Article Text

This article has a correction. Please see:

other Versions

BANK1 functional variants are associated with susceptibility to diffuse systemic sclerosis in Caucasians
  1. B Rueda1,*,
  2. P Gourh2,
  3. J Broen3,
  4. S K Agarwal4,
  5. C P Simeón5,
  6. N Ortego-Centeno6,
  7. M C Vonk7,
  8. M Coenen7,
  9. G Riemekasten8,
  10. N Hunzelmann9,
  11. R Hesselstrand10,
  12. F K Tan2,
  13. J D Reveille2,
  14. S Assasi2,
  15. F J Garcia-Hernandez11,
  16. P Carreira12,
  17. M Camps13,
  18. A Fernandez-Nebro14,
  19. P Garcia de la Peña15,
  20. T Nearney16,
  21. D Hilda17,
  22. M A Gónzalez-Gay18,
  23. P Airo19,
  24. L Beretta20,
  25. R Scorza20,
  26. T RDJ Radstake3,
  27. M Mayes2,
  28. F C Arnett21,
  29. J Martin1
  1. 1 CSIC, Spain;
  2. 2 University of Houston, Texas, United States;
  3. 3 Department of Rheumatology, Radboud University Nijmegen Medical Centre, Netherlands;
  4. 4 The University of Texas Health Science Center Houston Medical School, United States;
  5. 5 Hospital Vall d'Hebron, Spain;
  6. 6 Servicio de Medicina Interna, Hospital Clinico Universitario, Spain;
  7. 7 Radboud University Nijmegen Medical Centre, Netherlands;
  8. 8 Charité University Hospital, Netherlands;
  9. 9 Department of Dermatology, University of Cologne, Germany;
  10. 10 Department of Rheumatology, Lund University Hospital, S-221 85 Lund, Germany;
  11. 11 Servicio de Medicina Interna, Hospital Virgen del Rocio, Sweden;
  12. 12 Servicio de Reumatología, Hospital 12 de Octubre, United States;
  13. 13 Servicio de Medicina Interna, Hospital Carlos Haya, United States;
  14. 14 Servicio de Reumatologia, Hospital Carlos Haya, United States;
  15. 15 Servicio de Reumatologia, Hospital Ramon y Cajal, Madrid, Spain;
  16. 16 University of Texas Medical Branch at Galveston, Galveston, Texas, Spain;
  17. 17 The University of Texas Health Science Center at San Antonio, San Antonio, Texas, Spain;
  18. 18 Servicio de Reumatologia, Hospital Xeral-Calde, Spain;
  19. 19 Servizio di Reumatologia ed Immunologia Clinica Spedali Civili, Spain;
  20. 20 Referral Center for Systemic Autoimmune Diseases, University of Milan, United States;
  21. 21 The University of Texas, United States
  1. Correspondence to: Blanca Rueda, CSIC, IPB Lopez-Neyra, PT Ciencias de la Salud, Avda. Conocimiento s/n, Armilla - Granada, 18100, Spain; blarume{at}


Objective: To investigate the possible association of the BANK1 gene with genetic susceptibility to systemic sclerosis (SSc) and its sub-phenotypes.

Methods: A large multicenter case-control association study including 2380 SSc patients and 3270 healthy controls from six independent case-control sets of Caucasian ancestry (American, Spanish, Dutch, German, Swedish and Italian) was conducted. Three putative functional BANK1 polymorphisms (rs17266594 T/C, rs10516487 G/A, rs3733197 G/A) were selected as genetic markers and genotyped by Taqman 5'allelic discrimination assay.

Results: A significant association of the rs10516487 G and rs17266594 T alleles with SSc susceptibility was observed (pooled OR 1.12 95 % CI 1.03-1.22; p=0.01 and pooled OR 1.14 95 % CI 1.05-1.25; p=0.003 respectively) whereas the rs3733197 genetic variant showed no statistically significant deviation. Stratification for cutaneous SSc phenotype revealed that the BANK1 rs10516487 G, rs17266594 T, and rs3733197 G alleles were strongly associated with susceptibility to diffuse SSc (dcSSc) (pooled OR 1.20 95 % CI 1.05-1.37 p=0.005, pooled OR 1.23 95 % CI 1.08-1.41 p=0.001 and pooled OR 1.15 95 % CI 1.02-1.31 p=0.02, respectively). Similarly, stratification for specific SSc auto-antibodies showed that the association of BANK1 rs10516487, rs17266594, and rs3733197 polymorphisms was restricted to the subgroup of patients carrying anti-topoisomerase I antibodies (pooled OR 1.20 95 % CI 1.02-1.41 p=0.03, pooled OR 1.24 95 % CI 1.05-1.46 p=0.01 and pooled OR 1.26 95 % CI 1.07-1.47 p=0.004 respectively).

Conclusion: Our results suggest that BANK1 gene confers susceptibility to SSc in general, and specifically to the dcSSc and anti-topoisomerase-I antibody subsets.

Statistics from

Review history and Supplementary material

  • Web Only Data ard.2009.118174

    Files in this Data Supplement:


    Request Permissions

    If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.

    Linked Articles

    • Miscellaneous
      BMJ Publishing Group Ltd and European League Against Rheumatism