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

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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