title: Frequency of single nucleotide polymorphisms of CYP2D6 in the Czech population.
abstract: CYP2D6 is a member of cytochrome P450 enzymes that metabolise over 25% of commonly used drugs. Genetic polymorphisms can cause insufficient drug efficacy at usually administered doses or can be the cause of adverse drug reaction. CYP2D6 genotyping can be used to predict CYP2D6 phenotype and thereby explain some abnormalities in drug response and thus optimize pharmacotherapy. The aim of this study was to investigate the frequency of functionally important variant alleles of the CYP2D6 gene throughout the Czech population to predict the prevalence of ultra-rapid and poor metabolizer phenotypes. The DNA of 223 unrelated, healthy volunteers was analysed to detect the presence of CYP2D6*6, *5, *4, *3 and gene duplication. The variant allele frequencies in our population were 0.22%, 3.14%, 22.87%, 1.12% and 3.14% for CYP2D6*6, CYP2D6*5, CYP2D6*4, CYP2D6*3 and CYP2D6*MxN, respectively. Fifteen subjects carried two variant alleles leading to predicted poor type of metabolism, 84 subjects were heterozygous extensive metabolizers (het-EM). The full-text contains detailed comparison with European white populations. The distribution of variant alleles complies with the Hardy-Weinberg equilibrium. The frequencies of functional variant alleles of CYP2D6 in Czech population are in concordance with other Caucasian populations.
authors.affiliation: Clinical Pharmacology Unit, Department of Pharmacology, First Faculty of Medicine, Charles University, Prague, Czech Republic. hbuzk@lf1.cuni.cz
authors.forename: Helena
authors.initials: H
authors.lastname: Buzková
authors.forename: Kristina
authors.initials: K
authors.lastname: Pechandová
authors.forename: Ondrej
authors.initials: O
authors.lastname: Slanar
authors.forename: Frantisek
authors.initials: F
authors.lastname: Perlík
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D019389:Cytochrome P-450 CYP2D6 / Q000235:genetics* / Q000502:physiology; D018153:Czech Republic; D005260:Female; D005787:Gene Frequency; D005828:Genetics, Population; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D004364:Pharmaceutical Preparations / Q000378:metabolism; D010597:Pharmacogenetics; D020641:Polymorphism, Single Nucleotide
chemical_list: D004364:Pharmaceutical Preparations; D019389:Cytochrome P-450 CYP2D6