HETEROZYGOUS EXPRESSION OF INSULIN-DEPENDENT DIABETES-MELLITUS (IDDM) DETERMINANTS IN THE HLA SYSTEM

  • 1 January 1983
    • journal article
    • research article
    • Vol. 35  (2) , 201-213
Abstract
HLA phenotypes of cases with insulin-dependent diabetes mellitus (IDDM) and identity by descent of HLA haplotypes in affected sib-pairs support an intermediate model in which morbid risk is increased by one HLA-linked IDDM determinant, and greatly increased by 2 determinants, which may be qualitatively different in DR3 and DR4 haplotypes. Linkage analysis allowing for gametic disequilibrium reveals no recombination in pedigrees with a DR3/DR4 propositus, but spurious recombination in the remaining pedigrees. This evidence favors interaction of unlinked IDDM determinants to produce affection in a small proportion of heterozygotes for an HLA-linked determinant. Partition of data by HLA type of the propositus (ideally by DR and the complement types jointly) is a powerful method to resolve etiological heterogeneity for HLA-associated diseases.