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Apolipoprotein E2-Christchurch (136 Arg----Ser). New variant of human apolipoprotein E in a patient with type III hyperlipoproteinemia.
Open accessAbstract
The primary structure of apolipoprotein E (apo E) was investigated in seven type III hyperlipoproteinemic patients with the apo E-2/2 phenotype. Six of the patients had identical two-dimensional tryptic peptide maps. These differed from the normal apo E3 map by the altered mobility of a single peptide. Amino acid analysis and sequencing showed that apo E2 in these patients had a substitution of 158 Arg----Cys. The presence of this mutation in six of the seven type III patients confirms that this is the most common form of apo E2. The seventh type III patient had a unique map with a new peptide resulting from a substitution of 136 Arg----Ser. He was heterozygous for this and for the more common apo E2 (158 Arg----Cys) variant. His very low-density lipoprotein contained approximately five times more apo E2 (136 Arg----Ser) than apo E2 (158 Arg----Cys), as determined by cysteamine treatment and peptide mapping. This new apo E2 mutant thus appears to contribute significantly to the patient's hyperlipidemia.
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In the paper
“This is significant because the heparin-binding and receptor-binding domains coincide (59).”
§ Apolipoprotein E2-Christchurch (136 Arg --Ser) New Variant of Human Apolipoprotein E in a Patient with Type III Hyperlipoproteinemia > Discussion
What the sources say
- Supportedcites [59] 59. Weisgraber, K. H., S. C. Rall, Jr., R. W. Mahley, R. W. Milne, Y. L. Marcell, and J. T. Sparrow. 1986. Human apolipoprotein E: de- termination of the heparin binding sites of apolipoprotein E3. J. Biol. Chem. 261:2068-2076. source
The Discussion (page unavailable) places apo-E3’s first heparin-binding site, at residues 142–147, in the same region as its lipoprotein receptor-binding domain. It also identifies a second heparin-binding site elsewhere, so the coincidence refers to the first site. (LLM, conf=0.90)
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In the paper
“When quantitative amino acid analysis was performed on her two peptides, T17Ch and T17, the ratio was found to be 1.5:1.”
§ Apolipoprotein E2-Christchurch (136 Arg --Ser) New Variant of Human Apolipoprotein E in a Patient with Type III Hyperlipoproteinemia > Results
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In the paper
“The seventh type III patient had a unique map with a new peptide resulting from a substitution of 136 Arg --Ser.”
§ Apolipoprotein E2-Christchurch (136 Arg --Ser) New Variant of Human Apolipoprotein E in a Patient with Type III Hyperlipoproteinemia > Abstract
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In the paper
“The seventh type III patient was heterozygous for this and for a new variant, apo E2 (136 Arg --Ser).”
§ Apolipoprotein E2-Christchurch (136 Arg --Ser) New Variant of Human Apolipoprotein E in a Patient with Type III Hyperlipoproteinemia > Discussion
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In the paper
“The ratio of T17Ch to T17 was 4.8:1”
§ Apolipoprotein E2-Christchurch (136 Arg --Ser) New Variant of Human Apolipoprotein E in a Patient with Type III Hyperlipoproteinemia > Results
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In the paper
“Amino acid analysis and sequencing showed that apo E2 in these patients had a substitution of 158 Arg --Cys.”
- Also stated in: § Results · boosted
“confirming the substitution as 158 Arg --Cys.”
§ Apolipoprotein E2-Christchurch (136 Arg --Ser) New Variant of Human Apolipoprotein E in a Patient with Type III Hyperlipoproteinemia > Abstract
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“His very low-density lipoprotein contained approximately five times more apo E2 (136 Arg -Ser) than apo E2 (158 Arg --Cys), as determined by cysteamine treatment and peptide mapping.”
§ Apolipoprotein E2-Christchurch (136 Arg --Ser) New Variant of Human Apolipoprotein E in a Patient with Type III Hyperlipoproteinemia > Abstract
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In the paper
“The expected initial sequence of Leu-Ala was confirmed for T 17”
§ Apolipoprotein E2-Christchurch (136 Arg --Ser) New Variant of Human Apolipoprotein E in a Patient with Type III Hyperlipoproteinemia > Results
plainSingle case- Asserted: passes — The authors put it forward as true.
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In the paper
“that of TI 7Ch was Val-Ser-Leu”
§ Apolipoprotein E2-Christchurch (136 Arg --Ser) New Variant of Human Apolipoprotein E in a Patient with Type III Hyperlipoproteinemia > Results
plainSingle case- Asserted: passes — The authors put it forward as true.
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In the paper
“that T17Ch contained two additional amino acids, valine and serine.”
§ Apolipoprotein E2-Christchurch (136 Arg --Ser) New Variant of Human Apolipoprotein E in a Patient with Type III Hyperlipoproteinemia > Results
plainSingle case- Asserted: passes — The authors put it forward as true.
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- It may state two separate claims as one. 29
- Probably not a substantial claim. 12
The sources with a verdict support this claim; the rest weren’t checked yet, have no full text we could read, or their verdicts aren’t rated yet.
In the paper
“The most common has a mutation of 158 Arg --Cys (13), but mutations of 145 Arg -* Cys (14) and 146 Lys --Gln (6) have also been reported in individuals with type III hyperlipoproteinemia.”
