Dietary modification and genetic variability of atherosclerosis risk factors
1University of Oulu, Faculty of Medicine, Department of Internal Medicine
|Online Access:||PDF Full Text (PDF, 1.1 MB)|
|Persistent link:|| http://urn.fi/urn:isbn:9514256522
|Publish Date:|| 2000-05-08
|Thesis type:||Doctoral Dissertation
|Defence Note:||Academic Dissertation to be presented with the assent of the Faculty of Medicine, University of Oulu, for public discussion in Auditorium 10 of the University Hospital of Oulu, on May 31th, 2000, at 10 a.m.
Professor Markku Laakso
Professor Matti Uusitupa
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.
Acta Universitatis Ouluensis. D, Medica
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