title: Multiple loci in the HLA complex are associated with Addison's disease.
abstract: BACKGROUND
  A strong association between autoimmune Addison's disease (AAD) and major histocompatibility complex class II-encoded HLA-DRB1-DQA1-DQB1 haplotypes is well known. Recent evidence from other autoimmune diseases has suggested that class I-encoded HLA-A and HLA-B gene variants confer HLA-DRB1-DQA1-DQB1-independent effects on disease.
  
  
  OBJECTIVE
  We aimed to explore AAD predisposing effects of HLA-A and -B and further investigate the role of MICA and HLA-DRB1-DQA1-DQB1 in a much larger material than has previously been studied.
  
  
  METHODS
  HLA-A, -B, -DRB1, and -DQB1 and a microsatellite in MICA were genotyped in 414 AAD patients and 684 controls of Norwegian origin.
  
  
  RESULTS
  The strongest association was observed for the DRB1 locus, in which the DRB1*03:01 and DRB1*04:04 conferred increased risk of AAD, particularly in a heterozygous combination [odds ratio 22.13; 95% confidence interval (11.39-43.98); P = 6 × 10(-20)]. After conditioning on DRB1, association with AAD was still present for HLA-B and MICA, suggesting the presence of additional risk factors.
  
  
  CONCLUSIONS
  The major histocompatibility complex harbors multiple risk loci for AAD, in which DRB1 appears to represent the main risk factor.
authors.affiliation: Department of Medical Genetics, Oslo University Hospital, Ullevål, N-0407 Oslo, Norway. beate.skinningsrud@medisin.uio.no
authors.forename: Beate
authors.initials: B
authors.lastname: Skinningsrud
authors.forename: Benedicte A
authors.initials: BA
authors.lastname: Lie
authors.forename: Ewa
authors.initials: E
authors.lastname: Lavant
authors.forename: Joyce A
authors.initials: JA
authors.lastname: Carlson
authors.forename: Henry
authors.initials: H
authors.lastname: Erlich
authors.forename: Hanne E
authors.initials: HE
authors.lastname: Akselsen
authors.forename: Kristina
authors.initials: K
authors.lastname: Gervin
authors.forename: Anette B
authors.initials: AB
authors.lastname: Wolff
authors.forename: Martina M
authors.initials: MM
authors.lastname: Erichsen
authors.forename: Kristian
authors.initials: K
authors.lastname: Løvås
authors.forename: Eystein S
authors.initials: ES
authors.lastname: Husebye
authors.forename: Dag E
authors.initials: DE
authors.lastname: Undlien
mesh_terms: D000224:Addison Disease / Q000453:epidemiology / Q000235:genetics*; D000483:Alleles; D005805:Genes, MHC Class I / Q000235:genetics; D005802:Genes, MHC Class II / Q000235:genetics; D006680:HLA Antigens / Q000235:genetics*; D059811:HLA-DRB1 Chains / Q000235:genetics; D006239:Haplotypes; D006650:Histocompatibility Testing; D006801:Humans; D018895:Microsatellite Repeats; D009664:Norway / Q000453:epidemiology; D016017:Odds Ratio; D011110:Polymorphism, Genetic; D054340:Receptors, KIR / Q000502:physiology; D012044:Regression Analysis; D018570:Risk Assessment
chemical_list: D006680:HLA Antigens; D059811:HLA-DRB1 Chains; D054340:Receptors, KIR