actabiomedicaActa Biomedica ScientificaActa Biomedica Scientifica2541-94202587-9596Scientific Centre for Family Health and Human Reproduction Problems10.29413/ABS.2018-3.5.6actabiomedica-705Research ArticleГЕНЕТИКА, ПРОТЕОМИКА И МЕТАБОЛОМИКАGENETICS, PROTEOMICS AND METABOLOMICSРАСПРОСТРАНЁННОСТЬ ПОЛИМОРФИЗМОВ ГЕНОВ ЦИТОХРОМОВ Р450 – МЕТАБОЛИЗАТОРОВ ВАРФАРИНА – В ВОСТОЧНОЙ СИБИРИFREQUENCIES OF POLYMORPHISMS IN THE CYTOCHROME’S P450 GENES OF WARFARIN TRANSFORMATION IN A EUROPEAN POPULATION OF EASTERN SIBERIAhttps://orcid.org/0000-0003-3704-830XБаироваТ. А.BairovaT. A.

664003, г. Иркутск, ул. Тимирязева, 16.

доктор медицинских наук, руководитель лаборатории персонализированной медицины.

ul. Timiryazeva 16, Irkutsk 664003.

Doctor of Medical Sciences, Head of the Laboratory of Personalized Medicine.

tbairova38@mail.ruhttps://orcid.org/0000-0002-9353-7928НовиковаЕ. А.NovikovaE. A.

664003, г. Иркутск, ул. Тимирязева, 16.

аспирант.

ul. Timiryazeva 16, Irkutsk 664003.

 Postgraduate.

europe411@mail.ruhttps://orcid.org/0000-0001-9131-6534БеляловФ. И.BelyalovF. I.

664049, г. Иркутск, Юбилейный, 100.

доктор медицинских наук, профессор кафедры геронтологии и гериатрии, руководитель Кардиоаритмологического центра.

Yubileynyi 100, Irkutsk 664049.

Doctor of Medical Sciences, Professor at the Department of Gerontology and Geriatrics, Head of the Center of Cardioarrhythmology.

ЩедрееваЕ. А.ShchedreevaE. A.

664043, г. Иркутск, б. Рябикова, 31А.

врач.

b. Ryabikova 31A, Irkutsk 664043.

Physician.

https://orcid.org/0000-0002-0177-234XИевлеваК. Д.IevlevaK. D.

664003, г. Иркутск, ул. Тимирязева, 16.

аспирант, врач клинической лабораторной диагностики.

ul. Timiryazeva 16, Irkutsk 664003.

Postgraduate, Physician at the Clinical Laboratory.

asiy91@mail.ruКалюжнаяО. В.KalyuzhnayaO. V.

664003, г. Иркутск, ул. Тимирязева, 16.

кандидат биологических наук, научный сотрудник лаборатории персонализированной медицины.

ul. Timiryazeva 16, Irkutsk 664003.

Candidate of Biological Sciences. Junior Research Officer at the Laboratory of Personalized Medicine.

kaluzhnayao@ya.ruЕршоваО. А.ErshovaO. A.

664003, г. Иркутск, ул. Тимирязева, 16.

кандидат биологических наук, научный сотрудник лаборатории персонализированной медицины.

ul. Timiryazeva 16, Irkutsk 664003.

Candidate of Biological Sciences, Research Officer at the Laboratory of Personalized Medicine.

oksana111088@mail.ruПустозеровВ. Г.PustozerovV. G.

664049, г. Иркутск, Юбилейный, 100.

664025, г. Иркутск, ул. Ленина, 20а.

кандидат медицинских наук, главный врач; заведующий кафедрой геронтологии и гериатрии.

Yubileynyi 100, Irkutsk 664049.

Candidate of Medical Sciences, Head Physician, Regional Geriatric Centre; Head of the Department of Gerontology and Geriatrics.

Dr.Pystozerov@bk.ruКовалеваО. А.KovalevaO. A.

664025, г. Иркутск, ул. Ленина, 20а.

врач.

ul. Lenina 20A, Irkutsk 664025.

Physician.

РаспутинаИ. В.RasputinaI. V.

