vavilovВавиловский журнал генетики и селекцииVavilov Journal of Genetics and Breeding2500-3259Institute of Cytology and Genetics of Siberian Branch of the RAS10.18699/VJ18.348vavilov-1442Research ArticleМЕДИЦИНСКАЯ ГЕНЕТИКА, НЕЙРОГЕНЕТИКА, ИММУНОГЕНЕТИКА, БИОМЕДИЦИНАPOPULATION GENETICSПолиморфизм генов CYP1A1 и CYP2D6 в популяциях бурят, телеутов и у русских Восточной СибириGenetic polymorphism of CYP1A1 and CYP2D6 in populations of Buryats, Teleuts and Russians of Eastern SiberiaТабихановаЛ. Э.TabikhanovaL. E.

Новосибирск

Novosibirsk

tabikhan@bionet.nsc.ruОсиповаЛ. П.OsipovaL. P.

Новосибирск

Novosibirsk

ЧуркинаТ. В.ChurkinaT. V.

Новосибирск

Novosibirsk

ВоронинаЕ. Н.VoroninaE. N.

Новосибирск

Novosibirsk

ФилипенкоМ. Л.FilipenkoM. L.

Новосибирск

Novosibirsk

Федеральный исследовательский центр Институт цитологии и генетики Сибирского отделения Российской академии наукРоссияInstitute of Cytology and Genetics SB RASRussian FederationФедеральный исследовательский центр Институт цитологии и генетики Сибирского отделения Российской академии наук; Новосибирский национальный исследовательский государственный университетРоссияInstitute of Cytology and Genetics SB RAS; Novosibirsk State UniversityRussian FederationНовосибирский национальный исследовательский государственный университет; Институт химической биологии и фундаментальной медицины Сибирского отделения Российской академии наукРоссияNovosibirsk State University; Institute of Chemical Biology and Fundamental Medicine SB RASRussian Federation201806042018222205211Copyright © Табиханова Л.Э., Осипова Л.П., Чуркина Т.В., Воронина Е.Н., Филипенко М.Л., 20182018Табиханова Л.Э., Осипова Л.П., Чуркина Т.В., Воронина Е.Н., Филипенко М.Л.Tabikhanova L.E., Osipova L.P., Churkina T.V., Voronina E.N., Filipenko M.L.This work is licensed under a Creative Commons Attribution 4.0 License.https://vavilov.elpub.ru/jour/article/view/1442

Изучение полиморфизма генов системы биотрансформации ксенобиотиков в популяциях человека – важное направление современных медико-генетических исследований. Цель настоящей работы – определение частот аллелей генов CYP1A1 (A2455G (*2C), rs1048943), CYP2D6 (A2549del (*3), rs35742686); G1846A (*4), rs3892097) в популяциях телеутов (n = 115), восточных (n = 132) и западных (n = 280) бурят, их метисов (n = 56), а также в выборке русских Восточной Сибири (n = 122). Генотипирование проводили с помощью ПЦР в режиме реального времени с использованием конкурирующих TaqMan-зондов. Частота варианта CYP1A1*2С (2455G) составила в выборке восточных бурят 28.8 %, западных бурят 34.6 %, телеутов 16.7 %, в выборке метисов бурят 31.3 %. В выборке русских Восточной Сибири частота аллеля CYP1A1*2С (2455G) равна 4.1 %, что соответствует данным по другим европеоидным популяциям. Повышенный, по сравнению с русскими, популяционный риск развития заболеваний, вызываемых техногенными загрязнителями: диоксинами и полициклическими ароматическими углеводородами – субстратами цитохрома CYP1A1, прогнозируется как у телеутов, так и у бурят. Полиморфный вариант CYP2D6*3 (2549del) не выявлен в трех выборках коренных сибирских популяций – бурят и телеутов; среди русских его встречаемость 0.4 %, в выборке метисов – 2.7 %. Частота аллеля CYP2D6*4 (1846A) у восточных и западных бурят составляет 5.3 и 4.3 % соответственно, у телеутов – 7.4 %, в выборке русских она статистически значимо выше, чем у бурят, – 12 %, у метисов – 9.8 %. Прогнозируются пониженные, по сравнению с русскими, риски побочных эффектов лекарственных препаратов, а также онкологических заболеваний, ассоциированных с аллелями CYP2D6*3 (2549del) и CYP2D6*4 (1846A), у коренных жителей Южной и Восточной Сибири – бурят и телеутов. Однако метисация привносит в коренные популяции новые полиморфные варианты, сдвигает генные частоты и ведет к изменению степени рисков.

The study of the gene polymorphism of the system of biotransformation of xenobiotics is an important area of modern medical and genetic research. The aim of this work is to study the frequency of the alleles of the CYP1A1 (A2455G (*2C), rs1048943), CYP2D6 (A2549del (*3), rs35742686); G1846A (*4), rs3892097) genes of Teleuts (n = 115), Eastern Buryats (n = 132), Western Buryats (n = 280), their Métis (n = 56), and Russians of East Siberia (n = 122). Genotyping was performed using real-time PCR with competitive TaqMan allele-specific probes. The frequency of the CYP1A1*2C (2455G) allele was 28.8 % in the Eastern Buryat, 34.6 % in the Western Buryat, 16.7 % in the Teleut, and 31.3 % in the Métis cohort. The frequency of CYP1A1*2C (2455G) in the Russians of Eastern Siberia (4.1 %) corresponds to the frequency range found in European populations. A high-frequency occurrence of CYP1A1*2C (2455G) among Buryats and Teleuts may be indicative of a higher population-wide risk of diseases influenced by technogenic pollutants – substrates of CYP1A1. The CYP2D6*3 (2549del) allele was not detected in cohorts of indigenous populations, among Russians it was 0.4 %, and it was 2.7 % among Métis. The frequency of CYP2D6*4 (1846A) in Eastern and Western Buryats was 5.3 % and 4.3 %, respectively, for Teleuts it was 7.4 %. It was significantly higher in the Russian population (12 %), and among Métis (9.8 %). The obtained data makes it possible to predict a reduced risk of side effects of drugs and cancer associated with CYP2D6*3 (2549del) and CYP2D6*4 (1846A) in the Buryat and Teleut populations. However, metisation introduces new polymorphic variants into indigenous populations, shifts gene frequencies and changes the degree of risks.

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