Genetic Determinants of Apolipoprotein B Metabolism

Demant, Thomas (1989) Genetic Determinants of Apolipoprotein B Metabolism. PhD thesis, University of Glasgow.

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In this thesis the influence of genetic factors on the apolipoprotein B metabolism in humans was investigated. The phenotype of the apolipoprotein E polymorphism was determined for normolipidaemic subjects (n = 1600). The metabolism of apolipoprotein B in fifteen subjects, homozygous for apoE3, apoE4 or apoE2, was examined by VLDL-turnover studies, using trace-labelled VLDL1 (Sf 60-400) and VLDL2 (Sf 20-60). Results were used for computer modelling of the apoB metabolism, which enabled quantitative comparisons between the three study groups. In apoE2/2 subjects, clearance of VLDL1 and VLDL2 as well as transfer from IDL into LDL was found to be delayed and in apoE4/4 subjects the LDL-FCR was reduced as compared to apoE3/3 normolipidaemics. These observations explain the correlation between apoE phenotypes and plasma cholesterol levels, which had been observed previously by others and were confirmed in the present study. The Xbal restriction site polymorphism of the apoB gene was analysed in nineteen hypercholesterolaemic patients and correlated with fractional catabolic rates for LDL as defined by LDL-turnover studies. The X2 allele was found to be linked with a decreased LDL-FCR, in line with previous reports of a correlation between X2X2 genotype and increased plasma cholesterol concentrations. In addition to these studies of common genetic determinants of apoB metabolism, five patients with rare inherited disorders of lipoprotein metabolism were investigated. These conditions were homozygous familial hypercholesterolaemia, lipoprotein lipase deficiency and hepatic lipase deficiency. VLDL-turnovers in these subjects revealed the significance of the LDL-receptor and the two lipolytic enzymes for apolipoprotein B metabolism. Finally, some conclusions were drawn about metabolic heterogeneity within the VLDL subfraction and about apoB synthesis.

Item Type: Thesis (PhD)
Qualification Level: Doctoral
Keywords: Genetics
Date of Award: 1989
Depositing User: Enlighten Team
Unique ID: glathesis:1989-78118
Copyright: Copyright of this thesis is held by the author.
Date Deposited: 28 Feb 2020 12:09
Last Modified: 28 Feb 2020 12:09

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