664043, г. Иркутск, б. Рябикова, 31А.

врач.

b. Ryabikova 31A, Irkutsk 664043.

Physician.

НосковаИ. А.NoskovaI. A.

664058, г. Иркутск, Первомайский, 23А.

врач.

Pervomayskiy 23A, Irkutsk 664058.

Physician.

БатоговаТ. В.BatogovaT. V.

664043, г. Иркутск, б. Рябикова, 31А.

врач.

b. Ryabikova 31A, Irkutsk 664043.

Physician.

КузнецоваО. В.KuznetsovaO. V.

664043, г. Иркутск, б. Рябикова, 31А.

врач.

b. Ryabikova 31A, Irkutsk 664043.

Physician.

БогословаО. Ю.BogoslovaO. Yu.

664043, г. Иркутск, б. Рябикова, 31А.

врач.

b. Ryabikova 31A, Irkutsk 664043.

Physician.

https://orcid.org/0000-0003-2124-6328КолесниковС. И.KolesnikovS. I.

664003, г. Иркутск, ул. Тимирязева, 16.

119234, г. Москва, Ленинские Горы, 1.

академик РАН, заместитель главного учёного секретаря, Президиум РАН; профессор.

ul. Timiryazeva 16, Irkutsk 664003.

Leninskie Gory 1, Moscow 119234.

Academician of RAS, Deputy Chief Academic Secretary, Presidium of the Russian Academy of Sciences; Professor.

Sikolesnikov2012@gmail.comФГБНУ «Научный центр проблем здоровья семьи и репродукции человека».Scientific Сentre for Family Health and Human Reproduction Problems.Иркутская государственная медицинская академия последипломного образования – филиал ФГБОУ ДПО «Российская медицинская академия непрерывного профессионального образования» Минздрава России.Irkutsk State Medical Academy of Postgraduate Education – Branch Campus of the Russian Medical Academy of Continuing Professional Education.ОГАУЗ «Городская клиническая больница № 10».City Clinical Hospital N 10.Иркутская государственная медицинская академия последипломного образования – филиал ФГБОУ ДПО «Российская медицинская академия непрерывного профессионального образования» Минздрава России; ГБУЗ «Областной гериатрический центр».Irkutsk State Medical Academy of Postgraduate Education – Branch Campus of the Russian Medical Academy of Continuing Professional Education.ГБУЗ «Областной гериатрический центр».Regional Geriatric Centre.ОГБУЗ «Иркутская городская поликлиника № 4».Irkutsk City Polyclinic N 4.ФГБНУ «Научный центр проблем здоровья семьи и репродукции человека»; ФГБОУ ВО «Московский государственный университет имени М.В. Ломоносова».Scientific Сentre for Family Health and Human Reproduction Problems; Lomonosov Moscow State University.201828092018353948Copyright © Баирова Т.А., Новикова Е.А., Белялов Ф.И., Щедреева Е.А., Иевлева К.Д., Калюжная О.В., Ершова О.А., Пустозеров В.Г., Ковалева О.А., Распутина И.В., Носкова И.А., Батогова Т.В., Кузнецова О.В., Богослова О.Ю., Колесников С.И., 20182018Баирова Т.А., Новикова Е.А., Белялов Ф.И., Щедреева Е.А., Иевлева К.Д., Калюжная О.В., Ершова О.А., Пустозеров В.Г., Ковалева О.А., Распутина И.В., Носкова И.А., Батогова Т.В., Кузнецова О.В., Богослова О.Ю., Колесников С.И.Bairova T.A., Novikova E.A., Belyalov F.I., Shchedreeva E.A., Ievleva K.D., Kalyuzhnaya O.V., Ershova O.A., Pustozerov V.G., Kovaleva O.A., Rasputina I.V., Noskova I.A., Batogova T.V., Kuznetsova O.V., Bogoslova O.Y., Kolesnikov S.I.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.actabiomedica.ru/jour/article/view/705Обоснование

Обоснование. Гены ферментов цитохрома Р450 участвуют в метаболизме непрямых антикоагулянтов, определяя индивидуальную чувствительность к варфарину. Распространённость полиморфизмов указанных генов вариативна в разных расах и этнических группах.