§ Apolipoprotein E2-Christchurch (136 Arg --Ser) New Variant of Human Apolipoprotein E in a Patient with Type III Hyperlipoproteinemia > Introduction
What the sources say
- Not checked — no full text of the sourcecites [13] 13. Rall, S. C., Jr., K. H. Weisgraber, and R. W. Mahley. 1982. Human apolipoprotein E. The complete amino acid sequence. J. Biol. Chem. 257:4171-4178. source
- Not checked — no full text of the sourcecites [14] 14. Rall, S. C., Jr., K. H. Weisgraber, T. L. Innerarity, and R. W. Mahley. 1982. Structural basis for receptor binding heterogeneity ofapo- lipoprotein E from type III hyperlipoproteinemic subjects. Proc. Natl. Acad. Sci. USA. 79:4696-4700. source
- Supportedcites [6] 6. Rall, S. C., Jr., K. H. Weisgraber, T. L. Innerarity, T. P. Bersot, R. W. Mahley, and C. B. Blum. 1983. Identification of a new structural variant of human apolipoprotein E, E2(Lys 146 -* Gln), in a type III hyperlipoproteinaemic subject with the E-3/2 phenotype. J. Clin. Invest. 72:1288-1297. source
The citation is attached to the 146 Lys-to-Gln mutation, not the other variants in the sentence. The Discussion describes that substitution, and the Apolipoprotein E2(Lys146-Gln) section states that it was identified in two individuals with type III hyperlipoproteinemia. Page numbers are not provided in our copy. (LLM, conf=0.94)
plain- Asserted: passes — The authors put it forward as true.
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The sources with a verdict support this claim; the rest weren’t checked yet, have no full text we could read, or their verdicts aren’t rated yet.
In the paper
“Affected subjects are often homozygous for apo E2, but hetero- zygosity for this variant has also been reported in association with this disease (4)(5)(6)(7)(8).”
§ Apolipoprotein E2-Christchurch (136 Arg --Ser) New Variant of Human Apolipoprotein E in a Patient with Type III Hyperlipoproteinemia > Introduction
What the sources say
- Not checked — no full text of the sourcecites [4] 4. Breslow, J. L., V. I. Zannis, T. R. SanGiacomo, J. L. Third, T. Tracy, and C. J. Glueck. 1982. Studies offamilial type III hyperlipopro- teinaemia using as a genetic marker the apoE phenotype E2/2. J. Lipid Res. 23:1224-1235. source
- Not checked — no full text of the sourcecites [5] 5. Zannis, V. I., and J. L. Breslow. 1985. Genetic mutations affecting human lipoprotein metabolism. Adv. Hum. Genet. 14:125-215 and 383- 386. source
- Supportedcites [6] 6. Rall, S. C., Jr., K. H. Weisgraber, T. L. Innerarity, T. P. Bersot, R. W. Mahley, and C. B. Blum. 1983. Identification of a new structural variant of human apolipoprotein E, E2(Lys 146 -* Gln), in a type III hyperlipoproteinaemic subject with the E-3/2 phenotype. J. Clin. Invest. 72:1288-1297. source
The Introduction says type III hyperlipoproteinemia is usually associated with the E2/2 phenotype. The characterization of subject D.F. identifies a person with the disease who had the heterozygous E3/2 phenotype, and the discussion identifies the E2 variant as E2(Lys146-Gln). Page numbers are not provided for these passages. (LLM, conf=0.94)
plaincorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“The first of these, apo B,E or low-density lipoprotein (LDL) receptor, is present in most tissues.Apo E has a much higher affinity than apolipoprotein B for this receptor because of the potential of apo E-containing particles to form multiple interactions with several sites on the receptor (15)(16)(17).”
§ Apolipoprotein E2-Christchurch (136 Arg --Ser) New Variant of Human Apolipoprotein E in a Patient with Type III Hyperlipoproteinemia > Introduction
What the sources say
- Partly supportedcites [15] 15. Pitas, R. E., T. L. Innerarity, K. S. Arnold, and R. W. Mahley. 1979. Rate and equilibrium constants for binding of apo-E HDLc (a cholesterol-induced lipoprotein) and low density lipoproteins to human fibroblasts: evidence for multiple receptor binding of apo-E HDLc. Proc. Natl. Acad. Sci. USA. 76:2311-2315. sourceExperimental — accuracy not yet measured
The Results report that apo-E HDLc had 23-fold higher affinity than LDL for receptors on human fibroblasts. The Discussion says that multiple recognition sites on an HDLc particle can interact with multiple receptors—not that the particle interacts with several sites on one receptor. The paper studies fibroblasts and does not establish that the receptor is present in most tissues. (LLM, conf=0.88)
- Not checked — no full text of the sourcecites [16] 16. Innerarity, T. L., and R. W. Mahley. 1978. Enhanced binding by cultured human fibroblasts of apo-E-containing lipoproteins as com- pared with low density lipoproteins. Biochemistry. 17:1440-1447. source
- Not checked — no full text of the sourcecites [17] 17. Innerarity, T. L., E. S. Kempner, D. Y. Hui, and R. W. Mahley. 1981. Functional unit ofthe low density lipoprotein receptor offibroblasts: a 100,000-dalton structure with multiple binding sites. Proc. Natl. Acad. Sci. USA. 78:4378-4382. source
plaindirect- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
- Partly supported
The sources with a verdict support this claim; the rest weren’t checked yet, have no full text we could read, or their verdicts aren’t rated yet.
In the paper
“Three variants ofapo E2 have been described.Each ofthese differs from apo E3 by a single amino acid substitution (6, 12- 14).”
