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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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Analysis of gene polymorphism of CYP 2C19 patients treated with clopidogrel
MAŠKOVÁ, Soňa
Clopidogrel is an antithrombotic medicament from the group of thienopyrids, used for the prevention of blood cloths by the patients with acute coronary syndrome, patients after an ischemic stroke, myocardial infarction or by the patients with proven lower limb ischemia. Clopidogrel is a "prodrug", which means that it needs to be metabolised into an active metabolite before it stars working. The cytochrome P450 2C19 plays the main role in the bioactivation of clopidogrel. Individual enzymes of cytochrome complex are coded by genes, which are polymorphic. The function of P450 2C19 can differ by individuals, from the reason of gene polymorphism, therefore the bioactivation of clopidogrel can differ as well. There are few alleles of cytochrome P450 CYP2C19, which are connected with different therapeutic reactions on the submission of clopidogrel. Individuals with the allele CYP2C19*17 have an increased concentration of active metabolite and are at a higher risk of bleeding complications. The carriers of CYP2C19*2 a CYP2C19*3 alleles have a decreased metabolisation of clopidogrel into an active metabolite, which leads to insufficient antiaggregate effect and to increased appearance of cardiovascular complications. The allele CYP2C19*1 is connected with a fully functioning metabolism. In the group of 512 patients, we detected 191 carriers of the genotype *1/*1, 79 carriers of the genotype *2/*1, 12 carriers of the genotype *2/*2, 1 carrier of the genotype *3/*1, 43 carriers of the genotype *17/*17, 146 carriers of the genotype *17/*1 and 40 carriers of the genotype *17/*2. The stratification of the patients according to genotype CYP2C19 has a significant meaning for adjusting the right treatment strategy and it is a prevention of stroke and the risk of bleeding.
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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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