Abstract
The risk factors for atherosclerosis and coronary heart disease
(CHD) are multiple and may interact with each other. Diet has a
significant role among the main risk factors for atherosclerosis,
as it regulates the levels of plasma lipids and lipoproteins, their
oxidative modification or protection from oxidation, blood pressure,
energy balance, and thrombogenesis. Nutrients can transfer their
effects directly through plasma concentrations or modify the cell
transduction or gene expression of important regulatory genes. The
response to dietary modification varies between individuals. The plasma
cholesterol response induced by dietary modification is at least
partly regulated genetically and some of the variation is explained
by other environmental factors.
Apolipoprotein E (apo E) and apolipoprotein B (apo B) are
the key regulatory proteins in cholesterol and lipoprotein metabolism.
The genetic variation of apo E is associated with the plasma lipid
levels and the CHD risk. The polymorphic variation of the apo B
gene is also associated with increased plasma cholesterol and CHD
risk. Obesity is associated with increased morbidity and mortality.
Plasma lipid abnormalities, impaired glucose metabolism and increased
blood pressure caused by obesity are the main reasons for increased
CHD mortality among obese subjects.
To study the magnitude of the response to dietary modification,
genetically selected groups were investigated. Dietary modification
had a significant impact on plasma total, LDL, and HDL cholesterol
concentrations, and the individual response in plasma LDL cholesterol
varied from 3 to 100%. The role of genetic variation in
the apo E gene was not significant in the lipid response, but the
blood pressure response was more distinct among subjects with the ε 4
allele than those with the ε 3 allele. The determination
of apo B EcoRI and MspI gene polymorphisms revealed subjects with a
greater response to diet, a finding which may have clinical importance
in the future for the attempt to identify subjects for effective
dietary counselling.
The effect of caloric restriction on gene expression was studied
in obese gallstone patients. Moderate weight reduction during caloric
restriction was associated with reduced lipoprotein lipase gene
expression, while the cholesteryl ester transfer protein gene expression
remained unchanged. Some of the beneficial changes in plasma lipids
and lipoproteins during and after weight reduction may be followed
by altered transcription of their modifying genes.
Meta-analysis is a modern and generally accepted method. Many
clinical uncertainties can be solved by combining all the data available
to a quantitative and objective analysis. However, the use of meta-analysis
do not resolve the problem of the effect of publication bias.
| Identifer | oai:union.ndltd.org:oulo.fi/oai:oulu.fi:isbn951-42-5652-2 |
| Date | 08 May 2000 |
| Creators | Rantala, M. (Maire) |
| Publisher | University of Oulu |
| Source Sets | University of Oulu |
| Language | English |
| Detected Language | English |
| Type | info:eu-repo/semantics/doctoralThesis, info:eu-repo/semantics/publishedVersion |
| Format | application/pdf |
| Rights | info:eu-repo/semantics/openAccess, © University of Oulu, 2000 |
| Relation | info:eu-repo/semantics/altIdentifier/pissn/0355-3221, info:eu-repo/semantics/altIdentifier/eissn/1796-2234 |
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