§ Apolipoprotein E2-Christchurch (136 Arg --Ser) New Variant of Human Apolipoprotein E in a Patient with Type III Hyperlipoproteinemia > Introduction
What the sources say
- Supportedcites [6] 6. Rall, S. C., Jr., K. H. Weisgraber, T. L. Innerarity, T. P. Bersot, R. W. Mahley, and C. B. Blum. 1983. Identification of a new structural variant of human apolipoprotein E, E2(Lys 146 -* Gln), in a type III hyperlipoproteinaemic subject with the E-3/2 phenotype. J. Clin. Invest. 72:1288-1297. source
Table VII lists three apo E2 variants, each with one amino acid substitution relative to apo E3. The Discussion also calls E2(Lys146-Gln) the third structurally different apo E2. Page numbers are not provided in our copy. (LLM, conf=0.94)
- Not checked — no full text of the sourcecites [12] 12. Weisgraber, K. H., S. C. Rall, Jr., and R. W. Mahley. 1981. Human E apoprotein heterogeneity. Cysteine-arginine interchanges in the amino acid sequence of the apo-E isoforms. J. Biol. Chem. 256: 9077-9083. source
- Not checked — no full text of the sourcecites [13] 13. Rall, S. C., Jr., K. H. Weisgraber, and R. W. Mahley. 1982. Human apolipoprotein E. The complete amino acid sequence. J. Biol. Chem. 257:4171-4178. source
- Not checked — no full text of the sourcecites [14] 14. Rall, S. C., Jr., K. H. Weisgraber, T. L. Innerarity, and R. W. Mahley. 1982. Structural basis for receptor binding heterogeneity ofapo- lipoprotein E from type III hyperlipoproteinemic subjects. Proc. Natl. Acad. Sci. USA. 79:4696-4700. source
plain- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. The paper’s conclusions may not depend on it.
- Supported
The sources with a verdict support this claim; the rest weren’t checked yet, have no full text we could read, or their verdicts aren’t rated yet.
In the paper
“Individual cases of type III have also been observed in association with the apo E-3/3 phenotype (9) and in an individual with a deficiency of apo E (10).”
§ Apolipoprotein E2-Christchurch (136 Arg --Ser) New Variant of Human Apolipoprotein E in a Patient with Type III Hyperlipoproteinemia > Introduction
What the sources say
- Supportedcites [9] 9. Havel, R. J., L. Kotite, J. P. Kane, P. Tun, and T. Bersot. 1983. Atypical familial dysbetalipoproteinemia associated with apolipoprotein phenotype E3/3. J. Clin. Invest. 72:379-387. source
Citation (9) is attached to the E3/3 observation, not the separate apo E-deficiency case cited as (10). The Abstract (page unavailable) reports typical dysbetalipoproteinemia in five family members whose apo E phenotype was E3/3. (LLM, conf=0.94)
- Not checked — no full text of the sourcecites [10] 10. Ghiselli, G., E. J. Schaefer, P. Gascon, and H. B. Brewer, Jr. 1981. Type III hyperlipoproteinemia associated with apolipoprotein E deficiency. Science (Wash. DC). 214:1239-1241. source
plaincorrelational- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Peptide T22 was missing in six of the seven homozygous apo E2 type III patients and was replaced by a new peptide containing tyrosine and sulphur.”
§ Apolipoprotein E2-Christchurch (136 Arg --Ser) New Variant of Human Apolipoprotein E in a Patient with Type III Hyperlipoproteinemia > Results
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In the paper
“As expected, cyste- amine treatment caused the apo E-3/3 isoform pattern ofF.J.T. to shift toward the cathode, and thus to resemble the apo E-4/ 4 phenotype.This indicated the presence ofone cysteine residue (data not shown).”
§ Apolipoprotein E2-Christchurch (136 Arg --Ser) New Variant of Human Apolipoprotein E in a Patient with Type III Hyperlipoproteinemia > Results
hedgeddirectSingle case- Asserted: passes — The authors put it forward as true.
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In the paper
“Both cysteamine treatment and peptide mapping indicated a considerable excess of apo E2 (136 Arg -* Ser) over the usual apo E2 gene product.”
- Also stated in: § Results · plain
“This was confirmed by quantitative elution and amino acid analysis of the appropriate peptides.”
§ Apolipoprotein E2-Christchurch (136 Arg --Ser) New Variant of Human Apolipoprotein E in a Patient with Type III Hyperlipoproteinemia > Results
plainSingle case- Asserted: passes — The authors put it forward as true.
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- Also stated in: § Results · plain
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“As yet she does not exhibit any symptoms of type III hyperlipoproteinemia, although her plasma triglyceride has increased from 1.4 to 3.8 mmol/liter.”
§ Apolipoprotein E2-Christchurch (136 Arg --Ser) New Variant of Human Apolipoprotein E in a Patient with Type III Hyperlipoproteinemia > Results
plainSingle case- Asserted: passes — The authors put it forward as true.
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In the paper
“The im- plied new cysteine in CM-T22* was confirmed by amino acid, N-terminal, and sequence analysis.A sequence/composition of CM-Cys-Leu-Ala, Val, Tyr, Gln, Ala, Gly, Ala, Arg was estab- lished for this aberrant peptide.”
§ Apolipoprotein E2-Christchurch (136 Arg --Ser) New Variant of Human Apolipoprotein E in a Patient with Type III Hyperlipoproteinemia > Results
plainSingle case- Asserted: passes — The authors put it forward as true.
