DISTRIBUTION OF THE MOST COMMON GENETIC VARIANTS ASSOCIATED WITH A VARIABLE DRUG RESPONSE IN THE POPULATION OF THE REPUBLIC OF MACEDONIA
Kapedanovska Nestorovska A1, Jakovski K2, Naumovska Z1, Hiljadnikova Bajro M1, Sterjev Z1, Eftimov A1, Matevska Geskovska N1, Suturkova L1, Dimitrovski K3, Labacevski N3, Dimovski AJ
*Corresponding Author: Aleksandar J. Dimovski, MD., Ph.D., Center for Biomolecular and Pharmaceutical Analysis, Faculty of Pharmacy, University Ss Cyril and Methodius, Mother Theresa 47, Skopje 1000, Republic of Macedonia. Tel: +389-2-3217-580; +389-2-3119-694. Fax: +389-2-3290-830; +389-2-3123 054. E-mail: adimovski@ff.ukim.edu.mk
page: 5
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Abstract

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.



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