title: Late onset myasthenia gravis is associated with HLA DRB1*15:01 in the Norwegian population.
abstract: BACKGROUND
  Acquired myasthenia gravis (MG) is a rare antibody-mediated autoimmune disease caused by impaired neuromuscular transmission, leading to abnormal muscle fatigability. The aetiology is complex, including genetic risk factors of the human leukocyte antigen (HLA) complex and unknown environmental factors. Although associations between the HLA complex and MG are well established, not all involved components of the HLA predisposition to this heterogeneous disease have been revealed. Well-powered and comprehensive HLA analyses of subgroups in MG are warranted, especially in late onset MG.
  
  
  RESULTS
  This case-control association study is of a large population-based Norwegian cohort of 369 MG patients and 651 healthy controls. We performed comprehensive genotyping of four classical HLA loci (HLA-A, -B, -C and -DRB1) and showed that the DRB1*15:01 allele conferred the strongest risk in late onset MG (LOMG; onset ≥ 60 years) (OR 2.38, p(c)7.4 × 10(-5)). DRB1*13:01 was found to be a protective allele for both early onset MG (EOMG) and LOMG (OR 0.31, p(c) 4.71 × 10(-4)), a finding not previously described. No significant association was found to the DRB1*07:01 allele (p(nc) = 0.18) in a subset of nonthymomatous anti-titin antibody positive LOMG as reported by others. HLA-B*08 was mapped to give the strongest contribution to EOMG, supporting previous studies.
  
  
  CONCLUSIONS
  The results from this study provide important new information concerning the susceptibility of HLA alleles in Caucasian MG, with highlights on DRB1*15:01 as being a major risk allele in LOMG.
authors.affiliation: Department of Neurology, Oslo University Hospital, Ullevål, Oslo, Norway. angman@ous-hf.no
authors.forename: Angelina H
authors.initials: AH
authors.lastname: Maniaol
authors.forename: Ahmed
authors.initials: A
authors.lastname: Elsais
authors.forename: Åslaug R
authors.initials: ÅR
authors.lastname: Lorentzen
authors.forename: Jone F
authors.initials: JF
authors.lastname: Owe
authors.forename: Marte K
authors.initials: MK
authors.lastname: Viken
authors.forename: Hanne
authors.initials: H
authors.lastname: Sæther
authors.forename: Siri T
authors.initials: ST
authors.lastname: Flåm
authors.forename: Geir
authors.initials: G
authors.lastname: Bråthen
authors.forename: Margitta T
authors.initials: MT
authors.lastname: Kampman
authors.forename: Rune
authors.initials: R
authors.lastname: Midgard
authors.forename: Marte
authors.initials: M
authors.lastname: Christensen
authors.forename: Anna
authors.initials: A
authors.lastname: Rognerud
authors.forename: Emilia
authors.initials: E
authors.lastname: Kerty
authors.forename: Nils Erik
authors.initials: NE
authors.lastname: Gilhus
authors.forename: Chantal M E
authors.initials: CM
authors.lastname: Tallaksen
authors.forename: Benedicte A
authors.initials: BA
authors.lastname: Lie
authors.forename: Hanne F
authors.initials: HF
authors.lastname: Harbo
mesh_terms: D000328:Adult; D017668:Age of Onset; D000483:Alleles; D015331:Cohort Studies; D005260:Female; D059811:HLA-DRB1 Chains / Q000235:genetics* / Q000276:immunology; D006801:Humans; D008297:Male; D008875:Middle Aged; D009157:Myasthenia Gravis / Q000453:epidemiology / Q000235:genetics* / Q000276:immunology; D009664:Norway; D012307:Risk Factors; D044465:White People
chemical_list: D059811:HLA-DRB1 Chains; C489631:HLA-DRB1*15:01 antigen