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In the paper
“Initial sequences of Leu-Ala-Val and CM-Cys-Leu-Ala respectively were ob- tained for these peptides, confirming the substitution as 158 Arg --Cys.”
§ Apolipoprotein E2-Christchurch (136 Arg --Ser) New Variant of Human Apolipoprotein E in a Patient with Type III Hyperlipoproteinemia > Results
boosteddirectSingle case- Asserted: passes — The authors put it forward as true.
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“After cys- teamine modification, a major apo E isoprotein changed its mi- gration by only one charge towards the cathode, whereas a minor band focused two charge units more cathodally (Fig. 1 B).This indicated the presence of two apo E2 proteins: one”
§ Apolipoprotein E2-Christchurch (136 Arg --Ser) New Variant of Human Apolipoprotein E in a Patient with Type III Hyperlipoproteinemia > Results
hedgeddirectSingle case- Asserted: passes — The authors put it forward as true.
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In the paper
“At the age of ten, K.T. had an elevated cholesterol level, but now, five years later, her cholesterol is normal (4.4 mmol/liter).”
§ Apolipoprotein E2-Christchurch (136 Arg --Ser) New Variant of Human Apolipoprotein E in a Patient with Type III Hyperlipoproteinemia > Results
plainSingle case- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“J.W.T. had a unique peptide map that differed from the other type III maps in two respects.First, T22 was present in addition to CM-T22*, the former being present in substantially higher yield.Second, a completely new basic peptide (T17Ch) was observed with a mobility of +0.65 relative to aspartic acid (Fig. 2 C).”
§ Apolipoprotein E2-Christchurch (136 Arg --Ser) New Variant of Human Apolipoprotein E in a Patient with Type III Hyperlipoproteinemia > Results
plainSingle case- Asserted: passes — The authors put it forward as true.
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The seventh was hetero- zygous for this and for a new apo E2, apo E2 (136 Arg Ser), which was the predominant VLDL isoform in this subject.”
§ Apolipoprotein E2-Christchurch (136 Arg --Ser) New Variant of Human Apolipoprotein E in a Patient with Type III Hyperlipoproteinemia > Introduction
plainSingle case- Asserted: passes — The authors put it forward as true.
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“J.W.T. was heterozygous for this mutation and for one in- volving peptide T1 7.”
§ Apolipoprotein E2-Christchurch (136 Arg --Ser) New Variant of Human Apolipoprotein E in a Patient with Type III Hyperlipoproteinemia > Results
plainSingle case- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“This new peptide stained slowly with cadmium-ninhydrin suggesting a valine N-terminal (36) and it also stained positively for histidine and arginine.”
§ Apolipoprotein E2-Christchurch (136 Arg --Ser) New Variant of Human Apolipoprotein E in a Patient with Type III Hyperlipoproteinemia > Results
hedgedcorrelationalSingle case- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Peptide T22 is missing and replaced by a new neu- tral peptide, CM-T22*.”
§ Apolipoprotein E2-Christchurch (136 Arg --Ser) New Variant of Human Apolipoprotein E in a Patient with Type III Hyperlipoproteinemia > Discussion
plainSingle case- Asserted: passes — The authors put it forward as true.
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In the paper
“A fascinating feature of this case is that the product of the apo E2-Christchurch gene comprises 80% of the apo E in J.W.T.'s VLDL, the remaining 20% being apo E2 (158 Arg Cys).”
§ Apolipoprotein E2-Christchurch (136 Arg --Ser) New Variant of Human Apolipoprotein E in a Patient with Type III Hyperlipoproteinemia > Discussion
plainSingle case- Asserted: passes — The authors put it forward as true.
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In the paper
“The primary structures of nine apo E isoproteins have now been determined (Table IV).”
§ Apolipoprotein E2-Christchurch (136 Arg --Ser) New Variant of Human Apolipoprotein E in a Patient with Type III Hyperlipoproteinemia > Discussion
What the sources say
- Not matchedcites Table IV
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
plain- Asserted: passes — The authors put it forward as true.
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In the paper
“This reagent adds a positive charge to cysteine residues and the resultant modified apo E has an altered pattern on isoelectric focusing (12).”
§ Apolipoprotein E2-Christchurch (136 Arg --Ser) New Variant of Human Apolipoprotein E in a Patient with Type III Hyperlipoproteinemia > Results
What the sources say
- Not checked — no full text of the sourcecites [12] 12. Weisgraber, K. H., S. C. Rall, Jr., and R. W. Mahley. 1981. Human E apoprotein heterogeneity. Cysteine-arginine interchanges in the amino acid sequence of the apo-E isoforms. J. Biol. Chem. 256: 9077-9083. source
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“As apo E3 is the most common form in the population (28, 45, 47), it is regarded as the parent (24) or normal isoform (48).”
