mesЭкстремальная биомедицинаExtreme Medicine2713-27572713-2765Centre for Strategic Planning of the Federal Medical and Biological Agency10.47183/mes.2025-371mes-371Research ArticleГЛАВНАЯ ТЕМА: ГЕНОМНЫЕ И ПОСТГЕНОМНЫЕ ТЕХНОЛОГИИ КАК ОСНОВА РАЗВИТИЯ ПЕРСОНАЛИЗИРОВАННОЙ МЕДИЦИНЫMAIN TOPIC: GENOMIC AND POST-GENOMIC TECHNOLOGIES AS A BASIS FOR THE DEVELOPMENT OF PERSONALIZED MEDICINEАллельные варианты цитохромов CYP2C9, CYP2C19, CYP2D6 у жителей России: распространенность и региональное распределениеAllelic variants of CYP2C9, CYP2C19, CYP2D6 cytochromes in the Russian population: Prevalence and regional distributionhttps://orcid.org/0000-0002-9199-6258ЮдинВ. С.YudinV. S.

Юдин Владимир Сергеевич, канд. биол. наук

Москва

Vladimir S. Yudin, Cand. Sci. (Biol.)

Moscow

VYudin@cspfmba.ruhttps://orcid.org/0000-0003-0714-9476СпекторЕ. Д.SpektorE. D.

Спектор Екатерина Дмитриевна, канд. мед. наук

Москва

Ekaterina D. Spektor, Cand. Sci. (Med.)

Moscow

espektor@cspfmba.ruhttps://orcid.org/0000-0002-6025-7663МамчурА. А.MamchurA. A.

Мамчур Александра Александровна

Москва

Aleksandra A. Mamchur

Moscow

AMamchur@cspfmba.ruhttps://orcid.org/0009-0004-7070-5636ИвановМ. В.IvanovM. V.

Иванов Михаил Вячеславович

Москва

Mikhail V. Ivanov

Moscow

MIvanov@cspfmba.ruhttps://orcid.org/0000-0003-0358-0568МитрофановС. И.MitrofanovS. I.

Митрофанов Сергей Игоревич, канд. биол. наук

Москва

Sergey I. Mitrofanov, Cand. Sci. (Biol.)

Moscow

Mitrofanov@cspfmba.ruКузьминаЛ. П.KuzminaL. P.

Кузьмина Людмила Павловна, д-р мед. наук, профессор

Москва

Ludmila P. Kuzmina, Dr. Sci. (Med.), Professor

Moscow

kuzmina@irioh.ruhttps://orcid.org/0000-0002-8317-2718БухтияровИ. В.BukhtiyarovI. V.

Бухтияров Игорь Валентинович, д-р мед. наук, профессор

Москва

Igor V. Bukhtiyarov, Dr. Sci. (Med.), Professor

Moscow

bukhtiyarov@irioh.ruhttps://orcid.org/0000-0001-7378-983XКескиновА. А.KeskinovA. A.

Кескинов Антон Артурович, канд. мед. наук

Москва

Anton A. Keskinov, Cand. Sci (Med.)

Moscow

Keskinov@cspfmba.ruhttps://orcid.org/0000-0002-7942-8004ЮдинС. М.YudinS. M.

Юдин Сергей Михайлович, д-р мед. наук, профессор

Москва

Sergey M. Yudin, Dr. Sci. (Med.), Professor

Moscow

info@cspfmba.ruhttps://orcid.org/0000-0001-8977-4384КаштановаД. А.KashtanovaD. A.

Каштанова Дарья Андреевна, канд. мед. наук

Москва

Daria A. Kashtanova, Cand. Sci. (Med.)

Moscow

DKashtanova@cspfmba.ruЦентр стратегического планирования и управления медико-биологическими рисками здоровью Федерального медико-биологического агентстваРоссияCentre for Strategic Planning and Management of Biomedical Health Risks of the Federal Medical and Biological AgencyRussian FederationНаучно-исследовательский институт медицины труда им. академика Н.Ф. ИзмероваРоссияIzmerov Research Institute of Occupational HealthRussian Federation2026240320262813750Copyright © Юдин В.С., Спектор Е.Д., Мамчур А.А., Иванов М.В., Митрофанов С.И., Кузьмина Л.П., Бухтияров И.В., Кескинов А.А., Юдин С.М., Каштанова Д.А., 20262026Юдин В.С., Спектор Е.Д., Мамчур А.А., Иванов М.В., Митрофанов С.И., Кузьмина Л.П., Бухтияров И.В., Кескинов А.А., Юдин С.М., Каштанова Д.А.Yudin V.S., Spektor E.D., Mamchur A.A., Ivanov M.V., Mitrofanov S.I., Kuzmina L.P., Bukhtiyarov I.V., Keskinov A.A., Yudin S.M., Kashtanova D.A.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.extrememedicine.ru/jour/article/view/371Введение

Введение. Определение генотипа CYP2C9, CYP2C19, CYP2D6 позволяет персонализировать терапию для широкого круга лекарственных средств. Доступные в настоящий момент диагностические панели и международные рекомендации, регламентирующие объем тестирования, базируются на общемировых данных об аллельном полиморфизме этих генов.

