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Late Onset Myasthenia Gravis Is Associated with HLA DRB1*15:01 in the Norwegian Population

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 environ...

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Autores principales: Maniaol, Angelina H., Elsais, Ahmed, Lorentzen, Åslaug R., Owe, Jone F., Viken, Marte K., Sæther, Hanne, Flåm, Siri T., Bråthen, Geir, Kampman, Margitta T., Midgard, Rune, Christensen, Marte, Rognerud, Anna, Kerty, Emilia, Gilhus, Nils Erik, Tallaksen, Chantal M. E., Lie, Benedicte A., Harbo, Hanne F.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3348874/
https://www.ncbi.nlm.nih.gov/pubmed/22590574
http://dx.doi.org/10.1371/journal.pone.0036603
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author Maniaol, Angelina H.
Elsais, Ahmed
Lorentzen, Åslaug R.
Owe, Jone F.
Viken, Marte K.
Sæther, Hanne
Flåm, Siri T.
Bråthen, Geir
Kampman, Margitta T.
Midgard, Rune
Christensen, Marte
Rognerud, Anna
Kerty, Emilia
Gilhus, Nils Erik
Tallaksen, Chantal M. E.
Lie, Benedicte A.
Harbo, Hanne F.
author_facet Maniaol, Angelina H.
Elsais, Ahmed
Lorentzen, Åslaug R.
Owe, Jone F.
Viken, Marte K.
Sæther, Hanne
Flåm, Siri T.
Bråthen, Geir
Kampman, Margitta T.
Midgard, Rune
Christensen, Marte
Rognerud, Anna
Kerty, Emilia
Gilhus, Nils Erik
Tallaksen, Chantal M. E.
Lie, Benedicte A.
Harbo, Hanne F.
author_sort Maniaol, Angelina H.
collection PubMed
description 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 ≥60years) (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. 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.
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spelling pubmed-33488742012-05-15 Late Onset Myasthenia Gravis Is Associated with HLA DRB1*15:01 in the Norwegian Population Maniaol, Angelina H. Elsais, Ahmed Lorentzen, Åslaug R. Owe, Jone F. Viken, Marte K. Sæther, Hanne Flåm, Siri T. Bråthen, Geir Kampman, Margitta T. Midgard, Rune Christensen, Marte Rognerud, Anna Kerty, Emilia Gilhus, Nils Erik Tallaksen, Chantal M. E. Lie, Benedicte A. Harbo, Hanne F. PLoS One Research Article 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 ≥60years) (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. 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. Public Library of Science 2012-05-09 /pmc/articles/PMC3348874/ /pubmed/22590574 http://dx.doi.org/10.1371/journal.pone.0036603 Text en Maniaol et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Maniaol, Angelina H.
Elsais, Ahmed
Lorentzen, Åslaug R.
Owe, Jone F.
Viken, Marte K.
Sæther, Hanne
Flåm, Siri T.
Bråthen, Geir
Kampman, Margitta T.
Midgard, Rune
Christensen, Marte
Rognerud, Anna
Kerty, Emilia
Gilhus, Nils Erik
Tallaksen, Chantal M. E.
Lie, Benedicte A.
Harbo, Hanne F.
Late Onset Myasthenia Gravis Is Associated with HLA DRB1*15:01 in the Norwegian Population
title Late Onset Myasthenia Gravis Is Associated with HLA DRB1*15:01 in the Norwegian Population
title_full Late Onset Myasthenia Gravis Is Associated with HLA DRB1*15:01 in the Norwegian Population
title_fullStr Late Onset Myasthenia Gravis Is Associated with HLA DRB1*15:01 in the Norwegian Population
title_full_unstemmed Late Onset Myasthenia Gravis Is Associated with HLA DRB1*15:01 in the Norwegian Population
title_short Late Onset Myasthenia Gravis Is Associated with HLA DRB1*15:01 in the Norwegian Population
title_sort late onset myasthenia gravis is associated with hla drb1*15:01 in the norwegian population
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3348874/
https://www.ncbi.nlm.nih.gov/pubmed/22590574
http://dx.doi.org/10.1371/journal.pone.0036603
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