§ Apolipoprotein E2-Christchurch (136 Arg --Ser) New Variant of Human Apolipoprotein E in a Patient with Type III Hyperlipoproteinemia > Results
What the sources say
- Not checked — no full text of the sourcecites [28] 28. Wardell, M. R., P. A. Suckling, and E. D. Janus. 1982. Genetic variation in human apolipoprotein E. J. Lipid Res. 23:1174-1182. source
- Not checked — no full text of the sourcecites [45] 45. Zannis, V. I., and J. L. Breslow. 1981. Human very low density lipoprotein apolipoprotein E isoprotein polymorphism is explained by genetic variation and posttranslational modification. Biochemistry. 20: 1033-1041. source
- Not checked — no full text of the sourcecites [47] 47. Utermann, G., M. Hees, and A. Steinmetz. 1977. Polymorphism of apolipoprotein E and occurrence of dysbetalipoproteinaemia in man. Nature (Lond.). 269:604-607. source
- Not checked — no full text of the sourcecites [24] 24. Innerarity, T. L., K. H. Weisgraber, K. S. Arnold, S. C. Rall, Jr., and R. W. Mahley. 1984. Normalization of receptor binding of apoli- poprotein E2. Evidence for modulation of the binding site conformation. J.Biol. Chem. 259:7261-7267. source
- Not checked — no full text of the sourcecites [48] 48. Gregg, R. E., L. A. Zech, E. J. Schaefer, and H. B. Brewer, Jr. 1984. Apolipoprotein E metabolism in normalipoproteinaemic human subjects. J. Lipid Res. 25:1167-1176. source
plain- Asserted: passes — The authors put it forward as true.
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In the paper
“The complex isoelectric focusing pattern exhibited by apo E results from posttranslational desialylation superimposed on genetic polymorphism (45,46).”
§ Apolipoprotein E2-Christchurch (136 Arg --Ser) New Variant of Human Apolipoprotein E in a Patient with Type III Hyperlipoproteinemia > Results
What the sources say
- Not checked — no full text of the sourcecites [45] 45. Zannis, V. I., and J. L. Breslow. 1981. Human very low density lipoprotein apolipoprotein E isoprotein polymorphism is explained by genetic variation and posttranslational modification. Biochemistry. 20: 1033-1041. source
- Not checked yetcites [46] 46. Zannis, V. I., P. W. Just, and J. L. Breslow. 1981. Human apo- lipoprotein E isoprotein subclasses are genetically determined. Am. J. Hum. Genet. 33:11-24.
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“The positively charged arginyl residue at position 158 is thought to maintain the correct conformation of the receptor-binding domain (24).”
§ Apolipoprotein E2-Christchurch (136 Arg --Ser) New Variant of Human Apolipoprotein E in a Patient with Type III Hyperlipoproteinemia > Introduction
What the sources say
- Not checked — no full text of the sourcecites [24] 24. Innerarity, T. L., K. H. Weisgraber, K. S. Arnold, S. C. Rall, Jr., and R. W. Mahley. 1984. Normalization of receptor binding of apoli- poprotein E2. Evidence for modulation of the binding site conformation. J.Biol. Chem. 259:7261-7267. source
hedgedconditional- Asserted: passes — The authors put it forward as true.
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In the paper
“The resultant loss of peptide T16 (Val-Arg) was not noted on peptide mapping because ofthe heterozygosity and because the sequence Arg-Val-Arg recurs further along the molecule.”
§ Apolipoprotein E2-Christchurch (136 Arg --Ser) New Variant of Human Apolipoprotein E in a Patient with Type III Hyperlipoproteinemia > Results
plaindirectSingle case- Asserted: passes — The authors put it forward as true.
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In the paper
“The new 136 Arg Ser substitution is consistent with the apo E-2/2 phenotype, with the cysteamine modification experiments and alterations in peptide mobility observed on mapping.”
§ Apolipoprotein E2-Christchurch (136 Arg --Ser) New Variant of Human Apolipoprotein E in a Patient with Type III Hyperlipoproteinemia > Discussion
plaincorrelationalSingle case- Asserted: passes — The authors put it forward as true.
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In the paper
“Apo E binds to two distinct high-affinity receptors mediating internalization and catabolism oflipoprotein particles.”
§ Apolipoprotein E2-Christchurch (136 Arg --Ser) New Variant of Human Apolipoprotein E in a Patient with Type III Hyperlipoproteinemia > Introduction
plaindirect- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“The positively charged amino acids in this region form ionic bonds with negatively charged residues in the consensus se- quence, which is repeated seven times in the ligand-binding region ofthe apo B,E (LDL) receptor (23).”
§ Apolipoprotein E2-Christchurch (136 Arg --Ser) New Variant of Human Apolipoprotein E in a Patient with Type III Hyperlipoproteinemia > Introduction
What the sources say
- Not checked — no full text of the sourcecites [23] 23. Yamamoto, T., C. G. Davis, M. S. Brown, W. J. Schneider, M. L. Casey, J. L. Goldstein, and D. W. Russell. 1984. The human LDL receptor: a cysteine-rich protein with multiple Alu sequences in its mRNA. Cell. 39:27-38. source
plaindirect- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim.
In the paper
“The second is the apo E or remnant receptor, which is found in hepatic tissues only and is able to recognize particles containing apo E but not apo B (18).”
§ Apolipoprotein E2-Christchurch (136 Arg --Ser) New Variant of Human Apolipoprotein E in a Patient with Type III Hyperlipoproteinemia > Introduction
What the sources say
- Not checked — no full text of the sourcecites [18] 18. Hui, D. Y., T. L. Innerarity, and R. W. Mahley. 1981. Lipoprotein binding to canine hepatic membranes. Metabolically distinct apo-E and apo-B,E receptors. J. Biol. Chem. 256:5646-5655. source
plain- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Type III is currently believed to result from two gene defects, one in the apo E structural gene and the other in a gene causing hyperlipidemia, probably familial combined hyperlipidemia (2, 11).”
§ Apolipoprotein E2-Christchurch (136 Arg --Ser) New Variant of Human Apolipoprotein E in a Patient with Type III Hyperlipoproteinemia > Introduction
What the sources say
- Not matchedcites [2] 2. Utermann, G., N. Pruin, and A. Steinmetz. 1979. Polymorphism of apolipoprotein E. III. Effect of a single polymorphic gene locus on plasma lipid levels in man. Clin. Genet. 15:63-72.
