Cartographic atlas of frequency variation for 45 pharmacogenetic markers in populations of Russia and its neighbor states

Balanovska EV1,2, Petrushenko VS1,3, Koshel SM1,4, Pocheshkhova EA1,5, Chernevskiy DK1, Mirzaev KB6, Abdullaev ShP6, Balanovsky OP1,2,3
About authors

1 Bochkov Research Center for Medical Genetics, Moscow, Russia

2 Biobank of North Eurasia, Moscow, Russia

3 Vavilov Institute of General Genetics, Moscow, Russia

4 Lomonosov Moscow State University, Moscow, Russia

5 Kuban State Medical Institute, Krasnodar, Russia

6 Russian Medical Academy of Continuous Professional Education, Moscow, Russia

Correspondence should be addressed: Elena B. Balanovska
Moskvorechie, 1, Moscow, 115478; ur.liam@aksvonalab

About paper

Funding: the study was carried out under the State Assignment of the Russian Ministry of Science and Higher Education for the Research Center for Medical Genetics and Vavilov Institute of General Genetics.

Acknowledgement: the authors thank the donors for their participation, the Institute of General Genetics for the access to the database of genotypes, the Center for Precision Genome Editing and Genetic Technologies for Biomedicine of Pirogov Russian National Research Medical University (Moscow, Russia) for the opportunity to usemolecular genetic technologies.

Author contribution: Balanovska EV — data analysis, manuscript draft; Balanovsky OP — study design and supervision; Petrushenko VS — bioinformatic analysis; Koshel SM — map analysis, manuscript editing; Chernevskiy DK, Pocheshkhova EA — tabular data analysis; Mirzaev KB, Abdullaev SP — description of pharmacogenetic markers.

Compliance with ethical standards: the study was approved by the Ethics Committee of the Research Center for Medical Genetics (Protocol № 3/1 dated September 5, 2018) and carried out on the samples obtained during the population genetic study of the gene pools of ethnic groups from Russia and its neighbor states. The donors gave voluntary informed consent to participate.

Received: 2020-11-06 Accepted: 2020-11-22 Published online: 2020-12-18

The lack of information about the frequency of pharmacogenetic markers in Russia impedes the adoption of personalized treatment algorithms originally developed for West European populations. The aim of this paper was to study the distribution of some clinically significant pharmacogenetic markers across Russia. A total of 45 pharmacogenetic markers were selected from a few population genetic datasets, including ADME, drug target and hemostasis-controlling genes. The total number of donors genotyped for these markers was 2,197. The frequencies of these markers were determined for 50 different populations, comprised of 137 ethnic and subethnic groups. A comprehensive pharmacogenetic atlas was created, i.e. a systematic collection of gene geographic maps of frequency variation for 45 pharmacogenetic DNA markers in Russia and its neighbor states. The maps revealed 3 patterns of geographic variation. Clinal variation (a gradient change in frequency along the East-West axis) is observed in the pharmacogenetic markers that follow the main pattern of variation for North Eurasia (13% of the maps). Uniform distribution singles out a group of markers that occur at average frequency in most Russian regions (27% of the maps). Focal variation is observed in the markers that are specific to a certain group of populations and are absent in other regions (60% of the maps). The atlas reveals that the average frequency of the marker and its frequency in individual populations do not indicate the type of its distribution in Russia: a gene geographic map is needed to uncover the pattern of its variation.

Keywords: pharmacogenetics, gene pool, cartographic atlas, populations, ethnic groups, gene geography, Russia, North Eurasia