Distribution of CYP2C9 and VKORC1 Gene Polymorphisms in Healthy Macedonian Male Population


  • Krume Jakjovski Institute of Preclinical and Clinical Pharmacology with Toxicology, Faculty of Medicine, Ss Cyril and Methodius University of Skopje
  • Nikola Labachevski Institute of Preclinical and Clinical Pharmacology with Toxicology, Faculty of Medicine, Ss Cyril and Methodius University of Skopje
  • Aleksandar Petlichkovski Institute of Immunobiology and Human Genetics, Faculty of Medicine, Ss Cyril and Methodius University of Skopje
  • Aleksandar Senev Institute of Immunobiology and Human Genetics, Faculty of Medicine, Ss Cyril and Methodius University of Skopje
  • Jasmina Trojacanec Institute of Preclinical and Clinical Pharmacology with Toxicology, Faculty of Medicine, Ss Cyril and Methodius University of Skopje
  • Emilija Atanasovska Institute of Preclinical and Clinical Pharmacology with Toxicology, Faculty of Medicine, Ss Cyril and Methodius University of Skopje
  • Elena Kostova Institute of Preclinical and Clinical Pharmacology with Toxicology, Faculty of Medicine, Ss Cyril and Methodius University of Skopje
  • Mirko Spiroski Institute of Immunobiology and Human Genetics, Faculty of Medicine, Ss Cyril and Methodius University of Skopje, Skopje http://orcid.org/0000-0001-5559-7981




gene polymorphisms, alleles, CYP2C9, VKORC1, genotyping, Macedonian population.


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.


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How to Cite

Jakjovski K, Labachevski N, Petlichkovski A, Senev A, Trojacanec J, Atanasovska E, Kostova E, Spiroski M. Distribution of CYP2C9 and VKORC1 Gene Polymorphisms in Healthy Macedonian Male Population. Open Access Maced J Med Sci [Internet]. 2013 Dec. 15 [cited 2021 Apr. 12];1(1):1-5. Available from: https://oamjms.eu/index.php/mjms/article/view/oamjms.2013.001



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