Apolipoprotein B-100 Hopkins (Arginine4019 [unk] Tryptophan)

Abstract

A 43-year-old woman with severe coronary artery disease and hyperapobetalipoproteinemia was heterozygous for an abnormal Msp I apolipoprotein B (APOB) gene fragment because of the absence of the MspI site around codon 4046 in exon 29 of the APOB gene. Using the polymerase chain reaction technique, 134 base pairs containing the mutant Msp I site were amplified, cloned, and sequenced. The mutation was a C to T transition, substituting tryptophan for arginine at amino acid position 4019 of the mature ApoB-100 protein. Seven relatives of the proband had the same mutation, which has been called "ApoB-100 Hopkins." Only three of seven relatives with the mutation had hyperapobetalipoproteinemia; one was borderline while two other relatives without the mutation had hyperapobetalipoproteinemia. Mutant low-density lipoprotein (LDL) was bound and degraded to a greater extent than normal LDL in cultured human fibroblasts. In conclusion, a new mutation, ApoB-100 Hopkins, was not linked to the hyperapobetalipoproteinemia phenotype, which also was segregating in this family. The increased affinity of this mutant LDL for the LDL receptor may be due to a specific effect of ApoB-100 Hopkins or to altered LDL size and composition.

DNA polymorphism haplotypes of the human lipoprotein lipase gene: possible association with high density lipoprotein levels

“…The concentrations of apolipoprotein B (apoB) and apolipoprotein A-I (apoA-I), were measured by radial immunodiffusion as described elsewhere (Kwiterovich et al 1987;Ladias et al 1989).…”

“…DNA was isolated from blood cells as previously described (Ladias et al 1989). Five I~g of the DNA was then digested with various restriction enzymes, subjected electrophoresis through 1% agarose gel and transferred to nylon membranes as described ).…”

“…The subjects were on a regular diet and none were taking lipid-lowering medications. A detailed description of this study is presented in Ladias et al (1989).…”