Genetic heterogeneity of diabetes and HLA.

Histocompatibility (HLA) antigens and genotypes B, D and DR were studied in large sample of Caucasian insulin dependent diabetic (IDD) probands. The associations between IDD and B8, B15, Dw3, Dw4, and DR3, and DR4 were measured by relative risks (RR) and delta values. Both the homozygotes (B8/8: RR 10, B 15/15: RR 7, DR3/3: RR32, DR4/4: RR34) and the heterozygotes (B8/15: RR 11, DR3/4: RR22) for the high-risk antigens showed highly significant elevation of the relative risks, yet there were no statistically significant differences between the homo- and the heterozygotes. The delta measurements supported the RR results. RR and delta were found significantly decreased for B7, Dw2, and DR2. There were no relationships observed between age at diagnosis or family history and HLA. Although we were unable to demonstrate a statistically significant difference between the RR for the high-risk antigens heterozygote vs. the high-risk antigen homozygotes, our study like many others shows that the RR is higher for the heterozygotes. Thus our data are compatible with genetic heterogeneity of IDD.