Detection of a new apolipoprotein-E mutation in type III hyperlipidemia using deoxyribonucleic acid restriction isotyping
Abstract
While determining the apolipoprotein-E (apo-E) genotype of 22 patients with type III hyperlipidemia (HLP III) by restriction isotyping, we identified a new mutant form of apo-E by its unusual DNA restriction fragment length polymorphism pattern. DNA sequence analysis of a polymerase chain reaction-amplified portion of the proband's apo-E gene revealed the substitution of cysteine (TGC) for arginine (CGC) at position 136 in the mutant allele (designated R136C). Lipoproteins containing this mutant protein bound defectively to macrophages in vitro, confirming the contribution of R136C to the expression of HLP III in the proband. The proband's two siblings carried the mutant allele and were also heterozygous for E2. Each also had dysbetalipoproteinemia (indicated by the presence of beta-very low density lipoprotein), but neither was hyperlipidemic, attesting to the importance of other factors for the full expression of HLP III. The mutant allele appears to contribute to the inheritance of HLP III in a recessive fashion. Restriction isotyping facilitates the diagnosis of subjects with HLP III, aids in the identification of affected individuals through family screening, and can contribute to the discovery of new mutations that help explain the pathogenesis of HLP III.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Walden et al. confirmed the FD phenotype by electrophoresis in heterozygous p.Arg154Ser and p.Arg176Cys carriers and showed in vitro that abnormal cell binding contributes to dysbetalipoproteinemia.
“Walden et al. [46] confirmed the FD phenotype by electrophoresis in heterozygous p.Arg154Ser and p.Arg176Cys carriers and showed in vitro that abnormal cell binding contributes to dysbetalipoproteinemia.”
From Spectrum and Prevalence of Rare APOE Variants and Their Association with Familial Dysbetalipoproteinemia (2024) · cites this paper as [46]
p.Arg154Cys is located in the critical APOE domain and alters the amino acid residue in which another variant, p.Arg154Ser, was found to be likely pathogenic for FD.
“This variant is located in the critical APOE domain [45,46] and alters the amino acid residue, in which another variant, p.Arg154Ser, was found to be likely pathogenic for FD [5,29,47].”
From Spectrum and Prevalence of Rare APOE Variants and Their Association with Familial Dysbetalipoproteinemia (2024) · cites this paper as [46]
Cites
Apolipoprotein E polymorphism and atherosclerosis.
Davignon, J., Gregg, R. E., & Sing, C. F. (1988) · Arteriosclerosis: An Official Journal of the American Heart Association, Inc. · doi:10.1161/01.atv.8.1.1 · Cited by 1,981 · see citing works
Human apolipoprotein E. The complete amino acid sequence
Rall, S. C., Weisgraber, K. H., & Mahley, R. W. (1982) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)34702-1 · Cited by 741 · see citing works
Three-Dimensional Structure of the LDL Receptor-Binding Domain of Human Apolipoprotein E
Wilson, C., Wardell, M. R., Weisgraber, K. H., Mahley, R. W., & Agard, D. A. (1991) · Science · doi:10.1126/science.2063194 · Cited by 678 · see citing works
Proposed nomenclature of apoE isoproteins, apoE genotypes, and phenotypes
Zannis, V. I., Breslow, J. L., Utermann, G., Mahley, R. W., Weisgraber, K. H., Havel, R. J., Goldstein, J. L., Brown, M. S., Schonfeld, G., Hazzard, W. R., et al. (1982) · Journal of Lipid Research · doi:10.1016/s0022-2275(20)38094-9 · Cited by 436 · see citing works
Rall, S. C., Weisgraber, K. H., Innerarity, T. L., & Mahley, R. W. (1982) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.79.15.4696 · Cited by 345 · see citing works
Wardell, M. R., Brennan, S. O., Janus, E. D., Fraser, R., & Carrell, R. W. (1987) · Journal of Clinical Investigation · doi:10.1172/jci113096 · Cited by 159 · see citing works
Wardell, M. R., Weisgraber, K. H., Havekes, L. M., & Rall, S. C. (1989) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(19)30067-5 · Cited by 80 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Mahley, R. W., Huang, Y., & Rall, S. C. (1999) · Journal of Lipid Research · doi:10.1016/s0022-2275(20)32417-2 · Cited by 447 · see citing works
APOE gene variants in primary dyslipidemia
Khalil, Y. A., Rabès, J.-P., Boileau, C., & Varret, M. (2021) · Atherosclerosis · doi:10.1016/j.atherosclerosis.2021.05.007 · Cited by 170 · see citing works
Pocovi, M., Cenarro, A., Civeir, F., Myers, R. H., Casao, E., Esteban, M., & Ordovas, J. M. (1996) · Atherosclerosis · doi:10.1016/0021-9150(95)06745-0 · Cited by 42 · see citing works
Feussner, G., Albanese, M., & Valencia, A. (1996) · Atherosclerosis · doi:10.1016/0021-9150(96)05870-4 · Cited by 7 · see citing works
Blokhina, A. V., Ershova, A. I., Kiseleva, A. V., Sotnikova, E. A., Zharikova, A. A., Zaicenoka, M., Vyatkin, Y. V., Ramensky, V. E., Kutsenko, V. A., Garbuzova, E. V., et al. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms252312651 · Cited by 8 · see citing works
- Authors
- Walden, C. C., Huff, M. W., Leiter, L. A., Connelly, P. W., & Hegele, R. A.
- Affiliations
- St. Michael's Hospital (CA)
- Venue
- The Journal of Clinical Endocrinology & Metabolism
- Publisher
- The Endocrine Society
- Published
- 1994-03
- Volume
- 78
- Issue
- 3
- Pages
- 699-704
- ISSN
- 0021-972X (ISSN-L)
- 1945-7197
- OpenAlex
- W1965141338
- Cited by
- 26
- References
- 7
- Citations by year
- 2024: 1 · 2023: 1 · 2021: 1 · 2020: 1 · 2016: 1 · 2015: 1
- FWCI
- 1.58
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The Journal of Clinical Endocrinology & Metabolism (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Lipid metabolism and disorders
- Health Sciences › Medicine › Surgery › Lipoproteins and Cardiovascular Health
- Health Sciences › Medicine › Surgery › Cholesterol and Lipid Metabolism
- Keywords
- apolipoprotein E, type III hyperlipidemia, apolipoprotein E gene, restriction fragment length polymorphism, dysbetalipoproteinemia, beta-VLDL, macrophage binding, recessive inheritance, family screening, genetic diagnosis
- MeSH terms
- Adult, Aged, Alleles, Apolipoproteins E, Base Sequence, DNA, Female, Genotype, Humans, Hyperlipoproteinemia Type III, Male, Molecular Sequence Data, Mutation, Pedigree, Phenotype, Polymorphism, Restriction Fragment Length, Polymerase Chain Reaction
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
