title: BANK1 functional variants are associated with susceptibility to diffuse systemic sclerosis in Caucasians.
abstract: 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).
  
  
  CONCLUSIONS
  The results suggest that the BANK1 gene confers susceptibility to SSc in general, and specifically to the dcSSc and anti-topoisomerase I antibody subsets.
authors.affiliation: Referral Center for Systemic Autoimmune Diseases, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, University of Milan. [corrected]
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authors.lastname: Ortego-Centeno
authors.forename: M C
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authors.lastname: Hunzelmann
authors.forename: R
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authors.lastname: Hesselstrand
authors.forename: F K
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authors.lastname: Tan
authors.forename: J D
authors.initials: JD
authors.lastname: Reveille
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authors.lastname: Assassi
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authors.initials: FJ
authors.lastname: Garcia-Hernandez
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authors.lastname: Carreira
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authors.lastname: Garcia de la Peña
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authors.forename: D
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authors.lastname: Hilda
authors.forename: M A
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authors.lastname: Gónzalez-Gay
authors.forename: P
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authors.lastname: Airo
authors.forename: L
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authors.lastname: Beretta
authors.forename: R
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authors.forename: T R D J
authors.initials: TR
authors.lastname: Radstake
authors.forename: M D
authors.initials: MD
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mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics*; D001323:Autoantibodies / Q000032:analysis; D016022:Case-Control Studies; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D045743:Scleroderma, Diffuse / Q000235:genetics* / Q000276:immunology; D044465:White People / Q000235:genetics*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D001323:Autoantibodies; C447641:BANK1 protein, human; D008565:Membrane Proteins