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Frequency of selected genetic polymorphisms of cytochrome P450 in the Czech population and the influence of CYP2C9 genotype on the hypolipidemic effect of fluvastatin
Buzková, Helena ; Perlík, František (advisor) ; Bultas, Jan (referee) ; Mičuda, Stanislav (referee)
55 Abstract Frequency of selected genetic polymorphisms of cytochrome P450 in the Czech population and the influence of CYP2C9 genotype on the hypolipidemic effect of fluvastatin Introduction: One of the main factors of genetically determined variability in response of humans to administered drugs are differences in catalytic activity of metabolizing enzymes, which are caused mainly by genetic polymorphisms in cytochrom P450 family enzymes. This thesis consists of two parts and it is presented as a commentary to the original papers. The first aim was to investigate the frequency of functionally important variant alleles of three main isoenzymes of cytochrome P450 gene: CYP2D6, CYP2C9, CYP2C19, throughout the Czech population, predict the prevalence of poor metabolizer phenotypes, and then to compare the results to the data from other populations. Secondly, we analysed the correlation between the CYP2C9 genotype and cholesterol-lowering effect of fluvastatin in human hypercholesterolemic patients. Methods: Genotypes were determined by PCR-RFLP. The presence of alleles CYP2D6*1, *6, *5, *4, *3, and gene duplication was analysed in 233 healthy volunteers, CYP2C9*1, *2 and*3 in 254 subjects and CYP2C19*1, *2 and *2 in 218 subjects. Eighty seven patients on fluvastatin therapy, and 48 patients on monotherapy...
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Alimentation of hypercholesterolemic patients
VALENTOVÁ, Lucie
The Bachelor thesis is focused on eating of patients suffering from hypercholesterolemia. The main goal of Bachelor thesis was to find out how patients with hypercholesterolemia eat and what impact to the cholesterol level does the change of eating habits have. The thesis is divided into theoretical and practical part. The theoretical part describes the basic food ingredients, cholesterol and characteristics of hypercholesterolemia, its types, risk factors influencing its development, treatment options and prevention of the illness. It deals with the influence of individual food ingredients to cholesterol level and diet measures to decrease cholesterol level in blood. In conclusion the theoretical part describes atherosclerosis, which is closely related to hypercholesterolemia. The practical part was created by a qualitative research using semi-structured interviews. Interviews were lead with six patients suffering from hypercholesterolemia with high concentration of cholesterol in blood. Then the patients were instructed to record their menus for one week. I entered these menus into "Nutriservis Professional" program, which helped me evaluate them and thanks to this I was able to determine the average cholesterol intake in a patient's diet. Then I gave the patients a diet recommendation they should follow for the next six months. After this period, patients were asked to check their cholesterol level again, which helped me to find out the influence of the diet to level of cholesterol. It can be seen from the results of the research that in case the diet is kept, and a physical activity is included into a normal life, the patients can successfully decrease cholesterol level in blood. We can notice that most patients exceeded the recommended 300mg daily dose of cholesterol. The Bachelor thesis can serve as a teaching material for patients suffering from hypercholesterolemia, but it can also serve to increase knowledge about this disease.
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Genetic determination of cholesterolemia regulation
Vlachová, Miluše ; Kovář, Jan (advisor) ; Vrablík, Michal (referee) ; Kazdová, Ludmila (referee)
Most types of hypercholesterolemia are of polygenic origin. Some genes related to hypercholesterolemia are known, although all genes responsible for cholesterolemia regulation have not been characterised yet. To identify these new genes, animal models with spontaneous defects in cholesterol metabolism could be very useful. Moreover, a number of variations and polymorphisms have been found to influence blood cholesterol levels in humans. Some may also affect cholesterolemia responsiveness to dietary fat. The Prague hereditary hypercholesterolemic (PHHC) rat is a unique model of hypercholesterolemia induced by dietary cholesterol alone (without administration of cholic acid or thyrotoxic drugs). It exhibits modestly increased cholesterolemia when fed chow and responds to a diet containing cholesterol with a several-fold increase of cholesterolemia to concentrations comparable to those observed in hypercholesterolemic patients. Hypercholesterolemia in this model is characterised by accumulation of very low density lipoproteins (VLDL) and intermediate density lipoproteins (IDL) enriched by cholesterol. In an experiment with tyloxapol (an inhibitor of lipoprotein lipase) we found that PHHC rats on a cholesterol diet incorporated twice as much cholesterol into VLDL as Wistar rats, although liver...
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Frequency of selected genetic polymorphisms of cytochrome P450 in the Czech population and the influence of CYP2C9 genotype on the hypolipidemic effect of fluvastatin
Buzková, Helena ; Perlík, František (advisor) ; Bultas, Jan (referee) ; Mičuda, Stanislav (referee)
55 Abstract Frequency of selected genetic polymorphisms of cytochrome P450 in the Czech population and the influence of CYP2C9 genotype on the hypolipidemic effect of fluvastatin Introduction: One of the main factors of genetically determined variability in response of humans to administered drugs are differences in catalytic activity of metabolizing enzymes, which are caused mainly by genetic polymorphisms in cytochrom P450 family enzymes. This thesis consists of two parts and it is presented as a commentary to the original papers. The first aim was to investigate the frequency of functionally important variant alleles of three main isoenzymes of cytochrome P450 gene: CYP2D6, CYP2C9, CYP2C19, throughout the Czech population, predict the prevalence of poor metabolizer phenotypes, and then to compare the results to the data from other populations. Secondly, we analysed the correlation between the CYP2C9 genotype and cholesterol-lowering effect of fluvastatin in human hypercholesterolemic patients. Methods: Genotypes were determined by PCR-RFLP. The presence of alleles CYP2D6*1, *6, *5, *4, *3, and gene duplication was analysed in 233 healthy volunteers, CYP2C9*1, *2 and*3 in 254 subjects and CYP2C19*1, *2 and *2 in 218 subjects. Eighty seven patients on fluvastatin therapy, and 48 patients on monotherapy...
