Mapping of a candidate region for susceptibility to inclusion body myositis in the human major histocompatibility complex

Inclusion body myositis (IBM) is a form of idiopathic inflammatory myopathy of unknown aetiology, A strong association with HLA class II (HLA-DR3) sug gested a role for genes in the human major histo compatibility complex (MHC ) in the predisposition to this disease. In this study, we have taken advan tage of the ancestral haplotype (AH) concept and historical recombinations to map for a possible susceptibility gene(s) in the MHC. We performed detai led typing of three MHC-related HSP70 genes and defined allelic combination s in the context of MHC AH. We also modified existing methods to give a sim ple and accurate method for typing two TNF microsatellites. Using the HSP70 and TNF markers and HLA-DR, -B, and C4 typing of our patients with IBM, we defined a potential site for the MI-IC-associated susceptibility gene(s) i n the region between HLA-DR and C4.