Apolipoprotein B-100 Hopkins (Arginine4019 ➧ Tryptophan)

A New Apolipoprotein B-100 Variant in a Family With Premature Atherosclerosis and Hyperapobetalipoproteinemia

John A A Ladias, Peter O. Kwiterovich, Hazel H. Smith, Michael Miller, Paul S. Bachorik, Trudy Forte, Aldons J. Lusis, Stylianos E. Antonarakis

Research output: Contribution to journalArticle

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 Msp I 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.

Original languageEnglish (US)
Pages (from-to)1980-1988
Number of pages9
JournalJournal of the American Medical Association
Volume262
Issue number14
DOIs
StatePublished - Oct 13 1989

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Apolipoprotein B-100
Tryptophan
Atherosclerosis
LDL Lipoproteins
Mutation
Apolipoproteins B
LDL Receptors
Codon
Base Pairing
Genes
Arginine
Coronary Artery Disease
Exons
Fibroblasts
Phenotype
Amino Acids
Polymerase Chain Reaction
Proteins

ASJC Scopus subject areas

  • Medicine(all)

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Apolipoprotein B-100 Hopkins (Arginine4019 ➧ Tryptophan) : A New Apolipoprotein B-100 Variant in a Family With Premature Atherosclerosis and Hyperapobetalipoproteinemia. / Ladias, John A A; Kwiterovich, Peter O.; Smith, Hazel H.; Miller, Michael; Bachorik, Paul S.; Forte, Trudy; Lusis, Aldons J.; Antonarakis, Stylianos E.

In: Journal of the American Medical Association, Vol. 262, No. 14, 13.10.1989, p. 1980-1988.

Research output: Contribution to journalArticle

Ladias, John A A ; Kwiterovich, Peter O. ; Smith, Hazel H. ; Miller, Michael ; Bachorik, Paul S. ; Forte, Trudy ; Lusis, Aldons J. ; Antonarakis, Stylianos E. / Apolipoprotein B-100 Hopkins (Arginine4019 ➧ Tryptophan) : A New Apolipoprotein B-100 Variant in a Family With Premature Atherosclerosis and Hyperapobetalipoproteinemia. In: Journal of the American Medical Association. 1989 ; Vol. 262, No. 14. pp. 1980-1988.
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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 Msp I 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.",
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