Genetics of the low density lipoprotein receptor:

Fibroblast association (plasma membrane binding plus intracellular accumulation) and degradation of radioiodinated low density lipoprotein (125I‐LDL) index plasma membrane LDL receptor activity. Cultured fibroblasts from 23 subjects affected with familial hypercholesterolemia (HC) and from 95 subjects without HC (non‐HCs) were tested for 125I‐LDL association and degradation. Both LDL receptor activity indices were twice as high in non‐HC and HC heterozygous cell strains. This is compatible with a major gene effect on LDL receptor activity. However, a considerable overlap between non‐HC and HC heterozygous values was found in the 125I‐LDL association assay [median (range) 970 (330–2500), and 450 (250–940), respectively] and in the degradation assay [median (range) 810 (280–2020), and 470 (160–790), respectively]. The values are expressed as ng 125I‐LDL mg cell protein‐14.5 h‐1.These great overlaps in the LDL receptor activity indices support the view that the influence of LDL receptor activity on the HC phenotype may be smaller than believed previously. Furthermore, for the diagnosis of HC, these LDL receptor activity assays are far more expensive and have less sensitivity and speci