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A large multicentre analysis of CTGF −945 promoter polymorphism does not confirm association with systemic sclerosis susceptibility or phenotype
  1. B Rueda1,
  2. C Simeon2,
  3. R Hesselstrand3,
  4. A Herrick4,
  5. J Worthington4,
  6. N Ortego-Centeno5,
  7. G Riemekasten6,
  8. V Fonollosa2,
  9. M C Vonk7,
  10. F H J van den Hoogen8,
  11. J Sanchez-Román9,
  12. M A Aguirre-Zamorano10,
  13. R García-Portales11,
  14. A Pros12,
  15. M T Camps13,
  16. M A Gonzalez-Gay14,
  17. M F Gonzalez-Escribano15,
  18. M J Coenen16,
  19. N Lambert17,
  20. J L Nelson18,
  21. T R D J Radstake19,
  22. J Martin1
  1. 1
    Instituto de Parasitologia y Biomedicina “López-Neyra” (CSIC), Granada, Spain
  2. 2
    Servicio de Medinina Interna, Hospital Vall de Ebron, Barcelona, Spain
  3. 3
    Department of Rheumatology, Lund University Hospital, Lund, Sweden
  4. 4
    Rheumatic Diseases Centre, University of Manchester, Salford Royal NHS Foundation Trust, Manchester, UK
  5. 5
    Servicio de Medicina Interna, Hospital Clinico Universitario, Granada, Spain
  6. 6
    Department of Rheumatology and Clinical Immunology, Charité University Hospital, Berlin, Germany
  7. 7
    Department of Rheumatology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands
  8. 8
    Department of Rheumatology, Sint Maartenskliniek, Nijmegen, The Netherlands
  9. 9
    Servicio de Medicina Interna, Hospital Virgen del Rocio, Sevilla, Spain
  10. 10
    Servicio de Reumatología, Hospital Reina Sofía, Córdoba, Spain
  11. 11
    Servicio Medicina Interna, Hospital Virgen de la Victoria, Málaga, Spain
  12. 12
    Servicio de Reumatología, Hospital del Mar, Barcelona, Spain
  13. 13
    Servicio de Medicina Interna, Hospital Carlos Haya, Malaga, Spain
  14. 14
    Servicio de Reumatología, Hospital Xeral-Calde, Lugo, Spain
  15. 15
    Servicio de Inmunología, Hospital Virgen del Rocio, Sevilla, Spain
  16. 16
    Department of Human Genetics, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands
  17. 17
    INSERM U639, Parc scientifique de Luminy Marseille, Marseille, France
  18. 18
    Department of Medicine, University of Washington, Seattle, Washington, USA
  19. 19
    Department of Rheumatology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands
  1. Correspondence to Dr J Martin, Instituto de Parasitologia y Biomedicina “López-Neyra”, Consejo Superior de Investigaciones Científicas, Parque Tecnológico Ciencias de la Salud, Avenida del Conocimiento s/n 18100-Armilla, Granada, Spain; martin{at}ipb.csic.es

Abstract

Objective: To conduct a replication study to investigate whether the −945 CTGF genetic variant is associated with systemic sclerosis (SSc) susceptibility or specific SSc phenotype.

Methods: The study population comprised 1180 patients with SSc and 1784 healthy controls from seven independent case–control sets of European ancestry (Spanish, French, Dutch, German, British, Swedish and North American). The −945 CTGF genetic variant was genotyped using a Taqman 5′ allelic discrimination assay.

Results: An independent association study showed in all the case–control cohorts no association of the CTGF −945 polymorphism with SSc susceptibility. These findings were confirmed by a meta-analysis giving a pooled OR = 1.12 (95% CI 0.99 to 1.25), p = 0.06. Investigation of the possible contribution of the −945 CTGF genetic variant to SSc phenotype showed that stratification according to SSc subtypes (limited or diffuse), selective autoantibodies (anti-topoisomerase I or anticentromere) or pulmonary involvement reached no statistically significant skewing.

Conclusion: The results do not confirm previous findings and suggest that the CTGF −945 promoter polymorphism does not play a major role in SSc susceptibility or clinical phenotype.

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Footnotes

  • Funding This work was supported by grants SAF2009-11110, and in part by Junta de Andalucía, grupo CTS-180 and partially by RETICS Program, RD08/0075 (RIER) from Instituto de Salud Carlos III (ISCIII). TRDJR was supported by the VENI and VIDI laureates from the Dutch National Organisation of Research (NWO).

  • Competing interests None.

  • Ethics approval The study was approved by local ethics committees from all the participating centres.

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