Abstract
Background: Distribution of CYP2C9 and VKORC1 gene polymorphisms may vary significantly among different ethnic groups, and eventually influence the variation in drug metabolism or even failure. Objective: The aim of this study was to evaluate the prevalence of CYP2C9 and VKORC1 alleles in the healthy population of Republic of Macedonia compared to the global geographic data reported from different ethnic populations. Also, to genotype CYP2C9 and VKORC1 genes and eventually to divide individuals in poor, extensive, or intermediate metabolizer. Material and Methods: Blood samples were collected after signing written consent, DNA was isolated from peripheral blood, and CYP2C9 and VKORC1 genes were typed (n=124). Genotyping was performed by commercially available kits (GeneID GmbH, Strassberg, Germany, AID Diagnostica), based on the method of polymerase chain reaction with a subsequent hybridization. The population genetics analysis package, PyPop ver. 0.6.0, was used for analysis of the data. Results: The frequency of alleles varies from 0.931 for CYP2C9*3 to 0.109 for CYP2C9*2 indicating common wild type allele in those genes. The frequency ranges spanned ~50% for each allele of VKORC1 gene, indicating no common wild type allele in this gene. Test of neutrality showed significant negative value for VKORC1 polymorphism that indicates balancing selection operating on the alleles at that locus. All polymorphisms of CYP2C9*2, CYP2C9*3 and VKORC1 showed a good fit with Hardy-Weinberg expectations. Conclusion: The results of polymorphic alleles of CYP2C9 and VKORC1 genes in Macedonian population can be used for the variation in drug metabolism studies as well for adapting dosage regimes for oral anticoagulant therapies.
Highlights
The cytochrom P450 (CYP) family of heme monooxygenases comprise the most important group of Phase I enzymes
Frequencies of polymorphic alleles, test of neutrality with Fnd statistic [Ewens-Watterson test of neutrality (EWN)], and Slatkin’s Exact p-value (SEPV) with p of F statistics in macedonian population are shown on the Table 1
In this study we present the distribution of the common alleles of CYP2C9 that has been found to vary across populations and different ethnic groups
Summary
The cytochrom P450 (CYP) family of heme monooxygenases comprise the most important group of Phase I enzymes. These enzymes oxidize a wide range of endogenous, as well as exogenous compounds. The most important P450 isoenzyme is CYP3A4 (50% of the P450 metabolism) followed by CYP2D6 (20%), CYP2C9 and CYP2C19 (together 15%). The genes for CYP2D6, CYP2C9, CYP2C19 and CYP2A6 are functionally polymorphic. Approximately 40% of human P450 dependent drug metabolism is carried out by polymorphic enzymes (for a list of all currently known cytochrome P450 gene alleles go to http://www.cypalleles.ki.se/ ) [2]. Distribution of CYP2C9 and VKORC1 gene polymorphisms may vary significantly among different ethnic groups, and eventually influence the variation in drug metabolism or even failure
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