Цель

Цель. Определение распределения аллельных вариантов генов CYP2C9, CYP2C19 и CYP2D6 в популяции жителей РФ с учетом региональных особенностей.

Материалы и методы

Материалы и методы. Исследование выполнено на выборке из базы данных популяционных частот (GBD) ЦСП ФМБА России (n = 121 442, охват 85 субъектов РФ). Всем участникам выполнено полногеномное секвенирование ДНК, установление генотипа CYP2C9, CYP2C19 и CYP2D6 при помощи программного обеспечения PAnno. В регионах с достаточным количеством наблюдений сопоставляли частоты вариантов и доли различных фенотипов метаболизма с выделением регионов риска и регионов с аллельной структурой, отличающейся от популяционной.

Результаты

Результаты. Распространенность замедленного метаболизма субстратов CYP2C9 в популяции оценивается в 33,66%, CYP2C19 — в 25,37%, CYP2D6 — в 8,29%, ускоренного метаболизма субстратов CYP2C19 — в 37,37%. К регионам риска наличия замедленного метаболизма субстратов хотя бы одного из исследуемых изоферментов относятся Чеченская Республика, Дагестан, Ингушетия, Кабардино-Балкария, Северная Осетия, Ростовская область, Чувашия, Марий Эл, Удмуртская Республика, Татарстан, Тыва, Якутия, Калмыкия, Бурятия, Карелия, Сахалинская, Иркутская и Новосибирская области. Данный риск реализуется как за счет количественных различий во встречаемости частых аллельных вариантов, так и за счет представленности в отдельных регионах редких аллелей, таких как CYP2C9*29, CYP2C9*12, CYP2C19*8, CYP2D6*32, CYP2D6*7.

Выводы

Выводы. Полученные результаты создают предпосылки для разработки отечественных диагностических панелей, а также для дифференцированного подхода к фармакогенетическому тестированию в разных биогеографических группах внутри страны, внедрение которых должно сопровождаться клинико-экономическим обоснованием для каждого препарата, чья эффективность или безопасность существенно зависят от генотипа CYP2C9, CYP2C19 и CYP2D6.

Introduction

Introduction. Determination of the CYP2C9, CYP2C19, and CYP2D6 genotypes enables therapy personalization for a wide range of medications. The currently available diagnostic panels and international guidelines governing the scope of testing are based on global data concerning the allelic polymorphism of these genes.

Objective

Objective. To determine the distribution of allelic variants of the CYP2C9, CYP2C19, and CYP2D6 genes in the population of the Russian Federation, taking regional characteristics into account.

Materials and methods

Materials and methods. The study was conducted on a sample from the Genetic Database (GDB) of the Centre for Strategic Planning and Management of Biomedical Health Risks (n = 121,442, covering 85 Russian federal subjects). Whole-genome DNA sequencing was performed for all participants, with CYP2C9, CYP2C19, and CYP2D6 genotyping determined using the PAnno software. In regions with a sufficient number of observations, variant frequencies and the proportions of different metabolic phenotypes were compared, identifying high-risk regions and those with an allelic structure differing from the overall population.

Results

Results. The prevalence of impaired metabolism for CYP2C9 substrates in the population is estimated at 33.66%, for CYP2C19 at 25.37%, and for CYP2D6 at 8.29%. The prevalence of accelerated metabolism for CYP2C19 substrates is 37.37%. The following regions are identified as high-risk for the presence of impaired metabolism of substrates for at least one of the studied isoenzymes: the Republics of Chechnya, Dagestan, Ingushetia, Kabardino-Balkaria, North Ossetia, Chuvashia, Mari El, Udmurtia, Tatarstan, Tyva, Sakha (Yakutia), Kalmykia, Buryatia, Karelia, as well as Rostov Oblast, Sakhalin Oblast, Irkutsk Oblast, and Novosibirsk Oblast. This risk manifests due to both quantitative differences in the frequency of common allelic variants and the presence of rare alleles in specific regions, such as CYP2C9*29, CYP2C9*12, CYP2C19*8, CYP2D6*32, and CYP2D6*7.

Conclusions

Conclusions. The obtained results provide the basis for the development of domestic diagnostic panels and for implementing a differentiated approach to pharmacogenetic testing across various biogeographic groups within the country. The introduction of such panels must be accompanied by health economic evaluation for each drug whose effectiveness and safety depends substantially on the CYP2C9, CYP2C19, and CYP2D6 genotype.

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The authors declare that there are no conflicts of interest present.