Цель исследования

Цель исследования: выявление распространённости носителей генотипов и аллелей полиморфизмов генов биотрансформации варфарина – ферментов цитохрома Р450 (CYP2C9 (rs1799853, rs1057910), гена CYP4F2 (rs2108622)) среди европеоидов Восточной Сибири.

Методы

Методы. Участники исследования – 147 пациентов (европеоидов), принимающих варфарин для профилактики тромбоэмболических осложнений: при фибрилляции предсердий – 77 (52,38 %) человек; после имплантации искусственного механического клапана – 15 (10,20 %); при ишемической болезни сердца – 10 (6,80%); после ТЭЛА – 5 (3,40 %) и др. Средний возраст обследованных – 64,74 ± 14,29 лет; 67 (45,58 %) мужчин, 80 (54,42 %) женщин. Генотипирование каждого образца проводили методом полимеразной цепной реакции в режиме реального времени (РТ-ПЦР) с использованием наборов реагентов «ФармакоГенетикаВарфарин» (ДНКтехнология, Россия). Амплификацию проводили на приборе «ДТ-прайм» (ДНК-технология, Россия).

Результаты

Результаты. Среди европеоидов Восточной Сибири распространённость носителей двух функциональных аллелей (*1/*1) (экстенсивные/нормальные метаболизаторы) составляет 69,4 %, промежуточных метаболизаторов (*1/*2; *1/*3) – 29,8 %, медленных метаболизаторов (*3/*3) – 0,68 %. Отсутствуют гомозиготные носители двух нефункциональных аллелей *2 и *3 (*2/*2, *2/*3). Для гена CYP4F2 носительство одной кумаринорезистентной аллели выявлено у 57 (38,7 %) респондентов, двух кумаринорезистентных аллелей – у 10 (6,8 %) респондентов.

Заключение

Заключение. Распространённость рисковых аллелей генов ферментов системы цитохромов Р450, принимающих участие в биотрансформации варфарина, сопоставима с аналогичными показателями в других европеоидных популяциях мира.

Background

Background. Genotypes of the cytochrome p450 isoform (CYP2C9 and CYP4F2) determine warfarin dose requirements. Frequencies of risk alleles and genotypes of CYP2C9 and CYP4F2 gene vary in different races and ethnic groups.

Aim

Aim. This study analyzed the frequencies of *2, *3 alleles of CYP2C9 gene and the 1347 C>T allele of CYP4F2 gene in the Caucasians of Eastern Siberia, and compare with other populations.

Materials and methods

Materials and methods. Participants were 147 patients (Caucasians): 67 (45.58 %) man and 80 (54.42 %) women), taking warfarin for the prevention of thrombosis with a mean age of 64.74 ± 14.29 years. There were patients with atrial fibrillation – 77 (52.38 %) persons, coronary artery disease – 10 (6.80 %), pulmonary embolism – 5 (3.40 %), 15 (10.20 %) patients after implantation of an mechanical heart valve, etc. The subjects were genotyped for CYP2C9 (*1,*2,*3), and CYP4F2 (1347 C>T) by real-time polymerase chain reaction (RT-PCR) using “Pharmacogenetics Warfarin” reagent kits (DNA technology, Russia).

Results

Results. 69.4 % of Caucasians of Eastern Siberia (Russians), have two functional alleles (*1/*1) of CYP2C9 (they’re extensive/normal metabolizers), the number of intermediate metabolizers (*1/*2, *1/*3) was 29.8 % and 0.68 % of slow metabolizers (*3/*3). Homozygous carriers of two non-functional alleles *2 and *3 (*2/*2, *2/*3) were absent. Carriers of one coumarin-resistant Т-allele of CYP4F2 were 57 (38.7 %) respondents, two coumarin-resistant alleles – 10 (6.8 %) respondents.

Conclusions

Conclusions. Frequencies of polymorphisms in the Cytochrome’s p450 genes of warfarin transformation in a European population of Eastern Siberia have no differences with other European populations of the world

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