Distribution of the most Common Genetic Variants Associated with a Variable Drug Response in the Population of the Republic of Macedonia.
Genetic variation in the regulation, expression and activity of genes coding for Phase I, Phase II drug metabolizing enzymes (DMEs) and drug targets, can be defining factors for the variability in both the effectiveness and occurrence of drug therapy side effects. Information regarding the geographic structure and multi-ethnic distribution of clinically relevant genetic variations is becoming increasingly useful for improving drug therapy and explaining inter-individual and inter-ethnic differences in drug response. This study summarizes our current knowledge about the frequency distribution of the most common allelic variants in three broad gene categories: the Phase I oxidation-cytochrome P450 (CYP450) family (CYP2C9, CYP2C19, CYP3A5, CYP2D6); the Phase II conjugation (GSTT1, SULT1A1; UGT1A1) and drug target (TYMS-TSER, MTHFR and VKORC1) in the population of the Republic of Macedonia and compares the information obtained with data published for other indigenous European populations. Our findings define the population of the Republic of Macedonia as an ethnic group with a highly polymorphic genetic profile. These results add to the evidence regarding the distribution of clinically important variant alleles in DME and drug target genes in populations of European ancestry.
Center for Biomolecular and Pharmaceutical Analysis, Faculty of Pharmacy, University Ss Cyril and Methodius, Skopje 1000, Republic of Macedonia.
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Kapedanovska Nestorovska
Department of Preclinical and Clinical Pharmacology and Toxicology, Faculty of Medicine, University Ss Cyril and Methodius, Skopje 1000, Republic of Macedonia.
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Jakovski
Center for Biomolecular and Pharmaceutical Analysis, Faculty of Pharmacy, University Ss Cyril and Methodius, Skopje 1000, Republic of Macedonia.
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Naumovska
Center for Biomolecular and Pharmaceutical Analysis, Faculty of Pharmacy, University Ss Cyril and Methodius, Skopje 1000, Republic of Macedonia.
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Hiljadnikova Bajro
Center for Biomolecular and Pharmaceutical Analysis, Faculty of Pharmacy, University Ss Cyril and Methodius, Skopje 1000, Republic of Macedonia.
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Sterjev
Center for Biomolecular and Pharmaceutical Analysis, Faculty of Pharmacy, University Ss Cyril and Methodius, Skopje 1000, Republic of Macedonia.
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Eftimov
Center for Biomolecular and Pharmaceutical Analysis, Faculty of Pharmacy, University Ss Cyril and Methodius, Skopje 1000, Republic of Macedonia.
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Matevska Geskovska
Center for Biomolecular and Pharmaceutical Analysis, Faculty of Pharmacy, University Ss Cyril and Methodius, Skopje 1000, Republic of Macedonia.
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Suturkova
Republic Institute for Transfusiology, Faculty of Medicine, University Ss Cyril and Methodius, Skopje 1000, Republic of Macedonia.
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Dimitrovski
Republic Institute for Transfusiology, Faculty of Medicine, University Ss Cyril and Methodius, Skopje 1000, Republic of Macedonia.
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Labacevski
Center for Biomolecular and Pharmaceutical Analysis, Faculty of Pharmacy, University Ss Cyril and Methodius, Skopje 1000, Republic of Macedonia.
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Dimovski
Allelic variants; Drug metabolizing enzymes (DMEs); Drug target; Republic of Macedonia