Class II histocompatibility genes and insulin-dependent diabetes mellitus

Models for IDDM susceptibility based on single amino acid substitutions in class II histocompatibility genes are attractive in simplicity but are largely inconsistent with genetic epidemiological data. A simple correlation between IDDM and residue 57 of the DQ beta chain does not hold in Oriental IDDM patients, cannot account for DR3,DR4 synergism and does not explain different modes of inheritance of DR3- and DR4-related IDDM determinants. Residue 70/DR beta correlates equally well, if not better, with IDDM than does residue 57/DQ beta, but IDDM genotype distributions are compatible with multi-locus involvement of DR beta and DQ beta genes.