Interaction between HLA antigens and immunoglobulin (Gm) allotypes in susceptibility to type I diabetes.
HLA-A,B,C and DR typing was performed on 108 Caucasian type I diabetic patients, 68 being Gm typed. The expected association with B8, B18, Bw62, DR3 and DR4 was observed as well as an excess of DR3/4 heterozygotes. DR2 was decreased in frequency. In the total patient group, no Gm association was observed but when the patients were subgrouped according to HLA type, HLA/Gm interactive effects were seen. An increase in Gm(1,3;5) was observed in DR3 positive, DR4 negative patients. This association occurred predominantly in females (compared with DR4 and DR3/4 patients of the same Gm phenotype who were predominantly male). Further genetic heterogeneity was identified within DR3/4 patients. Within this group, Bw62 was increased (strongly suggestive of Bw62-DR4 haplotypes) within B8, Gm heterozygotes compared with B8, Gm homozygotes. This finding can be interpreted as indicating a three-way interaction between genes on two HLA haplotypes and Gm-linked genes. These results reflect the genetic heterogeneity and complexity of insulin-dependent diabetes mellitus and explain in part the previous failure of simple genetic models to adequately explain inheritance patterns observed.
D003922:Diabetes Mellitus, Type 1 / Q000276:immunology*; D004198:Disease Susceptibility; D005260:Female; D006680:HLA Antigens / Q000032:analysis*; D006801:Humans; D007126:Immunoglobulin Allotypes / Q000032:analysis*; D008297:Male; D010641:Phenotype; D012727:Sex Characteristics
D006680:HLA Antigens; D007126:Immunoglobulin Allotypes