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.