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




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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, pc7.4×10−5. DRB1*13:01 was found to be a protective allele for both early onset MG EOMG and LOMG OR 0.31, pc 4.71×10−4, a finding not previously described. No significant association was found to the DRB1*07:01 allele pnc = 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.



Autor: Angelina H. Maniaol , Ahmed Elsais, Åslaug R. Lorentzen, Jone F. Owe, Marte K. Viken, Hanne Sæther, Siri T. Flåm, Geir Bråthe

Fuente: http://plos.srce.hr/



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