BF types and the mode of inheritance of insulin-dependent diabetes mellitus (IDDM)

Insulin-dependent diabetes mellitus (IDDM) has been found to be highly associated with a rare allele of the complement protein, properdin factor B (BF). Assuming that there is a susceptibility gene for IDDM tightly linked to the genetic locus for BF and the major histocompatibility complex (MHC), the distribution of BF types in more than 1100 North American IDDM patients strongly argues for the rejection of dominant, epistatic, and overdominant modes of inheritance. Other evidence suggesting complex modes of inheritance for IDDM is reviewed and it is concluded that our observations and published data are consistent with the idea of susceptibility to IDDM being inherited as a simple autosomal recessive trait. C4 and C2 types, also linked to BF and the MHC, were investigated too. C4 Fs0 was found to be increased in association with BF F1, while C4 f0S and C2 b were each found to occur twice as frequently as in a control population and will be of value in defining haplotypes associated with susceptibility to IDDM.