title: Epistatic interaction between BANK1 and BLK in rheumatoid arthritis: results from a large trans-ethnic meta-analysis.
abstract: BACKGROUND
  BANK1 and BLK belong to the pleiotropic autoimmune genes; recently, epistasis between BANK1 and BLK was detected in systemic lupus erythematosus. Although BLK has been reproducibly identified as a risk factor in rheumatoid arthritis (RA), reports are conflicting about the contribution of BANK1 to RA susceptibility. To ascertain the real impact of BANK1 on RA genetic susceptibility, we performed a large meta-analysis including our original data and tested for an epistatic interaction between BANK1 and BLK in RA susceptibility.
  
  
  METHODS
  We investigated data for 1,915 RA patients and 1,915 ethnically matched healthy controls genotyped for BANK1 rs10516487 and rs3733197 and BLK rs13277113. The association of each SNP and RA was tested by logistic regression. Multivariate analysis was then used with an interaction term to test for an epistatic interaction between the SNPs in the 2 genes.
  
  
  RESULTS
  None of the SNPs tested individually was significantly associated with RA in the genotyped samples. However, we detected an epistatic interaction between BANK1 rs3733197 and BLK rs13277113 (P(interaction)  = 0.037). In individuals carrying the BLK rs13277113 GG genotype, presence of the BANK1 rs3733197 G allele increased the risk of RA (odds ratio 1.21 [95% confidence interval 1.04-1.41], P = 0.015. Combining our results with those of all other studies in a large trans-ethnic meta-analysis revealed an association of the BANK1 rs3733197 G allele and RA (1.11 [1.02-1.21], P = 0.012).
  
  
  CONCLUSIONS
  This study confirms BANK1 as an RA susceptibility gene and for the first time provides evidence for epistasis between BANK1 and BLK in RA. Our results illustrate the concept of pleiotropic epistatic interaction, suggesting that BANK1 and BLK might play a role in RA pathogenesis.
authors: Institut National de la Santé et de la Recherche Médicale UMR-S946, Univ Paris Diderot, Paris, France.
authors: Emmanuelle
authors: E
authors: Génin
authors: Baptiste
authors: B
authors: Coustet
authors: Yannick
authors: Y
authors: Allanore
authors: Ikue
authors: I
authors: Ito
authors: Maria
authors: M
authors: Teruel
authors: Arnaud
authors: A
authors: Constantin
authors: Thierry
authors: T
authors: Schaeverbeke
authors: Adeline
authors: A
authors: Ruyssen-Witrand
authors: Shigeto
authors: S
authors: Tohma
authors: Alain
authors: A
authors: Cantagrel
authors: Olivier
authors: O
authors: Vittecoq
authors: Thomas
authors: T
authors: Barnetche
authors: Xavier
authors: X
authors: Le Loët
authors: Patrice
authors: P
authors: Fardellone
authors: Hiroshi
authors: H
authors: Furukawa
authors: Olivier
authors: O
authors: Meyer
authors: Benjamin
authors: B
authors: Fernández-Gutiérrez
authors: Alejandro
authors: A
authors: Balsa
authors: Miguel A
authors: MA
authors: González-Gay
authors: Gilles
authors: G
authors: Chiocchia
authors: Naoyuki
authors: N
authors: Tsuchiya
authors: Javier
authors: J
authors: Martin
authors: Philippe
authors: P
authors: Dieudé
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics*; D000328:Adult; D000483:Alleles; D001172:Arthritis, Rheumatoid / Q000208:ethnology / Q000235:genetics*; D044466:Asian People / Q000235:genetics; D016022:Case-Control Studies; D004843:Epistasis, Genetic; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D008875:Middle Aged; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide; D044465:White People / Q000235:genetics; D019061:src-Family Kinases / Q000235:genetics*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C447641:BANK1 protein, human; D008565:Membrane Proteins; C584409:BLK protein, human; D019061:src-Family Kinases
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