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- Not checked — no full text of the sourcecites [11] 11. Hazzard, W. R., G. R. Warnick, G. Utermann, and J. J. Albers. 1981. Genetic transmission of isoapolipoprotein E phenotypes in a large kindred: relationship to dyslipoproteinaemia and hyperlipidaemia. Me- tabolism. 30:79-88. source
hedgeddirect- Asserted: passes — The authors put it forward as true.
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- Not matched
A claim is checked only against the cited paper’s full text, never its abstract, and none is available for its sources.
In the paper
“Secondary structure predictions (54,55) suggest that position 136 is part of an a-helix that extends between residues 130 and 150 (13,24), encompassing the receptor-binding domain from 140 to 150 (22).”
§ Apolipoprotein E2-Christchurch (136 Arg --Ser) New Variant of Human Apolipoprotein E in a Patient with Type III Hyperlipoproteinemia > Discussion
What the sources say
- Not checked — no full text of the sourcecites [54] 54. Chou, P. Y., and G. D. Fasman. 1974. Conformational parameters for amino acids in helical, 3-sheet, and random coil regions calculated from proteins. Biochemistry. 13:211-222. source
- Not checked — no full text of the sourcecites [55] 55. Chou, P. Y., and G. D. Fasman. 1974. Prediction of protein conformation. Biochemistry. 13:222-245. source
- Not checked — no full text of the sourcecites [13] 13. Rall, S. C., Jr., K. H. Weisgraber, and R. W. Mahley. 1982. Human apolipoprotein E. The complete amino acid sequence. J. Biol. Chem. 257:4171-4178. source
- Not checked — no full text of the sourcecites [24] 24. Innerarity, T. L., K. H. Weisgraber, K. S. Arnold, S. C. Rall, Jr., and R. W. Mahley. 1984. Normalization of receptor binding of apoli- poprotein E2. Evidence for modulation of the binding site conformation. J.Biol. Chem. 259:7261-7267. source
- Not checked — no full text of the sourcecites [22] 22. Weisgraber, K. H., T. L. Innerarity, K. J. Harder, R. W. Mahley, R. W. Milne, Y. L. Marcel, and J. T. Sparrow. 1983. The receptor- binding domain of human apolipoprotein E. Monoclonal antibody in- hibition of binding. J. Biol. Chem. 258:12348-12354. source
hedged- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“A possible explanation for the different apo E2 isoform ratios found in the father and daughter is that one normal allele gives enough functional apo E to clear particles, whereas when both alleles are abnormal, another slower mechanism exists for the removal ofthese particles, thus allowing for the build-up oftheir remnants.”
§ Apolipoprotein E2-Christchurch (136 Arg --Ser) New Variant of Human Apolipoprotein E in a Patient with Type III Hyperlipoproteinemia > Discussion
hedgedconditionalSingle case- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
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It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The longer circulatory time of the remnants may be associated with different exchange rates of the two apo E2 iso- forms with other lipoprotein classes, or apo E2 (136 Arg --Ser) may have a slower catabolic rate than apo E2 (158 Arg -.Cys).”
§ Apolipoprotein E2-Christchurch (136 Arg --Ser) New Variant of Human Apolipoprotein E in a Patient with Type III Hyperlipoproteinemia > Discussion
hedgedconditionalSingle case- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
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Probably not a substantial claim. It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Of some 300 characterized point mutations in hemoglobin (56), none result in increased expression, though missplicing of a pseudo-intron in hemoglobin E ((#26 Glu -.Lys) results in decreased expression (57).”
§ Apolipoprotein E2-Christchurch (136 Arg --Ser) New Variant of Human Apolipoprotein E in a Patient with Type III Hyperlipoproteinemia > Discussion
What the sources say
- Not checked yetcites [56] 56. International Hemoglobin Information Center Variant List. 1985. Hemoglobin. 9:229-298.
- Not checked — no full text of the sourcecites [57] 57. Orkin, S. H., H. H. Kazazian, Jr., S. E. Antonarakis, H. Ostrer, S. C. Goff, and J. P. Sexton. 1982. Abnormal RNA processing due to the exon mutation of (#E-globin gene. Nature (Lond.). 300:768-769. source
plain- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
In the paper
“In this way, a substitution at position 136 could alter receptor binding, as happens in the case of apo E2 (158 Arg -* Cys) (24), which also lies outside the recognized receptor-binding domain.”
§ Apolipoprotein E2-Christchurch (136 Arg --Ser) New Variant of Human Apolipoprotein E in a Patient with Type III Hyperlipoproteinemia > Discussion
What the sources say
- Not checked — no full text of the sourcecites [24] 24. Innerarity, T. L., K. H. Weisgraber, K. S. Arnold, S. C. Rall, Jr., and R. W. Mahley. 1984. Normalization of receptor binding of apoli- poprotein E2. Evidence for modulation of the binding site conformation. J.Biol. Chem. 259:7261-7267. source
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
The paper relies on this without support.
The apo E2 variant by itself is not sufficient to cause type III hyperlipoproteinemia; only about 2% of apo E2 homozygotes have the disease.
“The variant apo E2 alone is not sufficient to cause type III, however, as only -2% of all apo E2 homozygotes have this disease.”
The paper relies on this without support.
There are only two histidine-containing peptides in apo E, T17 and T39.
