Only one DQ-beta restriction fragment pattern of each DR specificity is associated with insulin-dependent diabetes.
Insulin-dependent diabetes is generally associated with the serologic HLA-DR specificities 3 and 4, in particular with DR-3,4 heterozygosity. The disease is negatively associated with DR-2. To investigate these associations further at the genomic level, DNA from 13 families with a proband having insulin-dependent diabetes, from 11 other individuals with the same disease, and from HLA-DR-matched control individuals was subjected to restriction fragment analysis. Three different enzymes (Bam HI, Eco RI, and Pvu II) and cDNA clones for three HLA-D region class II antigen alpha- and beta-chains (DR-beta, DQ-beta, and DQ-alpha) were used. In six families, a total of 11 siblings HLA-DR-identical to the proband were examined. There was no discrepancy between the hybridization patterns of the proband and those of the DR-identical siblings. Two different DQ-B fragment patterns were detected with each one of the serologic specificities DR-2 and DR-4. In both cases, only one of the patterns correlated significantly with diabetes. Thus, DQ-beta genomic hybridization may be used in conjunction with HLA-DR typing to identify individuals with higher relative risk to acquire insulin-dependent diabetes. These results may suggest that insulin-dependent diabetes is associated with the DQ rather than with the DR locus.
D000293:Adolescent; D000328:Adult; D000368:Aged; D000483:Alleles; D004247:DNA / Q000235:genetics; D004262:DNA Restriction Enzymes; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics* / Q000276:immunology; D000939:Epitopes / Q000235:genetics*; D006683:HLA-DQ Antigens; D006684:HLA-DR Antigens; D000949:Histocompatibility Antigens Class II / Q000235:genetics*; D006650:Histocompatibility Testing; D006801:Humans; D008875:Middle Aged; D011110:Polymorphism, Genetic
D000939:Epitopes; D006683:HLA-DQ Antigens; D006684:HLA-DR Antigens; C040626:HLA-Dx antigen; D000949:Histocompatibility Antigens Class II; D004247:DNA; D004262:DNA Restriction Enzymes