Genetic linkage between the antigenic group (Ag) variation and the apolipoprotein B gene: assignment of the Ag locus.

The antigenic group (Ag) system of homospecific human serum antigens of low density lipoprotein is detected by antiserum from multiply transfused patients. A complex series of common Ag alleles has been described, but the biochemical nature of this polymorphism is uncertain. Here we report that DNA polymorphisms at the human apolipoprotein B (apoB) locus are very closely linked to alleles of the Ag system. We also show a strong association between Ag(x) and a polymorphism detected with the restriction endonuclease Xba I. We conclude that the immunologically determined Ag system represents protein polymorphism of apoB rather than primary genetic differences in posttranslational processing or lipid binding. These studies therefore demonstrate that the Ag locus is located on the short arm of human chromosome 2 in the region p23-p24 to which the apoB gene has been assigned. Since the Ag(x) antigen is associated with altered plasma lipid levels, this determinant may indicate a functionally important domain of apoB.