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G.P.16.09 Epistatic interactions between DRB1 alleles influence susceptibility and clinical phenotype in sporadic inclusion body myositis (sIBM)
Journal article   Peer reviewed

G.P.16.09 Epistatic interactions between DRB1 alleles influence susceptibility and clinical phenotype in sporadic inclusion body myositis (sIBM)

F.L. Mastaglia, M. Needham, A. Scott, I. James, T. Day, L. Kiers, A. Corbett, C. Witt, M. Garlepp, R. Allcock, …
Neuromuscular Disorders, Vol.19(8-9)
2009
DOI: https://doi.org/10.1016/j.nmd.2009.06.340
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Abstract

Background: Susceptibility to sIBM is strongly associated with HLA-DRB1*03 and the 8.1 MHC ancestral haplotype but little is known about the effect of allelic interactions at the DRB1 locus or disease-modifying effects of HLA alleles. Objectives: To determine whether DRB1 allele interactions influence susceptibility to sIBM and disease phenotype. Patients & Methods: HLA-DRB1 genotyping was carried out in 80 biopsy-proven cases of sIBM using high-resolution DNA sequencing in 55 cases and serological typing in 25 cases. Allele frequencies were compared with those in a group of 190 healthy population controls. All patients had manual muscle testing using an expanded 10-point MRC scale as well as documentation of historical aspects of their disease. Results: The strong positive association with HLA-DRB1*03 was confirmed (OR 9.6) while negative associations were found with HLA-DRB1∗04 and DRB1∗07. In addition, amongst those carrying the HLA-DRB1∗03 allele DRB1∗03/∗01 heterozygotes were over-represented in the sIBM group (p < 0.003). DRB1∗03/∗04 was the most significantly under-represented combination (p < 0.008) and remained so when those with DRB1∗03/∗01 were excluded (p = 0.03). Age at onset (AAO) was not associated with any individual allele but the mean AAO was earlier in the HLA-DRB1∗03/∗01 heterozygotes (55.8 years vs 62.3 years, p = 0.006) who also had more severe quadriceps weakness than the rest of the cohort (average MRC grade 3.57 vs 5.63, p = 0.003). Conclusions: The findings indicate that the HLA-DRB1*03 allele interacts with other alleles at the DRB1 locus to influence susceptibility to sIBM as well as AAO of the disease and disease severity.

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