vestimИзвестия Национальной академии наук Беларуси. Серия медицинских наукProceedings of the National Academy of Sciences of Belarus, Medical series1814-60232524-2350The Republican Unitary Enterprise Publishing House "Belaruskaya Navuka"10.29235/1814-6023-2021-18-2-147-159vestim-756Research ArticleКЛИНИЧЕСКАЯ И ЭКСПЕРИМЕНТАЛЬНАЯ МЕДИЦИНАCLINICAL AND EXPERIMENTAL MEDICINEВлияние полиморфизма генов тромбоцитарных рецепторов P2RY12, ITGB3 и фермента-метаболизатора цитохрома CYP2C19 на активность тромбоцитов и эффективность клопидогрела у пациентов со стабильной стенокардией напряжения, проживающих в Гродненском регионеEffect of polymorphism of platelet receptors genes P2RY12, ITGB3 and CYP2C19 cytochrome metabolizer enzyme on the platelet activity and efficiency of clopidogrel in patients with stable stenocardia in the Grodno regionПронькоТ. П.PronkoT. P.

Пронько Татьяна Павловна ‒ канд. мед. наук, доцент, заведующий кафедрой

ул. Горького, 80, 230009, г. Гродно

Tatyana P. Pronko ‒ Ph. D. (Med.), Associate Professor, Head of the Department

80, Gorky Str., 230009, Grodno 

tanya_pronko@mail.ruСнежицкийВ. А.SnezhitskiyV. A.

Снежицкий Виктор Александрович ‒ член-корреспондент, д-р мед. наук, профессор

ул. Горького, 80, 230009, г. Гродно

Viktor A. Snezhitskiy ