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Clinical Trial
, 7 (5), e36603

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

Clinical Trial

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

Angelina H Maniaol et al. PLoS One.


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 × 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.

Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.


Figure 1
Figure 1. Schematic overview of associated HLA alleles in MG.
The HLA complex on chromosome 6 with its division into three classes. Some key genes and their order on the chromosome are given. Associated HLA alleles reported earlier in Caucasian MG patients (see text for complete references) are illustrated together with the results from the present study.

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