title: Genetics of the low density lipoprotein receptor: I. Low density lipoprotein receptor activity in cultured fibroblasts from subjects with or without familial hypercholesterolemia.
abstract: Six indices of low density lipoprotein (LDL) receptor activity were assayed in cultured fibroblasts from seven subjects with familial hypercholesterolemia (HC) and six subjects without HC (non-HCs). Four non-HCs, three HC heterozygotes and one HC homozygous proband belonged to one kindred (kindred A). The proband's fibroblast 125I-LDL processing values fell within or were slightly above the range defined by fibroblasts from three "receptor-negative" HC homozygotes. Thus, the plasma membrane receptor defect in this kindred is probably of the "receptor-negative" category. LDL receptor-dependent 125I-LDL processing was about twice as high in fibroblasts from non-HCs as in those from HC heterozygotes belonging to kindred A. The segregation pattern of LDL receptor activity in this kindred was compatible with control by a single gene locus. 125I-LDL processing values from non-HCs, HC heterozygotes and HC homozygotes differed significantly from one another, but non-HCs and HC heterozygotes showed some overlap. LDL receptor-dependent 125I-LDL association (plasma membrane binding plus intracellular accumulation) data for 6 HC heterozygous and 13 non-HC fibroblast strains clustered into two and into three groups, respectively. Median 125I-LDL association levels in these groups appeared to be in agreement with hypothesis that two different geno-types in HC heterozygotes and three in non-HCs determined LDL receptor activity. These findings suggest the possibility that 125I-LDL processing studies may reveal "normal" alleles at the LDL receptor locus.
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D002478:Cells, Cultured; D002648:Child; D005260:Female; D005347:Fibroblasts / Q000378:metabolism; D006801:Humans; D006938:Hyperlipoproteinemia Type II / Q000378:metabolism*; D008077:Lipoproteins, LDL / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D010375:Pedigree; D011956:Receptors, Cell Surface / Q000235:genetics*; D018110:Receptors, Lipoprotein
chemical_list: D008077:Lipoproteins, LDL; D011956:Receptors, Cell Surface; D018110:Receptors, Lipoprotein