Late onset myasthenia gravis is associated with HLA DRB115:01 in the Norwegian population

• Published in: PloS one Vol. 7; no. 5; p. e36603
• Main Authors: 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
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 09.05.2012; Public Library of Science (PLoS)
• Subjects: Adult; African Americans; Age; Age of Onset; Alleles; Analysis; Antibodies; Antigens; Clinical medical disciplines: 750; Clinical medicine; Cohort Studies; Connectin; Drb1 protein; Environmental factors; European Continental Ancestry Group; Female; Genotyping; Haplotypes; Histocompatibility antigen HLA; HLA antigens; HLA-DRB1 Chains - genetics; HLA-DRB1 Chains - immunology; Hospitals; Humans; Immunoglobulins; Immunology; Klinisk medisinske fag: 750; Leukocytes; Ligands; Male; Medical disciplines: 700; Medical research; Medicine; Medisinske Fag: 700; Middle Aged; Multiple sclerosis; Muscles; Myasthenia; Myasthenia gravis; Myasthenia Gravis - epidemiology; Myasthenia Gravis - genetics; Myasthenia Gravis - immunology; Neurology; Neuromuscular junctions; Neuromuscular transmission; Neurophysiology; Norway; Risk analysis; Risk Factors; Studies; Subgroups; Task forces; Tropemedisin: 761; Tropical medicine: 761; VDP; Norway
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0036603

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. 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. 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.