University of Oulu

Effects of apolipoprotein and low density lipoprotein receptor gene polymorphisms on lipid metabolism, and the lipid risk factors of coronary artery disease

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Author: Korhonen, Taina1,2
Organizations: 1University of Oulu, Faculty of Medicine, Department of Internal Medicine
2University of Oulu, Biocenter Oulu
Format: ebook
Version: published version
Access: open
Online Access: PDF Full Text (PDF, 4.8 MB)
Persistent link: http://urn.fi/urn:isbn:9514251598
Language: English
Published: 1999
Publish Date: 1999-03-12
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 April 1st, 1999, at 12 noon.
Reviewer: Docent Timo Strandberg
Docent Hannu Vanhanen
Description:

Abstract

To facilitate the diagnosis of hypercholesterolemia, we wanted to create a simple and rapid method for diagnosing familial hypercholesterolemia in a homogenous population. The PCR method for the FH-Helsinki mutation detected 25 FH-Helsinki positive patients, two of whom had no clinical signs of FH, but had a positive family history for the disease. The method is exceptionally useful in Northern Finland, where 62% of the FH patients carry the FH-Helsinki mutation.

The role of polymorphisms and mutations of the apo B particle as etiologic factors of hypercholesterolemia was studied in a population of moderately hypercholesterolemic individuals. The catabolism of the patients' own LDL was compared to that of a healthy and normocholesterolemic donor, and no major differences were observed. However, the presence of the XbaI cutting site was associated with elevated cholesterol values and a slightly lowered LDL catabolic rate. Patients homozygous for the EcoRI cutting site also had a slow LDL catabolic rate and slightly elevated cholesterol values. The MspI and Ins/del polymorphisms of the apo B particle were not associated with variations in LDL catabolism.

The e 4 allele of apolipoprotein E was slightly more frequent in our hypercholesterolemic population than in the average population. The lipid values did not differ significantly between the apo E phenotypes in moderately hypercholesterolemic individuals, nor could we detect any differences in the catabolic rates of their LDL according to the apo E phenotype (individuals with the phenotype apo E 2/2 were excluded from the study). In our population of CAD patients, the frequency of the e 4 allele was lower than in CAD populations from Southern Finland (0.23 vs. 0.32), suggesting that apo E 4 is not so strongly associated with coronary disease in Northern Finland as in other populations. The E 4 phenotype was associated with slightly smaller LDL cholesterol reductions by colestipol and lovastatin treatment compared with patients with the phenotype 2/3.

The lipid risk factors of male and female CAD patients were studied in a group of patients admitted to one ward of the Oulu University Hospital. We found the males to have the typical high LDL cholesterol and low HDL cholesterol lipid pattern, but women with two- or three-vessel CAD had high LDL and low HDL cholesterol associated with high VLDL lipids, and hypertension, diabetes or smoking.

Pharmacological treatment of hypercholesterolemia was studied by comparing lovastatin to colestipol, and in a separate study where a new drug, enprostil was used. Enprostil, whose main effect is on the gastrointestinal tract, would be a useful alternative for long-term treatment of hypercholesterolemia. Unfortunately, however, gastrointestinal side-effects limit its long-term use. Colestipol reduced plasma LDL cholesterol and elevated plasma HDL cholesterol and triglycerides, but it, too, caused gastrointestinal side-effects. Lovastatin proved to be the most effective cholesterol-lowering drug with the least side-effects, and statins have now been established as the most widely used hypocholesterolemic drugs.

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Series: Acta Universitatis Ouluensis. D, Medica
ISSN-E: 1796-2234
ISBN: 951-42-5159-8
ISBN Print: 951-42-5173-3
Issue: 513
Subjects:
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