PMID- 22590574
OWN - NLM
STAT- MEDLINE
DCOM- 20120919
LR  - 20221207
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 7
IP  - 5
DP  - 2012
TI  - Late onset myasthenia gravis is associated with HLA DRB1*15:01 in the Norwegian 
      population.
PG  - e36603
LID - 10.1371/journal.pone.0036603 [doi]
LID - e36603
AB  - 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. 
      METHODOLOGY/PRINCIPAL FINDINGS: 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 x 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 x 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. CONCLUSION: 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.
FAU - Maniaol, Angelina H
AU  - Maniaol AH
AD  - Department of Neurology, Oslo University Hospital, Ulleval, Oslo, Norway. 
      angman@ous-hf.no
FAU - Elsais, Ahmed
AU  - Elsais A
FAU - Lorentzen, Aslaug R
AU  - Lorentzen AR
FAU - Owe, Jone F
AU  - Owe JF
FAU - Viken, Marte K
AU  - Viken MK
FAU - Saether, Hanne
AU  - Saether H
FAU - Flam, Siri T
AU  - Flam ST
FAU - Brathen, Geir
AU  - Brathen G
FAU - Kampman, Margitta T
AU  - Kampman MT
FAU - Midgard, Rune
AU  - Midgard R
FAU - Christensen, Marte
AU  - Christensen M
FAU - Rognerud, Anna
AU  - Rognerud A
FAU - Kerty, Emilia
AU  - Kerty E
FAU - Gilhus, Nils Erik
AU  - Gilhus NE
FAU - Tallaksen, Chantal M E
AU  - Tallaksen CM
FAU - Lie, Benedicte A
AU  - Lie BA
FAU - Harbo, Hanne F
AU  - Harbo HF
LA  - eng
PT  - Clinical Trial
PT  - Journal Article
PT  - Multicenter Study
PT  - Research Support, Non-U.S. Gov't
DEP - 20120509
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (HLA-DRB1 Chains)
RN  - 0 (HLA-DRB1*15:01 antigen)
SB  - IM
MH  - Adult
MH  - Age of Onset
MH  - *Alleles
MH  - Cohort Studies
MH  - Female
MH  - HLA-DRB1 Chains/*genetics/immunology
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - Myasthenia Gravis/epidemiology/*genetics/immunology
MH  - Norway
MH  - Risk Factors
MH  - White People
PMC - PMC3348874
COIS- Competing Interests: The authors have declared that no competing interests exist.
EDAT- 2012/05/17 06:00
MHDA- 2012/09/20 06:00
PMCR- 2012/05/09
CRDT- 2012/05/17 06:00
PHST- 2012/01/27 00:00 [received]
PHST- 2012/04/03 00:00 [accepted]
PHST- 2012/05/17 06:00 [entrez]
PHST- 2012/05/17 06:00 [pubmed]
PHST- 2012/09/20 06:00 [medline]
PHST- 2012/05/09 00:00 [pmc-release]
AID - PONE-D-12-02962 [pii]
AID - 10.1371/journal.pone.0036603 [doi]
PST - ppublish
SO  - PLoS One. 2012;7(5):e36603. doi: 10.1371/journal.pone.0036603. Epub 2012 May 9.