title: Influence of HLA-DRB1 alleles on the susceptibility and resistance to multiple sclerosis in Japanese patients with respect to anti-aquaporin 4 antibody status.
abstract: BACKGROUND
  Epistatic interactions between human leukocyte antigen (HLA)-DRB1 alleles alter multiple sclerosis (MS) risk in Caucasians. Such interactions have never been studied in Asian MS patients.
  
  
  OBJECTIVE
  To investigate the influence of HLA-DRB1 alleles, including epistatic interactions at this locus, in Japanese MS patients with and without the anti-aquaporin 4 (AQP4) antibody.
  
  
  METHODS
  The HLA-DRB1 locus was genotyped in 108 MS patients and 127 healthy controls. MS patients were further classified into two groups according to anti-AQP4 antibody status (27 positive and 81 negative).
  
  
  RESULTS
  HLA-DRB1*09 (adjusted odds ratio (OR) = 0.243, 95% confidence interval (CI) 0.099-0.533) and HLA-DRB1*01 (adjusted OR = 0.327, 95% CI 0.103-0.873) decreased the incidence of anti-AQP4 antibody-negative MS. By contrast, HLA-DRB1*12 increased the risk of anti-AQP4 antibody-positive MS (adjusted OR = 3.691, 95% CI 1.233-10.565). Individuals with HLA-DRB1*09/15 decreased the risk of anti-AQP4 antibody-negative MS (adjusted OR = 0.164, 95% CI 0.026-0.593), while those with HLA-DRB1*12/15 increased the risk of anti-AQP4 antibody-positive MS (adjusted OR = 10.870, 95% CI 2.004-81.752).
  
  
  CONCLUSIONS
  The ability of HLA-DRB1*09 to reduce the risk of anti-AQP4 antibody-negative MS may arise from an interaction with HLA-DRB1*15. By contrast, HLA-DRB1*12 increases susceptibility to anti-AQP4 antibody-positive MS, possibly via an interaction with HLA-DRB1*15.
authors.affiliation: Department of Neurology, Neurological Institute, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
authors.forename: N
authors.initials: N
authors.lastname: Isobe
authors.forename: T
authors.initials: T
authors.lastname: Matsushita
authors.forename: R
authors.initials: R
authors.lastname: Yamasaki
authors.forename: S V
authors.initials: SV
authors.lastname: Ramagopalan
authors.forename: Y
authors.initials: Y
authors.lastname: Kawano
authors.forename: Y
authors.initials: Y
authors.lastname: Nishimura
authors.forename: G C
authors.initials: GC
authors.lastname: Ebers
authors.forename: J
authors.initials: J
authors.lastname: Kira
mesh_terms: D051401:Aquaporin 4 / Q000276:immunology*; D044466:Asian People / Q000235:genetics; D001323:Autoantibodies / Q000097:blood*; D016022:Case-Control Studies; D004843:Epistasis, Genetic; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006684:HLA-DR Antigens / Q000235:genetics*; D059811:HLA-DRB1 Chains; D006801:Humans; D007564:Japan; D016015:Logistic Models; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000208:ethnology / Q000235:genetics* / Q000276:immunology / Q000517:prevention & control; D016017:Odds Ratio; D010641:Phenotype; D018570:Risk Assessment; D012307:Risk Factors
chemical_list: C496030:AQP4 protein, human; D051401:Aquaporin 4; D001323:Autoantibodies; D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains