Low density lipoprotein ligand-receptor interactions in normal healthy individuals characterized by their XbaI...

A DNA restriction fragment length polymorphism (RFLP), observed with the XbaI restriction enzyme digestion of peripheral lymphocyte genomic DNA and a 3.5 kb probe 3' end of the apolipoprotein B gene, was investigated in 228 normal healthy males. Lipoprotein measurements were conducted on fasting plasma and related to the genotype; the X2X2 homozygotes (the X2 allele contains the enzyme cutting site) had significantly higher plasma cholesterol, low density (LDL) cholesterol and LDL apolipoprotein B. Thirty subjects (10 from each of the X1X1, X1X2 and X2X2 groups) were recalled and the LDL receptor activity measurements, conducted on peripheral venous blood lymphocytes, indicated no significant differences between the genotypes. However, when LDLs isolated from these individuals were assayed for ligand-receptor interaction with a human embryonic lung fibroblast cell line, significantly different maximum binding (Bmax) values in the X2 allele-bearing individuals were observed. This paradoxically elevated in vitro binding and degradation of LDL from X2X2 subjects suggests that the elevated concentrations of LDL cholesterol observed with this genotype in vivo does not result from a defective ligand-receptor interaction directly related to this polymorphism.