“As there are only two histidine-containing peptides in apo E (T17 and T39), one of these peptides must be implicated, or the mutation has introduced a new histidine.”
The paper relies on this without support.
The relative amount of apo E2(136 Arg->Ser) versus apo E2(158 Arg->Cys) in VLDL reflects the mutant's contribution to the patient's hyperlipidemia.
“His very low-density lipoprotein contained approximately five times more apo E2 (136 Arg -Ser) than apo E2 (158 Arg --Cys), as determined by cysteamine treatment and peptide mapping.This new apo E2 mutant thus appears to contribute significantly to the patient's hyperlipidemia.”
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?
The cited source doesn’t support the claim as written.
In the citing paper
“She had two copies of the APOE3 Christchurch (R136S) mutation, unusually high brain amyloid, and limited tau/tangle and neurodegenerative measurements.”
From Resistance to autosomal dominant Alzheimer’s disease in an APOE3 Christchurch homozygote: a case report (2019) · cites this paper as [7]
Checked by a reasoning model — may be wrong.
Experimental — accuracy not yet measuredThe cited source doesn’t support the claim as written.
In the citing paper
“Notably, the APOE-R136S has severely reduced binding affinity to heparin, as the mutation occurs within the receptor-binding region of APOE36,45,58.”
From The APOE-R136S mutation protects against APOE4-driven tau pathology, neurodegeneration, and neuroinflammation (2023) · cites this paper as [45]
Checked by a reasoning model — may be wrong.
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“A major functional effect of the R136S mutation is disruption of its binding to anionic HSPGs on cell surface36,45.”
From The APOE-R136S mutation protects against APOE4-driven tau pathology, neurodegeneration, and neuroinflammation (2023) · cites this paper as [45]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“by substituting a positively charged arginine residue for the uncharged serine, the affinity of the receptor-binding domain of APOE-R136S for negatively charged HSPGs is greatly diminished36,45,58”
From The APOE-R136S mutation protects against APOE4-driven tau pathology, neurodegeneration, and neuroinflammation (2023) · cites this paper as [45]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Specifically, heterozygosity for the apoE variant apoE3[R136S] (previously designated apoE2 Christchurch) with the apoE2 allele results in type III HLP [27].”
From Biophysical Analysis of Apolipoprotein E3 Variants Linked with Development of Type III Hyperlipoproteinemia (2011) · cites this paper as [27]
Experimental — accuracy not yet measured
The source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“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 [47]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“In contrast, certain other apoE variants are associated with a dominant mode of inheritance (5-10), i.e., heterozygosity for these apoE variants is sufficient for the expression of type III hlp.”
From Preferential association of apolipoprotein E Leiden with very low density lipoproteins of human plasma. (1993) · cites this paper as [7]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Rare APOE variants associated with dominant type III HLPs include single-nucleotide substitutions at APOE2 Heidelberg (Arg136Cys)47), APOE2 Christchurch (Arg136Ser)26, 48), APOE2 (Arg142Cys)49, 50), APOE2 (Arg142Leu)51), APOE2 (Lys146Gln)45), and APOE1 Harrisburg (Lys146Glu)52, 53) (Table 2, Fig.5).”
From Impact of Apolipoprotein E Variants: A Review of Naturally Occurring Variants and Clinical Features (2025) · cites this paper as [48]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“The Christchurch variant rs121918393 (APOEChc: CGC > aGC, p.Arg[R]136Ser[S]) [19–21] and the Jacksonville variant rs199768005 (APOEJax: GTG > GaG, p.Val[V]236Glu[E]) [22, 23] have been identified as protective variants against AD in Caucasians”
From Genetics of Alzheimer’s disease: An East Asian perspective (2023) · cites this paper as [19]
Experimental — accuracy not yet measuredThe cited source says what the claim attributes to it.
In the citing paper
“Whole exome sequencing corroborated her PSEN1 E280A mutation and discovered that she had two copies of the rare Christchurch (APOEch)7 mutation (an arginine-to-serine substitution at amino acid 136, corresponding to codon 154) in APOE3.”
From Resistance to autosomal dominant Alzheimer’s disease in an APOE3 Christchurch homozygote: a case report (2019) · cites this paper as [7]
The cited source says what the claim attributes to it.
In the citing paper
“APOE R136S is a very rare mutation (0.0004% allele frequency in the European population37) that was originally described in APOEε2 alleles of people with type III hyperlipoproteinaemia38,39, but is much more common in APOEε3 homozygotes than in any other genotype and has also been associated with increased plasma apolipoprotein B (APOB) levels37.”
From Multifaceted roles of APOE in Alzheimer disease (2024) · cites this paper as [38]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
Each contradiction between two passages listed here was confirmed by an independent check.
Rated minor: it would not touch a result — a value no result rests on, a p-value that stays on the same side of the significance level, or a conflict that is clerical, resolved elsewhere in the paper, or outside its own findings.
In the paper
§ Apolipoprotein E2-Christchurch (136 Arg --Ser) New Variant of Human Apolipoprotein E in a Patient with Type III Hyperlipoproteinemia > Results
“All were undergoing dietary and clofibrate treatment that had successfully lowered their plasma cholesterol and triglyceride levels to normal values (Table I).”
