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Frequency of occurrence of selected single nucleotide polymorphisms of CYP2C8 and MDR1 in the Czech population and their influence on the effect of amiodarone
Pechandová, Kristina ; Perlík, František (advisor) ; Král, Jiří (referee) ; Anzenbacher, Pavel (referee)
Frekvence výskytu vybraných bodových polymorfismů CYP2C8 a MDR1 v české populaci a jejich vliv na působení amiodaronu Úvod: Variabilita lékové odpovědi je někdy podmíněna genetickými rozdíly v metabolismu a transportu léčiv. Interindividuální rozdíly jsou často způsobeny polymorfismy, které ovlivňují biotransformační aktivitu enzymů a expresi transportérů. V disertační práci jsme věnovali pozornost cytochromu P450 izoenzymu CYP2C8 a MDR1. Nejprve jsme popsali frekvenci výskytu vybraných variantních alel CYP2C8*2, CYP2C8*3 (2 substituce v exonu 3 a 8, CYP2C8*3G416A a CYP2C8*3A1196G), CYP2C8*4, CYP2C8 P404A u zdravé české populace a variantních alel MDR1 v exonech: 26 C3435T, 21 G2677A/T, 12 C1236T a 17 T-76A. Následně jsme sledovali vliv těchto polymorfismů na působení amiodaronu u vybraného souboru pacientů. Metody: Genotyp MDR1 a CYP2C8 jsme stanovili pomocí PCR-RFLP za využití specifických restrikčních enzymů a primerů. Frekvence genotypů MDR1jsme určili u 189 zdravých dobrovolníků a CYP2C8 u 161 zdravých osob. Do sledování jsme dále zařadili 63 pacientů užívajících amiodaron déle než dva měsíce. Jejich léčbu jsme posuzovali ze záznamů lékařské dokumentace, s využitím standardních biochemických a hematologických vyšetření a záznamů EKG. Koncentrace amiodaronu a jeho metabolitu N-...
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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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Modelling of human palate surface development from 7 years to adulthood
Moravec, Tomáš ; Bejdová, Šárka (advisor) ; Zemková, Daniela (referee)
The diploma thesis deals with the differences in the development of the palate in girls and boys within five age groups in the age range of 7 to 19 years, using methods of geometric morphometry. Furthermore, the work deals with the monitoring of sexual dimorphism in the development of the palate. Understanding palate growth, knowledge of differences in its development and changes related to sexual dimorphism are very useful, as the results of this study will serve as a comparative standard for palate defects in the Czech population, but also for appropriate planning of orthodontic procedures. The material consists of 228 gypsum castings of palate without any pathologies, 112 of which belonged to boys and 116 girls of the Czech population. Thus, transverse data are used in our study. The subjects were divided into five age groups 7, 10, 12, 15 and 19 with respect to gender. Age changes of the entire palate surface were modeled using geometric morphometry methods (Coherent point drift - Dense correspondence analysis, Per vertex T- test and Principal component analysis). To visualize the results, superprojection color maps, maps of significance and superprojection. The results show the greatest variability in the form of palate in girls of groups 10 and 12 years and in boys of groups 10 years, and...
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Frequency of occurrence of selected single nucleotide polymorphisms of CYP2C8 and MDR1 in the Czech population and their influence on the effect of amiodarone
Pechandová, Kristina ; Perlík, František (advisor) ; Král, Jiří (referee) ; Anzenbacher, Pavel (referee)
Frequency of occurrence of selected single nucleotide polymorphisms of CYP2C8 and MDR1 in the Czech population and their influence on the effect of amiodarone Introduction: Variability in drug response is sometimes conditioned by genetic differences in the metabolism and the transport of drugs. Interindividual differences are often caused by polymorphisms affecting biotransformation activity of enzymes and expression of transporters. In the thesis we paid attention to the cytochrome P450 CYP2C8 and MDR1. First, we described the frequency of occurrence of selected variant alleles CYP2C8 * 2, CYP2C8 * 3 (2 substitution in exon 3 and 8, CYP2C8 and CYP2C8 * 3G416A * 3A1196G), CYP2C8 * 4, CYP2C8 P404A in the healthy Czech population and MDR1 variant alleles in these exons: 26 C3435T, 21 G2677A/T, 12 C1236T a 17 T-76A. Subsequently, we studied the influence of these polymorphisms on effects of amiodarone in the selected group of patients. Methods: We determined genotypes MDR1 a CYP2C8 by PCR-RFLP by using restriction enzymes and specific primers. We determined the frequency of MDR1 genotypes in 189 healthy volunteers and CYP2C8 in 161 healthy subjects. Further we included into the study 63 patients treated with amiodarone for longer than two months. Their treatment was assessed from medical records and...
