TY - JOUR
T1 - BANK1 functional variants are associated with susceptibility to diffuse systemic sclerosis in Caucasians
AU - Rueda, Blanca
AU - Gourh, P.
AU - Broen, J.
AU - Agarwal, S. K.
AU - Simeon, C.
AU - Ortego-Centeno, N.
AU - Vonk, M. C.
AU - Coenen, M.
AU - Riemekasten, G.
AU - Hunzelmann, N.
AU - Hesselstrand, R.
AU - Tan, F. K.
AU - Reveille, J. D.
AU - Assassi, S.
AU - Garcia-Hernandez, F. J.
AU - Carreira, P.
AU - Camps, M.
AU - Fernandez-Nebro, A.
AU - Garcia De La Peña, P.
AU - Nearney, T.
AU - Hilda, D.
AU - Gónzalez-Gay, M. A.
AU - Airo, P.
AU - Beretta, L.
AU - Scorza, R.
AU - Radstake, T. R.D.J.
AU - Mayes, M. D.
AU - Arnett, F. C.
AU - Martin, J.
PY - 2010/1/1
Y1 - 2010/1/1
N2 - Objective: To investigate the possible association of the BANK1 gene with genetic susceptibility to systemic sclerosis (SSc) and its subphenotypes. Methods: A large multicentre case-control association study including 2380 patients with SSc 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 to 1.22; p=0.01 and pooled OR=1.14, 95% CI 1.05 to 1.25; p=0.003, respectively), whereas the rs3733197 genetic variant showed no statistically significant deviation. Stratification for cutaneous SSc phenotype showed 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 to 1.37, p=0.005; pooled OR=1.23, 95% CI 1.08 to 1.41, p=0.001; pooled OR=1.15, 95% CI 1.02 to 1.31, p=0.02, respectively). Similarly, stratification for specific SSc autoantibodies 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 to 1.41, p=0.03; pooled OR=1.24, 95% CI 1.05 to 1.46, p=0.01; pooled OR=1.26, 95% CI 1.07 to 1.47, p=0.004, respectively). Conclusion: The results suggest that the BANK1 gene confers susceptibility to SSc in general, and specifically to the dcSSc and anti-topoisomerase I antibody subsets.
AB - Objective: To investigate the possible association of the BANK1 gene with genetic susceptibility to systemic sclerosis (SSc) and its subphenotypes. Methods: A large multicentre case-control association study including 2380 patients with SSc 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 to 1.22; p=0.01 and pooled OR=1.14, 95% CI 1.05 to 1.25; p=0.003, respectively), whereas the rs3733197 genetic variant showed no statistically significant deviation. Stratification for cutaneous SSc phenotype showed 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 to 1.37, p=0.005; pooled OR=1.23, 95% CI 1.08 to 1.41, p=0.001; pooled OR=1.15, 95% CI 1.02 to 1.31, p=0.02, respectively). Similarly, stratification for specific SSc autoantibodies 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 to 1.41, p=0.03; pooled OR=1.24, 95% CI 1.05 to 1.46, p=0.01; pooled OR=1.26, 95% CI 1.07 to 1.47, p=0.004, respectively). Conclusion: The results suggest that the BANK1 gene confers susceptibility to SSc in general, and specifically to the dcSSc and anti-topoisomerase I antibody subsets.
UR - https://www.scopus.com/pages/publications/77950315193
U2 - 10.1136/ard.2009.118174
DO - 10.1136/ard.2009.118174
M3 - Article
C2 - 19815934
AN - SCOPUS:77950315193
SN - 0003-4967
VL - 69
SP - 700
EP - 705
JO - Annals of the Rheumatic Diseases
JF - Annals of the Rheumatic Diseases
IS - 4
ER -