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

Abstract

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.

Ethnic Diversity and Warfarin Pharmacogenomics

“…Moreover, extrapolating a MAF from one population to another may not be straightforward as different variants may follow different geographical distribution patterns. For instance, Balanovskaya and others used a cartographic approach (2,197 participants representing 50 different populations/137 ethnic and subethnic groups) to visualize the geographic distribution of pharmacogenetic markers across Russia and its neighbouring countries and reported that: CYP2C9*2 followed a focal variation pattern [the CYP2C9*2 allele was specific to certain ethnicities (MAF as high as 0.23) and absent in others]; CYP2C9*3 followed a uniform pattern [MAF varying within a narrow range (0.03 to 0.10) in most ethnic groups]; and VKORC1 -1639G > A followed a clinal pattern [a gradient decrease in MAF (from >0.95 to ∼0.30) along the East-West axis] ( Balanovskaya et al, 2020 ).…”