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- W2013745916 abstract "In Caucasians, sIBM susceptibility is associated with the HLA-DRB1*0301 allele and the extended 8.1 MHC ancestral haplotype (HLA-A1, B8, DRB3*0101, DRB1*0301, DQB1*0201). Previous studies suggested that HLA-DRB1*0301 itself may not be the risk-conferring allele, but is in linkage disequilibrium with the susceptibility allele. In a recent recombinant mapping study Scott et al. (Neuromuscular Disorders 2011;235:77–83) refined the susceptibility region to a 172 kb segment including HLA-DRB3, HLA-DRA and BTNL2. In this study we analysed the carrier frequency of HLA-DRB3 and its alleles, DRB3*0101, DRB3*0202 and DRB3*0301, in 75 biopsy-confirmed sIBM patients of largely Anglo-Celtic origin who had previously undergone high-resolution HLA-DRB1 genotyping. HLA-DRB3 genotyping was performed using PCR–RFLP analysis. As the second expressed HLA-DRB locus, when present, can be either HLA-DRB3 or HLA-DRB4 or HLA-DRB5, carriage of HLA-DRB4 and HLA-DRB5 was also determined, by the presence or absence of amplified DRB4 or DRB5 specific amplicons. The percentage of sIBM individuals who carried a second DRB locus was higher than published figures from a normal Welsh population study (95.2% vs 74.2%, p < 0.001; Dorak et al., Genes & Immunity 2002; 3:263–9), as was the frequency of HLA-DRB3 homozygosity (65% vs 14%; p < 0.001). Fifty-one of the 75 sIBM patients carried the HLA-DRB3*0101 allele, compared with 54/75 who were HLA-DRB1*0301 carriers; 50/75 carried both DRB1*0301 and DRB3*0101. Thirty of the 51 DRB3*0101 carriers were homozygous, and the allelic frequency of DRB3*0101 was significantly higher than that of DRB1*0301 (52.7% vs 39%, p = 0.02). Our findings suggest that preferential carriage of HLA-DRB3 as the second expressed HLA-DRB locus, and homozygosity for HLA-DRB3*0101, which is in linkage dysequilibrium with HLA-DRB1*0301, are associated with increased susceptibility to sIBM." @default.
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- W2013745916 date "2012-10-01" @default.
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- W2013745916 title "G.P.61 Influence of HLA-DRB3 on susceptibility to sporadic inclusion body myositis" @default.
- W2013745916 doi "https://doi.org/10.1016/j.nmd.2012.06.167" @default.
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