The genetic susceptibility to IDDM in British and south Indian subjects

Associations of insulin dependent diabetes mellitus exist with the HLA-DR antigens DR3 and DR4 in both British Caucasoid and Dravidian subjects. However, it is only in British Caucasoids that an increased relative risk is found in those subjects who co-inherit both of these antigens. The nature of these HLA associations has been explored using Southern blot techniques and radioactive HLA-D region probes. In both populations the same DR4 related polymorphism was found in IDDM subjects whereas different HLA-DR3 preferential allelic associations were observed between British Caucasoid and Dravidian subjects. The best differentiation between diabetics and controls was found by a combination of HLA-DQ region alpha and beta polymorphisms which were totally different for the two populations. These data indicate that at least one gene involved in the susceptibility to IDDM is located within the HLA-DQ region and this may be related to HLA-DR4. The location of a DR3 related gene remains elusive and may be the DR beta gene encoding DR3 itself. In both populations it is a combination of two HLA-D region haplotypes which is strongly associated with IDDM leading to the possibility of trans complementation leading to the formation of mixed isotypic dimers.