Immunoglobulin allotype markers and HLA DR genes in type I diabetes mellitus.
Although it is now well established that insulin-dependent (type I) diabetes mellitus is closely associated with genes of the HLA-DR locus, the genetics of the disease remains an area of controversy. It is generally believed that the HLA-linked diabetes genes provide the majority of disease susceptibility to type I diabetes, however, there is some evidence for the existence of other non-HLA-linked genetic loci predisposing to this disorder. Therefore, allotypes of the Gm (immunoglobulin heavy chain) locus on chromosome 14 and of Km (immunoglobulin light chain) locus on chromosome 2 were studied in 180 caucasoid type I diabetic patients. No association between immunoglobulin allotype markers and the whole group of type I diabetes could be observed. However, a particular immunoglobulin allotype, G1m(a), and a particular Gm immunoglobulin phenotype (a-x-f+b+) showed a significant heterogeneity within the diabetics subdivided by HLA-DR type. The data of this study support the concept that (1) the genes in the HLA region provide the majority of, but not the only, genetic susceptibility to type I diabetes mellitus and (2) Gm-associated genes could interact with these susceptibility genes at least in the DR3+4 heterozygote type I diabetics. Further studies should be undertaken in order to elucidate a possible role of these factors in the humoral immune response of type I diabetics and their families.
D003922:Diabetes Mellitus, Type 1 / Q000235:genetics* / Q000276:immunology; D006680:HLA Antigens / Q000032:analysis; D006684:HLA-DR Antigens; D000949:Histocompatibility Antigens Class II / Q000032:analysis*; D006801:Humans; D007126:Immunoglobulin Allotypes / Q000032:analysis*; D007074:Immunoglobulin G; D007145:Immunoglobulin kappa-Chains; D010641:Phenotype
D006680:HLA Antigens; D006684:HLA-DR Antigens; D000949:Histocompatibility Antigens Class II; D007126:Immunoglobulin Allotypes; D007074:Immunoglobulin G; D007145:Immunoglobulin kappa-Chains