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Pathogenesis of hypercholesterolemia in Prague hereditary hypercholesterolemic (PHHC) rat
Rybáková, Kateřina ; Vlachová, Miluše (advisor) ; Poledne, Rudolf (referee)
Hypercholesterolemia represents a major risk factor of cardiovascular disease. A number of experimental models is used for study of hypercholesterolemia pathogenesis and therapy. This thesis concentrates on characterization of one of these models. Prague hereditary hypercholesterolemic (PHHC) rat is such a suitable model for study of hypercholesterolemia. Although the majority of plasma cholesterol is transported by high density lipoprotein in PHHC rat fed standard diet, PHHC rat fed cholesterol diet develops hypercholesterolemia comparable to that of humans. The advantage of this model is that hypercholesterolemia develops without the need for addition of bile acids or other hepatotoxic substances to the diet. The hypercholesterolemia of PHHC rat is caused by slowed down catabolism of cholesterol-rich very low density lipoprotein (VLDL). These cholesterol-rich particles are synthesized in the liver. We found out that PHHC rat fed 1% cholesterol diet accumulates cholesteryl esters (CE) in the liver and also in the VLDL. Acyl-CoA:cholesterol acyltransferase (ACAT) and microsomal triglyceride transfer protein (MTP) may participate in the increased incorporation CE into VLDL. We found out no difference in ACAT and MTP activities in the liver between PHHC rats and control animals. Neither ACAT activity...
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Knowledge of plasma lipids of university students, smokers
VARAUSOVÁ, Anežka Gabriela
Introduction: Cardiovascular diseases are among the most common causes of death. The risk factors include, among others, hypercholesterolemia. It has been long believed that a high level of cholesterol intake via meals (dietary cholesterol) has negative effects on the cardiovascular system and therefore it has been deliberately removed from diet. Several studies, however, confirm the assumption that cholesterol in diet (dietary cholesterol) has little effect on cholesterol levels in blood. The human body receives cholesterol through nourishment in form of animal fats, but it can produce it in the liver, too. So if cholesterol is removed from nourishment due to a diet, the liver can cover the need of cholesterol through increased production. Cholesterol level in the human body is influenced by many factors most of which we can control. These factors include food containing too much saturated fat or cholesterol, overweight, physical inactivity, congenital health conditions, age and gender. There are no symptoms of hypercholesterolemia at the first stage and that is why the current population does not pay such attention, which it should deserve, to hypercholesterolemia. Because there are a number of educational materials on this subject, I decided to explore among the university students (especially smokers) if they are interested in this subject and what their knowledge is. Objective: The main goal of my thesis was to map out the university students´ (smokers) knowledge of plasma lipids. The bachelor thesis was prepared by means of a quantitative research using questionnaires. The research sample consisted of 300 full-time students. I collected 270 filled-in questionnaires out of the 300 distributed. The questionnaire return rate was therefore 90%. 99 out of those 270 were unusable due to the fact that the respondents did not belong to the target group. The total number of questionnaires to be evaluated was 171 questionnaires. Results: I defined a research hypothesis. Hypothesis # 1 Knowledge of plasma lipids of university students, smokers is inadequate, has been confirmed. 36 (21%) respondents out of the total 171 respondents knew their level of cholesterol and 135 (79%) of the respondents did not know their level. Conclusion: This thesis can be used in practice as a publication, to increase the general awareness of students and professors of the issue of cholesterol. An educational material is attached to this thesis that can be used in general practitioners? surgeries.
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Influence of increased aplication of the file polyunsaturated fatty acids on alteration of level cholesterol of individuum.
FLANDERKOVÁ, Michaela
I have engaged in the influence of increased aplication of the file polyunsaturated fatty acids on alteration of level cholesterol of individuum in my bachelory work. At first I had studied theoretical knowledge focused the theme of polyunsatureted fatty acid and cholesterol. I had devoted to this knowledge in theoretical part of my bachelory work. After I had contacted some people. I had known that they have increased cholesterol level. This people I had acquainted with themes of my bachelory work and development of research. The acquainted people have accepted part of research. Initial measuring taked place after. The measuring determined the level of total cholesterol, LDL cholesterol, HDL cholesterol, triacylglycerol. The three month interventionist program taked place after, from march 2011 to december 2012. The Participant of research had consumed of food supplement, which contented fish oil. Fish oil is rich in content of polyunsaturated fatty acid omega 3 (EPA and DHA). Output measuring taked place after three month. On the basis of measuring got results. I worked with results in the practical part of my bachelory work. I have compared results of initial and output measuring.
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