Characterization of a new apolipoprotein E5 variant detected in two French-Canadian subjects

Mailly, F; Xu, CF; Xhignesse, M; Lussier-Cacan, S; Talmud, PJ; Davignon, J; Humphries, SE; Nestruck, AC

doi:10.1016/s0022-2275(20)42048-6

Cited by 36Lipoproteins and Cardiovascular HealthLipid metabolism and disordersCholesterol and Lipid Metabolism

Characterization of a new apolipoprotein E5 variant detected in two French-Canadian subjects

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Mailly, F, Xu, CF, Xhignesse, M, Lussier-Cacan, S, Talmud, PJ, Davignon, J, Humphries, SE, Nestruck, AC·1991·Journal of Lipid Research

DOI 10.1016/s0022-2275(20)42048-6

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Abstract

We have found a novel apoE5 mutation, using isoelectric focusing (IEF), in two apparently unrelated French-Canadian subjects. Co-dominant inheritance was demonstrated in the family of the first proband, a healthy male subject. The presence of the apoE5 form was not associated with lipid abnormalities or cardiovascular disease in this family. The second proband was a hyperlipidemic female patient suffering from angina, with no informative relatives available for study. In both individuals, monoclonal antibody studies demonstrated that the mutation was associated with the loss of two overlapping epitopes at the amino terminus of the protein. Cysteamine treatment of the very low density lipoproteins indicated that the mutant apoE contained only one cysteine residue, suggesting that apoE3 was the parental form. Two-dimensional electrophoresis suggested that the mutated protein had a slightly lower molecular weight (by 1-2 kDa). However, DNA sequencing of the third exon of the apoE gene in both probands revealed a single G to A substitution at the 48th nucleotide, changing the amino acid at position 13 from glutamic acid to lysine. These results were confirmed by oligo melting experiments with allele-specific probes in relatives of the probands. The study of this apoE variant should provide additional insight into the structure-function relationship of apoE.

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CHARACTERIZATION OF A NEW APOLIPOPROTEIN-E5 VARIANT DETECTED IN 2 FRENCH-CANADIAN SUBJECTS
Mailly, F., Xu, C., XHIGNESSE, M., LUSSIERCACAN, S., Talmud, P., Davignon, J., Humphries, S. E., & Nestruck, A. C. (1991) · UCL Discovery (University College London)
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Authors: Mailly, F., Xu, C., Xhignesse, M., Lussier-Cacan, S., Talmud, P., Davignon, J., Humphries, S., & Nestruck, A.
Affiliations: Montreal Clinical Research Institute (CA)
ORCID: Xhignesse, M
Davignon, J
Venue: Journal of Lipid Research
Publisher: Elsevier BV
Published: 1991-04
Volume: 32
Issue: 4
Pages: 613-620
ISSN: 0022-2275 (ISSN-L)
DOI: 10.1016/s0022-2275(20)42048-6
OpenAlex: W2411978561
Semantic Scholar: 8f0928506decced1c9afbb937ba9f998a074e6dc
Cited by: 36
References: 45
Citations by year: 2023: 7 · 2021: 1 · 2018: 1 · 2015: 1 · 2014: 1 · 2013: 2
FWCI: 4.36
Type: journal article
Language: en
Open access: hybrid
doi.org
Licence: cc-by
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/legal/tdmrep-license (tdm)
creativecommons.org/licenses/by/4.0/ (vor, 10786 d)
Locations: Journal of Lipid Research (publishedVersion, cc-by)
PubMed (publishedVersion)
DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Topics: Health Sciences › Medicine › Surgery › Lipoproteins and Cardiovascular Health
Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Lipid metabolism and disorders
Health Sciences › Medicine › Surgery › Cholesterol and Lipid Metabolism
Keywords: codominant inheritance, hyperlipidemia, angina pectoris, epitope loss, APOE3, structure-function relationship, French-Canadian population
MeSH terms: Adult, Alleles, Amino Acid Sequence, Epitopes, Apolipoproteins E, Base Sequence, Female, Humans, Hyperlipidemia, Familial Combined, Lipoproteins, VLDL, Male, Middle Aged, Molecular Sequence Data, Mutation, Pedigree, Genetic Variation

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Characterization of a new apolipoprotein E5 variant detected in two French-Canadian subjects

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