Résumé :
|
Communication n° 23 INTRODUCTION : Sporadic inclusion body myositis (sIBM) is a chronic inflammatory disease. We have previously identified two MHC haplotypes, HLA-A1,B8,DR3 and HLA-B35,DR1, that are associated with susceptibility to sIBM in Caucasians [1]. We showed that the HLA-DR locus is unlikely to be directly causative and that the effect maps telomeric of DR3 in the Central HLA region. sIBM is much rarer in ethnic groups other than Caucasians. OBJECTIVES : Although sIBM is rare in non-Caucasians, we wished to test whether the disease is also associated with particular HLA haplotypes in other ethnic groups. METHODS DNA samples were extracted from muscle biopsies of 31 sIBM patients drawn from all over Japan. We performed high resolution sequence-based HLA-B and HLA-DRB1 typing on all samples. RESULTS : HLA-B*5201 was found in 67% (21/31) of patients and HLA-DRB1*1502 was found in 71% (22/31) of patients. Both alleles are found together as part of a conserved haplotype that is found in approximately 10% of the healthy Japanese population. We also identified 4 and 3 individuals homozygous for HLA-B*5201 and HLA-DRB1*1502, respectively. We calculated a statistically significant odds ratio of approximately 5.6. CONCLUSIONS : We have now identified three separate HLA haplotypes associated with sIBM in two different ethnic groups. The next question is whether the three haplotypes lead to sIBM susceptibility by the same mechanism. Future studies will concentrate on high density SNP genotyping in the HLA region that we have identified in the Caucasian population. REFERENCE : 1. Price, P., et al., Two major histocompatibility complex haplotypes influence susceptibility to sporadic inclusion body myositis: critical evaluation of an association with HLA-DR3. Tissue Antigens, 2004. 64(5): p. 575-80.
|