Apolipoprotein B gene mutations in Austrian subjects with heart disease and their kindred.

In a group of 110 subjects with severe coronary artery disease, two were heterozygous for the apolipoprotein (apo) B arginine3,500----glutamine mutation that characterizes familial defective apo B-100. Both affected subjects were moderately hypercholesterolemic, and their low density lipoproteins (LDLs) were deficient in binding to the LDL receptor. Pedigree analysis of the two probands' families established a correlation between the apo B mutation, defective LDL, and a particular apo B haplotype that was characterized by 10 apo B gene markers. In addition to having one allele carrying the arginine3,500----glutamine mutation, one family member may harbor a second mutant apo B allele that causes its gene product to be present in plasma at a lower than normal level, despite the fact that the affinity of the protein for the LDL receptor appears to be normal. The metabolic basis for the underrepresentation of this second allotype remains to be elucidated.