Genetic abnormalities in apolipoprotein B

Young, Stephen G.; Linton, MacRae F.

doi:10.1016/1050-1738(91)90011-3

Cited by 11 publications

(3 citation statements)

References 39 publications

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“…Two components were resolved: one that appears to correspond to normal apoB-48 and one that is slightly larger. The larger component was not found in normal subjects, suggesting that it is an abnormal truncated form of apoB similar to those that are responsible for hypobetalipoproteinemia (12,13). The two components could not be separated by preparative SDS-PAGE and it was therefore necessary to perform subsequent protein analysis without further separation.…”

Section: Resultsmentioning

confidence: 97%

“…The very low levels ofapoB-50-containing LDL observed in the patient's plasma and the observation that virtually no label is found in the LDL interval after reinfusion of radiolabeled d < 1.006 g/ml lipoprotein suggest that either very little of the abnormal VLDL is processed to LDL or that the lipoproteins formed are removed at a very rapid rate. The absence ofthe putative LDLreceptor ligand domain from the LDL particles containing the apoB-50 protein would be expected to decrease substantially their removal by the LDL receptor and cause their accumulation in plasma (12). Thus, the low levels of LDL present most likely reflect removal of apoB-50 VLDL particles before they can be converted to LDL.…”

Section: Discussionmentioning

confidence: 99%

“…Analysis ofthe protein by an electrophoretic gel technique of high resolution then revealed a finely spaced doublet. Several truncations of apoB-100 have now been described in patients with familial hypobetalipoproteinemia (12,13), all due to mutations producing inappropriate stop codons. We have found a unique mutation in the genomic DNA from our patient, which results in production ofan apoB-50 protein.…”

Section: Introductionmentioning

confidence: 99%

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Molecular and metabolic basis for the metabolic disorder normotriglyceridemic abetalipoproteinemia.

Hardman¹,

Pullinger²,

Hamilton³

et al. 1991

J. Clin. Invest.

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We have previously described a disorder, normotriglyceridemic abetalipoproteinemia, that is characterized by the virtual absence of plasma low density lipoproteins and complete absence of apoB-100, but with apparently normal secretion of triglyceride-rich lipoproteins containing apoB48. The patient's plasma lipoproteins were shown on polyacrylamide gels and by antibody mapping to have a new truncated apoB variant, apoB-50, circulating along with her apoB-48. We have found this individual to be homozygous for a single C-to-T nucleotide substitution at apoB codon 2252, which produces a premature in-frame stop codon. Thus, this is a rare example of homozygous hypobetalipoproteinemia. Electron photomicrographs revealed that the diameters of particles in the d < 1.006 g/ml lipoprotein fraction, in both the postprandial and postabsorptive state, are bimodally distributed. The molar ratio of apoE to apoB in these particles is 3.5:1, similar to normal VLDL. The plasma LDL interval contains both spherical and cuboidal particles. Autologous reinfusion of labeled d < 1.006 g/ml lipoproteins showed exponential disappearance from plasma, with an apparent halfremoval time of 50 min, somewhat slower than for normal chylomicrons but within the normal range for VLDL. The calculated production rate for apo B was within the normal range in this subject. A very small amount of label was found briefly in the IDL fraction, but none at any time in LDL or HDL. Therefore, because LDL particles that contain apoB-50 lack the putative ligand domain of the LDL receptor, we conclude that the very low level of LDL is due to the rapid removal of the abnormal VLDL particles before their conversion to LDL can take place. (J. Clin. Invest. 1991. 88:1722-1729

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Section: Resultsmentioning

confidence: 97%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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