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Association of a non-synonymous functional variant of the ITGAM gene with systemic sclerosis
  1. F David Carmona1,
  2. Carmen P Simeon2,
  3. Lorenzo Beretta3,
  4. Patricia Carreira4,
  5. Madelon C Vonk5,
  6. Raquel Ríos-Fernández6,
  7. Gerard Espinosa7,
  8. Nuria Navarrete8,
  9. Esther Vicente-Rabaneda9,
  10. Luis Rodríguez-Rodríguez10,
  11. Carlos Tolosa11,
  12. Francisco J García-Hernández12,
  13. Iván Castellví13,
  14. María Victoria Egurbide14,
  15. Vicente Fonollosa2,
  16. Miguel A González-Gay15,
  17. Mónica Rodríguez-Carballeira16,
  18. Federico Díaz-Gónzalez17,
  19. Luis Sáez-Comet18,
  20. Roger Hesselstrand19,
  21. Gabriela Riemekasten20,
  22. Torsten Witte21,
  23. Alexandre E Voskuyl22,
  24. Annemie J Schuerwegh23,
  25. Rajan Madhok24,
  26. Paul Shiels24,
  27. Carmen Fonseca25,
  28. Christopher Denton25,
  29. Annika Nordin26,
  30. Øyvind Palm27,
  31. Anna-Maria Hoffmann-Vold27,
  32. Paolo Airó28,
  33. Raffaella Scorza3,
  34. Claudio Lunardi29,
  35. Jacob M van Laar30,
  36. Nicolas Hunzelmann31,
  37. Alexander Kreuter32,
  38. Ariane Herrick33,
  39. Jane Worthington33,
  40. Bobby P C Koeleman34,
  41. Timothy R D J Radstake5,
  42. Javier Martín1
  1. 1Instituto de Parasitología y Biomedicina López-Neyra, CSIC, Granada, Spain
  2. 2Department of Internal Medicine, Hospital Valle de Hebron, Barcelona, Spain
  3. 3Referral Center for Systemic Autoimmune Diseases, University of Milan, Milan, Italy
  4. 4Department of Rheumatology, Hospital 12 de Octubre, Madrid, Spain
  5. 5Department of Rheumatology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands
  6. 6Department of Internal Medicine, Hospital Clínico Universitario, Granada, Spain
  7. 7Department of Internal Medicine, Hospital Clínico de Barcelona, Barcelona, Spain
  8. 8Department of Internal Medicine, Hospital Virgen de las Nieves, Granada, Spain
  9. 9Department of Rheumatology, Hospital de la Princesa, Madrid, Spain
  10. 10Department of Rheumatology, Hospital Clinico San Carlos, Madrid, Spain
  11. 11Department of Internal Medicine, Hospital Parc Tauli, Sabadell, Spain
  12. 12Department of Internal Medicine, Hospital Virgen del Rocío, Sevilla, Spain
  13. 13Department of Rheumatology, Hospital de Sant Pau, Barcelona, Spain
  14. 14Department of Internal Medicine, Hospital de Cruces, Barakaldo, Spain
  15. 15Department of Rheumatology, Hospital Universitario Marqués de Valdecilla, IFIMAV, Santander, Spain
  16. 16Department of Internal Medicine, Hospital Universitari Mútua Terrassa, Barcelona, Spain
  17. 17Department of Rheumatology, Hospital Universitario de Canarias, Tenerife, Spain
  18. 18Department of Internal Medicine, Hospital Universitario Miguel Servet, Zaragoza, Spain
  19. 19Department of Rheumatology, Lund University, Lund, Sweden
  20. 20Department of Rheumatology and Clinical Immunology, Charité University Hospital, Berlin, Germany
  21. 21Hannover Medical School, Hannover, Germany
  22. 22Department of Rheumatology, VU University Medical Center, Amsterdam, The Netherlands
  23. 23Department of Rheumatology, Leiden University Medical Center, Leiden, The Netherlands
  24. 24University of Glasgow, Glasgow, UK
  25. 25Centre for Rheumatology, Royal Free and University College Medical School, London, UK
  26. 26Karolinska Institute, Stockholm, Sweden
  27. 27Department of Rheumatology, Rikshospitalet, Oslo University Hospital, Oslo, Norway
  28. 28Servizio di Reumatologia ed Immunologia Clinica Spedali Civili, Brescia, Italy
  29. 29Department of Medicine, Università degli Studi di Verona, Verona, Italy
  30. 30Institute of Cellular Medicine, Newcastle University, Newcastle, UK
  31. 31Department of Dermatology, University of Cologne, Cologne, Germany
  32. 32Ruhr University of Bochum, Bochum, Germany
  33. 33Arthritis Research UK Epidemiology Unit, University of Manchester, Manchester Academic Health Science Centre, Manchester, UK
  34. 34Department of Medical Genetics, University Medical Center Utrecht, Utrecht, The Netherlands
  1. Correspondence to F David Carmona, Instituto de Parasitología y Biomedicina López-Neyra, Consejo Superior de Investigaciones Científicas, Parque Tecnológico Ciencias de la Salud, Avenida del Conocimiento s/n 18100-Armilla, Granada, Spain; dcarmona{at}

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Systemic sclerosis (SSc) is a chronic fibrotic autoimmune disease of complex aetiology which shares genetic similarities with systemic lupus erythematosus (SLE).1 2 One of the novel risk loci that have been recently associated with SLE is the integrin α M (ITGAM) gene, which encodes the α subunit of the αMβ2-integrin.3 4 The most likely causal polymorphism that best explains this association is a non-synonymous single-nucleotide polymorphism (SNP) at the exon 3, rs1143679, which changes the 77th amino acid residue arginine to histidine (R77H). This functional SNP represents one of the highest associated signals with SLE and is predicted to alter the structure and function of the integrin.4 5 To determine whether ITGAM rs1143679 is also associated with SSc susceptibility and clinical manifestations, we genotyped a total of 3735 SSc patients and 3930 matched healthy individuals from seven independent European cohorts of Caucasian origin (Spain, Germany, The Netherlands, Italy, Norway, Sweden and UK) using a predesigned TaqMan® assay (ID: C___2847895_1_) in an ABI 7900HT (both from Applied Biosystems, Foster City, California, USA). Case …

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  • Funding This work was supported by GEN-FER from the Spanish Society of Rheumatology, SAF2009-11110 from the Spanish Ministry of Science, CTS-4977 and CTS-180 from junta de Andalucía, Orphan Disease program from EULAR, RETICS Program, RD08/0075 (RIER) from Instituto de Salud Carlos III (ISCIII), EUSTAR and the German Network of Systemic Sclerosis, VIDI laureate from the Dutch Association of Research (NWO) and Dutch Arthritis Foundation (National Reumafonds). TW was granted by DFG WI 1031/6.1. FDC was supported by Consejo Superior de Investigaciones Científicas (CSIC) through the programme JAE-DOC.

  • Patient consent Obtained.

  • Ethics approval Approvals were obtained from the local ethical committees of every participant centre.

  • Provenance and peer review Not commissioned; externally peer reviewed.