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UBC Theses and Dissertations
Interactive influence of apolipoprotein e genotype and dietary cholesterol on cholesterol synthesis in humans Main , Blair F.
Abstract
Apolipoprotein (apo) E is a 299 amino acid polypeptide that mediates the uptake of apo E containing lipoproteins by receptor-mediated endocytosis. Allelic differences at the apo E gene locus are responsible for as much as 8% of the variance of low density lipoprotein (LDL) cholesterol. Due to the association between LDL cholesterol levels and atherosclerosis, it has been suggested that apo E polymorphism may play a role in determining the risk of coronary artery disease. A method for apo E genotyping was developed using the polymerase chain reaction (PCR) with allele-specific oligonucleotide primers. The fourteen phenotypes identified by isoelectric focusing methods were consistent with the fourteen genotypes identified by the PCR method. Seven E2/- and six E4/- volunteers were selected for a dietary study investigating the interactive effects of apo E polymorphism and dietary cholesterol levels on cholesterol synthesis rates. Volunteers underwent two dietary treatments consisting of a low cholesterol diet (250 mg/day) and a high cholesterol diet (800 mg/day). At the end of each diet period an oral dose of deuterium was given at 0.7 g/Kg body water to determine fractional synthetic rate (FSR) of cholesterol. The apo E4/- group had a significantly higher serum total cholesterol level than the E2/- group throughout both dietary treatments. Cholesterol FSR was not significantly different between apo E groups when comparing dietary cholesterol levels. The apo E4/- did respond to fasting state differently from the E2/- group by not depressing cholesterol synthesis while on a low cholesterol diet. This suggests E4/- individuals may not have a sensitive endogenous feedback mechanism to suppress cholesterol synthesis while on a low cholesterol diet.
Item Metadata
Title |
Interactive influence of apolipoprotein e genotype and dietary cholesterol on cholesterol synthesis in humans
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Creator | |
Publisher |
University of British Columbia
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Date Issued |
1992
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Description |
Apolipoprotein (apo) E is a 299 amino acid polypeptide that mediates the uptake of apo E containing lipoproteins by receptor-mediated endocytosis. Allelic differences at the apo E gene locus are responsible for as much as 8% of the variance of low density lipoprotein (LDL) cholesterol. Due to the association between LDL cholesterol levels and atherosclerosis, it has been suggested that apo E polymorphism may play a role in determining the risk of coronary artery disease. A method for apo E genotyping was developed using the polymerase chain reaction (PCR) with allele-specific oligonucleotide primers. The fourteen phenotypes identified by isoelectric focusing methods were consistent with the fourteen genotypes identified by the PCR method. Seven E2/- and six E4/- volunteers were selected for a dietary study investigating the interactive effects of apo E polymorphism and dietary cholesterol levels on cholesterol synthesis rates. Volunteers underwent two dietary treatments consisting of a low cholesterol diet (250 mg/day) and a high cholesterol diet (800 mg/day). At the end of each diet period an oral dose of deuterium was given at 0.7 g/Kg body water to determine fractional synthetic rate (FSR) of cholesterol. The apo E4/- group had a significantly higher serum total cholesterol level than the E2/- group throughout both dietary treatments. Cholesterol FSR was not significantly different between apo E groups when comparing dietary cholesterol levels. The apo E4/- did respond to fasting state differently from the E2/- group by not depressing cholesterol synthesis while on a low cholesterol diet. This suggests E4/- individuals may not have a sensitive endogenous feedback mechanism to suppress cholesterol synthesis while on a low cholesterol diet.
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Extent |
3660997 bytes
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Genre | |
Type | |
File Format |
application/pdf
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Language |
eng
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Date Available |
2008-09-17
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Provider |
Vancouver : University of British Columbia Library
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Rights |
For non-commercial purposes only, such as research, private study and education. Additional conditions apply, see Terms of Use https://open.library.ubc.ca/terms_of_use.
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DOI |
10.14288/1.0086452
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URI | |
Degree | |
Program | |
Affiliation | |
Degree Grantor |
University of British Columbia
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Graduation Date |
1992-05
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Campus | |
Scholarly Level |
Graduate
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Aggregated Source Repository |
DSpace
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Item Media
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Rights
For non-commercial purposes only, such as research, private study and education. Additional conditions apply, see Terms of Use https://open.library.ubc.ca/terms_of_use.