Increase of HLA haplotype A9-Bw16 in familial insulin-dependent diabetes mellitus in northern-Finland.

Twenty-one families, each with two diabetic children, from North Finland were HLA typed. The grade of HLA identity between diabetic siblings was evaluated, and frequencies of various HLA antigens in familial cases were compared to those of non-familial cases from the same area. Ten pairs of diabetic children were HLA-identical and eleven haploidentical; two of the latter were identical for the HLA-D locus. These figures emphasize the significance of HLA-region associated genetic factors in the susceptibility to the disease, but do not support a simple dominant/recessive gene theory. There was a significant difference between familial and non-familial IDDM cases in the frequencies of B15, Bw16, B40 and Cw3 antigens. Bw16 was greatly increased and B15, B40 and Cw3 decreased among familial cases. The haplotype A9, Bw16 was common in familial cases, but, compared to healthy controls, the frequencies of the two antigens were also slightly increased among non-familial cases. Neither Dw3 nor Dw4 was associated with Bw16 antigen. The differences between familial and non-familial IDDM cases and the significance of the A9, Bw16 combination in the patients emphasize the heterogeneity of IDDM.