Sporadic inclusion body myositis: HLA-DRB1 allele interactions influence disease risk and clinical phenotype |
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Authors: | Frank L. Mastaglia Merrilee Needham Adrian Scott Ian James Paul Zilko Timothy Day Lynette Kiers Alastair Corbett Campbell S. Witt Richard Allcock Nigel Laing Michael Garlepp Frank T. Christiansen |
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Affiliation: | 1. Department of Orthopaedics and Rehabilitation, Oregon Health and Science University, Portland, Oregon;2. Division of Infectious Diseases, Department of Medicine, Oregon Health and Science University, Portland, Oregon |
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Abstract: | Susceptibility to sIBM is strongly associated with the HLA-DRB1*03 allele and the 8.1 MHC ancestral haplotype (HLA-A1, B8, DRB1*03) but little is known about the effects of allelic interactions at the DRB1 locus or disease-modifying effects of HLA alleles. HLA-A, B and DRB1 genotyping was performed in 80 Australian sIBM cases and the frequencies of different alleles and allele combinations were compared with those in a group of 190 healthy controls. Genotype–phenotype correlations were also investigated. Amongst carriers of the HLA-DRB1*03 allele, DRB1*03/*01 heterozygotes were over-represented in the sIBM group (p < 0.003) while. DRB1*03/*04 heterozygotes were under-represented (p < 0.008). The mean age-at-onset (AAO) was 6.5 years earlier in DRB1*03/*01 heterozygotes who also had more severe quadriceps muscle weakness than the rest of the cohort. The findings indicate that interactions between the HLA-DRB1*03 allele and other alleles at the DRB1 locus can influence disease susceptibility and the clinical phenotype in sIBM. |
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Keywords: | Sporadic inclusion body myositis HLA alleles Phenotype |
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