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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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Frequency of occurrence of selected single nucleotide polymorphisms of CYP2C8 and MDR1 in the Czech population and their influence on the effect of amiodarone
Pechandová, Kristina ; Perlík, František (advisor) ; Král, Jiří (referee) ; Anzenbacher, Pavel (referee)
Frekvence výskytu vybraných bodových polymorfismů CYP2C8 a MDR1 v české populaci a jejich vliv na působení amiodaronu Úvod: Variabilita lékové odpovědi je někdy podmíněna genetickými rozdíly v metabolismu a transportu léčiv. Interindividuální rozdíly jsou často způsobeny polymorfismy, které ovlivňují biotransformační aktivitu enzymů a expresi transportérů. V disertační práci jsme věnovali pozornost cytochromu P450 izoenzymu CYP2C8 a MDR1. Nejprve jsme popsali frekvenci výskytu vybraných variantních alel CYP2C8*2, CYP2C8*3 (2 substituce v exonu 3 a 8, CYP2C8*3G416A a CYP2C8*3A1196G), CYP2C8*4, CYP2C8 P404A u zdravé české populace a variantních alel MDR1 v exonech: 26 C3435T, 21 G2677A/T, 12 C1236T a 17 T-76A. Následně jsme sledovali vliv těchto polymorfismů na působení amiodaronu u vybraného souboru pacientů. Metody: Genotyp MDR1 a CYP2C8 jsme stanovili pomocí PCR-RFLP za využití specifických restrikčních enzymů a primerů. Frekvence genotypů MDR1jsme určili u 189 zdravých dobrovolníků a CYP2C8 u 161 zdravých osob. Do sledování jsme dále zařadili 63 pacientů užívajících amiodaron déle než dva měsíce. Jejich léčbu jsme posuzovali ze záznamů lékařské dokumentace, s využitím standardních biochemických a hematologických vyšetření a záznamů EKG. Koncentrace amiodaronu a jeho metabolitu N-...
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STR genotyping of Czech medieval population: archeologocal site in Mlekojedy (Litoměřice)
Brynychová, Veronika ; Hájek, Martin (advisor) ; Šimková, Halina (referee)
The aim of this diploma thesis was the initial genetic analysis of early mediaeval burial site from Mlekojedy polycultural locality (Litoměřice District, Czech Republic). Autosomal STR markers were chosen because of the following reasons. The high degree of polymorphism of these markers and the high extent of heterozygosity favor the use of STRs instead of mitochondrial DNA for the structural analysis of small populations. Usefulness of STR typing for validation purposes was demonstrated many times before. We used primers for miniSTRs to obtain the fullest results. Nuclear DNA was extracted from 35 % of bone samples and 91 % of teeth. We detected lower PCR amplification success rate of fragments longer than 150 bp and very high rate of allele drop-out which is sign of degraded DNA. Twelve reliable genotypes were determined for TH01 marker. Observed allele frequency and genetic diversity values were discussed in comparison with recent populations and other aDNA studies of burial sites. Keywords: ancient DNA, STR markers, miniSTR, early medieval burial site, Czech population
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Approach to the life insurance from the perspective of Czech population
Loudová, Martina ; Jílek, Josef (advisor) ; Kubelková, Karina (referee)
The life insurance is an integral part of financial market, although changing its importance during the development. This thesis aims to carry out a research focused on the approach and attitude of the Czech population to the life insurance and its resulting analysis. The research was conducted through a questionnaire survey effected on an independent sample of the Czech population in the number of 185 respondents and a case study MetLife insurance company. The thesis does not neglect the theoretical background, current trends in the life insurance and the future prognosis. The results of analysis refer to the dependence of approach to the life insurance on the factors of age, the number of household members, the actual amount of outstanding liabilities and the gross monthly income. The lack of knowledge of respondents on the profitability, the risk and the liquidity of their life insurance policies and its dependence on the factor of achieved education were proved. In the case of a higher number of concluded life insurance contracts they diversify the risk and use different insurers. It also came out that the life insurance has recently kept losing its original meaning in the sense of risk instrument and is perceived still more as a savings and an invesment instrument. Although the current approach is not the rational reasoning, I continue to assume the increasing importance of unit linked life insurance.
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