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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