A unified hypothesis for the complex genetics of HLA associations with IDDM.

摘要: Our understanding of the role HLA genes associated with insulin-dependentdiabetes mellitus (IDDM) is in disarray, despite recent improvements definition ofspecific alleles and haplotypes. Some are highly IDDM, other resistance to some susceptibility markedly influenced by trans -associated synergistic effects (DR3/4 heterozygotes) or protective (DR2/4 heterozygotes). This plethora genetic associations has spawned notion that there many contributing genes, which, turn, led search for shared structural features among different on IDDM-associated From a more mechanistic point view, however, wide range variable IDDM associations, both cis - -encoded and/or effects, suggests approach. article proposes hypothesis which can be simply explained single unifying concept: hierarchy affinities determines interaction between diabetogenic peptide class II molecules, an individual susceptible if molecule highest affinity such DQβ gene. The explicit formulation this proposal its implications provide explanation HLA-encoded dominant “protection” subtle observations related influences susceptibility.