C/T (rs1800925.) In the IL-13 α receptor gene, the 43163:G/A (rs6646259) variant was genotyped. In addition, the authors investigated the effect of these polymorphisms on corresponding gene expression with RT-PCR in B cells, T cells, plasmacytoid dendritic cells, monocytes and myeloid dendritic cells.

Results None of these polymorphisms was found to be enriched in the SSc population or in any SSc clinical subtype and there was no influence of these polymorphisms on development of either pulmonary arterial hypertension and declineer of forced vital capacity in 15 years of follow-up. In addition, the authors did not observe an effect on expression levels in the cell subtypes.

Conclusions This data show that these polymorphisms do not play a role in SSc and do not influence gene expression levels.

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