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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CONCLUSIONS
Different populations or ethnic groups are likely
to be more similar than different to each other. However,
inter-individual differences in drug responses
are well recognized and may be due to genetic or
environmental influences. These contributing factors
may also result in inter-ethnic or inter-geographic
differences in drug response.
In addition, regional differences in the frequency
of CYP450 genetic variants leading to population specific
DME activity patterns have been observed. Altogether,
at least 28 out of 42 DMEs show differences
between ethnically defined populations [12]. Several
lines of evidence imply that the effect of demography
on pharmacogenetic variations should be considered
even on a microgeographic scale, especially
when population sizes are small [5]. Thus, information
regarding geographic structure and multi-ethnic
distribution of clinically relevant genetic variations
is becoming increasingly useful for improving drug
therapy and explaining inter-individual and interethnic
differences in drug response [4,5].
Given the recognized ethnic differences in drug
responses and the fact that many genetic polymorphisms
differ in frequency on the basis of ethnicity/
ancestry [7], it is not surprising that the inter-ethnic
comparisons of drug response have become a major
aspect of pharmacogenetics. Furthermore, the experts
advise a careful consideration of the appropriate usage
of drugs in populations where known ethnic differences
occur and where genetic determinants may or
may not be elucidated. Most of the European ethnic groups have already reported the frequency of the
above mentioned genetic polymorphisms, but data
regarding the distribution in the normal population
of the Republic of Macedonia are deficient.
This study is the first to have reviewed and summarized
the current knowledge about the frequency
distribution of the most common allelic variants in three
broad gene categories: Phase I-oxidation, CYP450
family (CYP2C9, CYP2C19, CYP3A5, CYP2D6),
Phase II conjugation (GSTT1, SULT1A1, UGT1A1)
and drug target (TYMS-TSER, MTHFR and VKORC1)
in a population of the Republic of Macedonia compared
to those reported for 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 with European ancestry. They may serve
as a background for comparison with other population
samples and could be included in case-control studies
as a reference for Macedonian population.
Declaration of Interest. The authors report no
conflicts of interest. The authors alone are responsible
for the content and writing of this article.
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