title: Characterization of the most common CYP2C9 and CYP2C19 allelic variants in the population from the Republic of Macedonia.
abstract: The aim of this study was to evaluate the most common CYP2C9 and CYP2C19 polymorphisms in the population of Macedonia and compare them with the global geographic data reported from different ethnic populations. In total, 184 healthy volunteers from the general population were included. Genotypes for the CYP2C9 (*2 [rs1799853] and *3[rs1057910]) and CYP2C19 (*2-[rs4244285] and *17 [rs12248560]) polymorphisms were detected by Real-Time PCR using TaqMan SNP genotyping assay. The CYP2C9 wildtype allele (*1) was the most frequent (78.8%) and the non-functional alleles *2 and *3 had a frequency of 13.9% and 7, 3%, respectively. Seven subjects (2.97%) were poor metabolites (PMs) for CYP2C9 because of the *2/*2 and *3/*3 genotype. For CYP2C19, the frequencies of the*1 (wild-type) and the non-functional alleles (*2 and *17) were 65.4%, 14.4% and 20.1%, respectively. The *2/*2 genotype, corresponded to the predicted frequency of 2.7% for the CYP2C19 PM phenotype. The total of 59 out of 184 subjects (32.0%) was determined as UMs because of the *1/*17 and *17/*17 genotypes. The compound heterozygote (*2/*17), which is associated with a difficult-to-predict phenotype, was detected in 8 subjects (4.34%). The CYP2C9 and CYP2C19 are polymorphic in the population of the Republic of Macedonia. The frequencies of the most common CYP2C9 and CYP2C19 allelic variants are similar to those reported for Caucasians of European descendant, but differ from those of North America Caucasians. Our results suggest that the genetically determined capacity of CYP2C9 and CYP2C19 has to be taken into account in order to improve the individual risk / benefit ratio of the drug therapy in Macedonia.
authors.affiliation: Department of Preclinical and Clinical Pharmacology and Toxicology, Faculty of Medicine, University Ss Cyril and Methodius, Skopje, Republic of Macedonia.
authors.forename: K
authors.initials: K
authors.lastname: Jakovski
authors.affiliation: Center for Bimolecular Pharmaceutical Analysis, Faculty of Pharmacy, University Ss Cyril and Methodius, Skopje, Republic of Macedonia.
authors.forename: A Kapedanovska
authors.initials: AK
authors.lastname: Nestorovska
authors.affiliation: Department of Preclinical and Clinical Pharmacology and Toxicology, Faculty of Medicine, University Ss Cyril and Methodius, Skopje, Republic of Macedonia.
authors.forename: N
authors.initials: N
authors.lastname: Labacevski
authors.affiliation: Center for Bimolecular Pharmaceutical Analysis, Faculty of Pharmacy, University Ss Cyril and Methodius, Skopje, Republic of Macedonia.
authors.forename: A J
authors.initials: AJ
authors.lastname: Dimovski
mesh_terms: D000328:Adult; D000483:Alleles; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics*; D065731:Cytochrome P-450 CYP2C19; D065729:Cytochrome P-450 CYP2C9; D004247:DNA / Q000235:genetics; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D005843:Geography; D006801:Humans; D008297:Male; D016133:Polymerase Chain Reaction; D018843:Republic of North Macedonia / Q000453:epidemiology
chemical_list: D004247:DNA; C450260:CYP2C9 protein, human; D065729:Cytochrome P-450 CYP2C9; D001189:Aryl Hydrocarbon Hydroxylases; C045793:CYP2C19 protein, human; D065731:Cytochrome P-450 CYP2C19