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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}ipb.csic.es

Abstract

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.

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