§ Apolipoprotein E2-Christchurch (136 Arg --Ser) New Variant of Human Apolipoprotein E in a Patient with Type III Hyperlipoproteinemia > Results
“J.S.F. 30 M 194 84.5 E-2/2 9.5 15.8 6.9 6.6”
Citations
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Cited by
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Apolipoprotein E: Cholesterol Transport Protein with Expanding Role in Cell Biology
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The Amyloid-β Pathway in Alzheimer’s Disease
Hampel, H., Hardy, J., Blennow, K., Chen, C., Perry, G., Kim, S. H., Villemagne, V. L., Aisen, P., Vendruscolo, M., Iwatsubo, T., et al. (2021) · Molecular Psychiatry · doi:10.1038/s41380-021-01249-0 · Cited by 1,952
Apolipoprotein E: Structure-Function Relationships
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ApoE in Alzheimer’s disease: pathophysiology and therapeutic strategies
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“APOE3-Ch was discovered in 1987 as a susceptibility factor for type III hyperlipoproteinemia in Caucasian populations [180].”
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“A major functional effect of the R136S mutation is disruption of its binding to anionic HSPGs on cell surface 36,45 .”
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“This specific incidence of resilience was attributed to the presence of a homozygous APOE variant known as the Christchurch mutation [23] that confers reductions in low-density lipoprotein receptor and heparin binding [20], implicating these mechanisms as putative drivers of resilience in the face of high amyloid depo…”
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“15 The R136S Christchurch mutation is located in the domain involved in the interaction between ApoE and heparan sulfate proteoglycans (HSPG)andinthebindingtothelow-densitylipoprotein(LDL)andLDL receptor-related protein (LRP) receptors.”
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“The Christchurch mutation results in a Arg136Ser substitution [18].”
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“Mutations in apoE that prevent its binding to the low-density lipoprotein (LDL) receptor and possibly other receptors are associated with type III hyperlipoproteinemia and premature atherosclerosis (6-14).”
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“Using the isoelectric focusing techniques [45] at least four different bands (corresponding to different ApoE2 conformational status) have been identified: E2 (arg158to-cys) [46], E2 (lys146-to-gln) [47], E2 (arg145-to-cys), and E2-Christchurch (arg136-to-ser) [48].”
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“This protection was evidently afforded by a second germline mutation in the ApoE3 gene that disrupts lipid metabolism (7), highlighting the possibility that the pathogenic effects of A β may be dominantly inhibited by preexisting physiological processes upstream of A β .”
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“Multiple rare APOE coding risk variants have also been identified, including the APOE-e1 Weisgraber allele (Asp127–Cys158) [64], APOE-e1y (Arg112–Cys158) [65], several forms of APOE-e5 (including Lys3 and Arg84–Arg112) [66,67], APOE-e7 (Lys244–Lys245) [68], and the Christchurch mutation (R136S or Ser136) [69], which p…”
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“The R145C variant reduces the positive charge of this domain,(8,21) because it has 40% of the binding affinity of ApoE3 to the LDL receptor.(8,21) This discrepancy in disease manifestation might be explained by considering the role of other ApoE receptors in the clearance of remnant particles from the circulation, inc…”
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Identification of apolipoprotein E polymorphism by using synthetic oligonucleotides.
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“136, 140, 142, 143, 145, 150, and 158 of the human mature peptide)as crucial residues involved in receptor binding (Wardell et al. 1987; Lalazar et al. 1988).”
BackgroundAtherogenic Lipoproteins Resulting from Genetic Defects of Apolipoproteins B and E
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“88 In the UK biobank study with 455,306 participants, the frequency of APOEch is approximately 0.004%, where the variant is enriched in the APOE3/E3 genotype.”
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“biguously shown to be the domain responsible for apoE binding to the LDL receptor (6-10).”
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Human apolipoprotein E glycosylation and sialylation: from structure to function
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Metadata
- Authors
- Wardell, M. R., Brennan, S. O., Janus, E. D., Fraser, R., & Carrell, R. W.
- Affiliations
- Christchurch Hospital (NZ)
- Venue
- Journal of Clinical Investigation
- Published
- 1987-08-01
- Volume
- 80
- Issue
- 2
- Pages
- 483-490
- ISSN
- 0021-9738 (ISSN-L)
- PMC
- PMC442261
- OpenAlex
- W1978899417
- Cited by
- 159
- References
- 61
- Citations by year
- 2026: 6 · 2025: 4 · 2024: 9 · 2023: 6 · 2022: 10 · 2021: 6 · 2020: 4 · 2019: 3 · 2018: 1 · 2016: 4 · 2015: 2 · 2014: 1 · 2013: 1 · 2012: 2
- FWCI
- 16.95
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Clinical Investigation (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Heart Foundation of New Zealand
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Lipoproteins and Cardiovascular Health
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Lipid metabolism and disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Cholesterol and Lipid Metabolism
- Keywords
- apolipoprotein E, apolipoprotein E2, type III hyperlipoproteinemia, apolipoprotein E3, tryptic peptide mapping, VLDL, heterozygous mutation, hyperlipidemia
- MeSH terms
- Adult, Amino Acid Sequence, Apolipoproteins E, Female, Humans, Hyperlipoproteinemia Type III, Male, Middle Aged, Mutation, Pedigree, Peptide Mapping, Receptors, Cell Surface, Low Density Lipoprotein Receptor-Related Protein-1
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.
A language model drew the claims from the paper on 2026-10-01, under version 3 of the claim definition (model deepseek-v4.1-flash, prompt extract-v3).
A second model labelled each claim on 2026-10-01 (model jev-1.13-20260917, definition revision gold-guideline-v0.2).
Cited sources are checked with a language model’s help (gpt-6-sol).
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 ›
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