Interaction of HLA and immunoglobulin antigens in type 1 (insulin-dependent) diabetes

We analyzed 88 unrelated subjects with Type 1 (insulin-dependent) diabetes and 64 sibling controls (maximum one per diabetic) for associations between immunoglobulin allotype antigens (GM and KM) and Type 1 diabetes. None were found. However, we did find interactions between GM, HLA-DR, and Type 1 diabetes (significant or of borderline significance after considering the effect of multiple tests): possession of Glm(2) appeared to increase susceptibility to diabetes in individuals who had HLA-DR3 but not HLA-DR4, while possession of G3m(5) appeared to increase susceptibility in individuals who had HLA-DR4 but not HLA-DR3. These results suggest that genetic predisposition to Type 1 diabetes is partially determined by alleles at the GM locus (or a locus in linkage disequilibrium with GM) interacting with alleles at the HLA-DR locus (or a locus in linkage disequilibrium with HLA-DR).