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) suggested a role for genes in the human major histocompatibility complex (MHC) in the predisposition to this disease. In this study, we have taken advantage of the ancestral haplotype (AH) concept and historical recombinations to map for a possible susceptibility gene(s) in the MHC. We performed detailed typing of three MHC-related HSP70 genes and defined allelic combinations in the context of MHC AH. We also modified existing methods to give a simple 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 MHC-associated susceptibility gene(s) in the region between HLA-DR and C4.
Kok
C C
CC
Australian Neuromuscular Research Institute, Queen Elizabeth II Medical Centre, Nedlands, Western Australia.
Croager
E J
EJ
Witt
C S
CS
Kiers
L
L
Mastaglia
F L
FL
Abraham
L J
LJ
Garlepp
M J
MJ
D000483:Alleles; D002874:Chromosome Mapping; D005260:Female; D020022:Genetic Predisposition to Disease; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics; D006801:Humans; D008285:Major Histocompatibility Complex; D008297:Male; D018895:Microsatellite Repeats; D018979:Myositis, Inclusion Body / Q000235:genetics* / Q000276:immunology; D010375:Pedigree; D011110:Polymorphism, Genetic; D012150:Polymorphism, Restriction Fragment Length; D018807:Polymorphism, Single-Stranded Conformational; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics
D018840:HSP70 Heat-Shock Proteins; D014409:Tumor Necrosis Factor-alpha