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AB0003 A mif promoter polymorphism is associated with the susceptibility to pulmonary arterial hypertension in diffuse cutaneous systemic sclerosis patients
  1. E Lόpez-Isac1,
  2. L Bossini-Castillo1,
  3. D Campillo-Davό1,
  4. FD Carmona1,
  5. CP Simeόn2,
  6. P Carreira3,
  7. JL Callejas-Rubio4,
  8. I Castellví5,
  9. A Fernández-Nebro6,
  10. L Rodríguez-Rodríguez7,
  11. M Rubio Rivas8,
  12. FJ Hernández García9,
  13. AB Madroñero10,
  14. S Scleroderma Group1,
  15. L Beretta11,
  16. A Santaniello11,
  17. C Lunardi12,
  18. P Airό13,
  19. A-M Hoffmann-Vold14,
  20. A Kreuter15,
  21. G Riemekasten16,
  22. T Witte17,
  23. N Hunzelmann18,
  24. MC Vonk19,
  25. AE Voskuyl20,
  26. JDV Bouwstra21,
  27. P Shiels22,
  28. A Herrick23,
  29. J Worthington23,
  30. TRDJ Radstake24,
  31. J Martin1
  1. 1Biología Celular e Inmunología, Instituto de Parasitología y Biomedicina Lόpez Neyra (CSIC)., Armilla (Granada)
  2. 2Department of Internal Medicine, Hospital Valle de Hebrόn, Barcelona
  3. 3Department of Rheumatology, Hospital Universitario 12 de Octubre, Madrid
  4. 4Unidad de Enfermedades Sistémicas Autoinmunes, Department of Internal Medicine, Hospital Clínico Universitario San Cecilio, Granada
  5. 5Department of Rheumatology, Hospital de la Santa CreuiSant Pau, Barcelona
  6. 6Department of Rheumatology, Hospital Carlos Haya, Málaga
  7. 7Department of Rheumatology, Hospital Clínico San Carlos, Madrid
  8. 8Department of Internal Medicine, Hospital Universitario de Bellvitge, Barcelona
  9. 9Department of Internal Medicine, Hospital Virgen del Rocio, Sevilla
  10. 10Department of Internal Medicine, Hospital General San Jorge, Huesca, Spain
  11. 11Referral Center for Systemic Autoimmune Diseases, Fondazione IRCCS Ca' GrandaOspedale Maggiore Policlinico and University of Milan, Milán
  12. 12Department of Medicine, UniversitadegliStudi di Verona, Verona
  13. 13Servizio di Reumatologia ed Immunologia, Clinica Spedali Civili, Brescia, Italy
  14. 14Department of Rheumatology, Rikshospitalet, Oslo University Hospital, Oslo, Norway
  15. 15Department of Dermatology, Josefs-Hospital, Ruhr University Bochum, Bochum
  16. 16Clinic of Rheumatology, University of Lübeck, Lübeck
  17. 17Klinik fürImmunologie und Rheumatologie, Hannover Medical School, Hannover
  18. 18Department of Dermatology, University of Cologne, Cologne, Germany
  19. 19Department of Rheumatology, Radboud University Nijmegen Medical Centre, Nijmegen
  20. 20VU University Medical Center, Amsterdam
  21. 21Department of Rheumatology, Leiden University Medical Center, Leiden, Netherlands
  22. 22Glasgow Biomedical Research Centre, University of Glasgow, Glasgow
  23. 23Arthritis Research UK Epidemiology Unit, The University of Manchester, Manchester Academic Health Science Centre, Manchester, United Kingdom
  24. 24Department of Rheumatology & Clinical Immunology, University Medical Center Utrecht, Utrecht, Netherlands


Background Systemic sclerosis (SSc) is a fibrotic immune-mediated disease of unknown etiology. Among its clinical manifestations, pulmonary involvement is the leading cause of mortality in SSc patients. However, the genetic factors involved in lung complication are not well-defined.

Objectives We aimed to revisit the association of the MIF gene, which encodes a cytokine implicated in idiopathic pulmonary hypertension among other diseases, with the susceptibility and clinical expression of SSc, besides testing the association of this polymorphism with SScrelated pulmonary involvement.

Methods A total of 4,393SSc patients and 16,591 unaffected controls from six cohorts of European origin were genotyped for the MIF promoter variant rs755622. An inverse variance method was used to meta-analyze the data.

Results A statistically significant increase of the MIF rs755622*C allele frequency compared to controls was observed in the subgroups of patients with diffuse cutaneous SSc (dcSSc) and with pulmonary arterial hypertension (PAH) independently (dcSSc: P=3.20E-2, OR=1.13; PAH: P=2.19E-02, OR=1.32). However, our data revealed a stronger effect size with the subset of SSc patients showing both clinical manifestations (dcSSc with PAH: P=6.91E-3, OR=2.05).

Conclusions We revisited the association of the MIF rs755622*C allele with SSc and described a phenotype-specific association of this variant with the susceptibility to develop PAH in dSSc patients.

Disclosure of Interest None declared

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