Gene geography of pharmacogenetically significant CYP2C19 cytochrome superfamily DNA markers in the populations of Russia and neighboring countries

Balanovska EV1, Abdulaev ShP2, Gorin IO1, Belov RO1, Mukatdarova EA1, Pylev VYu1,3
About authors

1 Research Centre for Medical Genetics, Moscow, Russia

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

3 Biobank of North Eurasia, Moscow, Russia

Correspondence should be addressed: Elena V. Balanovska
Moskvorechye, 1, 115522, Moscow, Russia; ur.liam@aksvonalab

About paper

Funding: the study was supported by the Russian Science Foundation grant № 21-14-00363 (bioinformatics, statistical and cartographic analysis), State Assignment of the Ministry of Science and Higher Education of the Russian Federation for the Research Centre for Medical Genetics (genealogical analysis, interpretation of the results).

Acknowledgements: the authors would like to thank all sample donors, who took part in the study, and Biobank of North Eurasia for access to DNA collections.

Author contribution: Balanovska EV — data analysis, manuscript writing, research management; Abdulaev ShP — discriptions of pharmacogenetic markers; Gorin IO — bioinformatics analysis; Belov RO — manuscript formatting; Mukatdarova EA — working with genealogical database; Pylev VYu — statistical analysis, cartographic analysis.

Compliance with ethical standards: the study was approved by the Ethics Commitee of the Research Centre for Medical Genetics (protocol № 1 of 29 June 2020); all subjects submitted the informed consent to study participation.

Received: 2023-09-18 Accepted: 2023-10-18 Published online: 2023-10-31

Genetic testing of each patient aimed at detecting the pharmacogenetic marker carrier state is challenging for healthcare system. However, knowledge about the frequencies of pharmacogenetically important genes enables making decisions about treatment based on the patient’s ethnicity. The CYP2C19 cytochrome gene involved in biotransformation of a broad spectrum of drugs is one of the most important. The study was aimed to determine the frequencies of major CYP2C19 variants and the patterns of their spatial variability in the population of Russia. The database Pharmacogenetics of the Population of Russia and Neighboring Countries created by the research team was used to determine frequencies of the CYP2C19 *1, *2, *3, *17 variants and their genotypes: *1 – 53 populations, n = 2261 samples; *2 — 79 populations, n = 6346; *3 — 92 populations, n = 7517; *17 — 35 populations, n = 3313. We have created a cartographic atlas that includes the *1, *2, *3, *17 frequency maps, correlation maps, and genotype frequency maps. Specific data on the frequencies of CYP2C19 variants and their pharmacogenetically significant genotypes in the major ethnic groups of Russia are provided. The cartographic atlas enables prediction of frequencies of significant CYP2C19 variants and their genotypes in the peoples, information about which is currently missing. The *1 and *2 variants gene geography is characterized by similar pattern: the combination of longitudinal trend of frequency increase from west to southeast and latitudinal variability of frequency increase from north to south in the Asian part of the region. Variant *3 is characterized by the clear longitudinal vector of frequency increase from 0 in the west to the world’s maximum in the Amur region. Variant *17 shows a pronounced longitudinal trend with the oppositely directed vector of frequency decrease from west to southeast. The correlation maps indicate regions, where the similarity between core patterns is disrupted.