Sporadic inclusion body myositis: HLA-DRB1 allele interactions influence disease risk and clinical phenotype

Neuromuscul Disord. 2009 Nov;19(11):763-5. doi: 10.1016/j.nmd.2009.07.015. Epub 2009 Aug 31.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Age of Onset
  • Cohort Studies
  • Female
  • Genetic Association Studies / methods
  • Genetic Predisposition to Disease*
  • Genotype
  • HLA-DR Antigens / genetics*
  • HLA-DR3 Antigen / genetics
  • HLA-DRB1 Chains
  • Humans
  • Kaplan-Meier Estimate
  • Logistic Models
  • Male
  • Middle Aged
  • Myositis, Inclusion Body / genetics*
  • Myositis, Inclusion Body / mortality
  • Phenotype*
  • Severity of Illness Index

Substances

  • HLA-DR Antigens
  • HLA-DR3 Antigen
  • HLA-DRB1 Chains