Use this URL to cite or link to this record in EThOS: https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.796303
Title: Genetic determinants of apolipoprotein B metabolism
Author: Demant, Thomas
Awarding Body: University of Glasgow
Current Institution: University of Glasgow
Date of Award: 1989
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Abstract:
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.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.796303  DOI: Not available
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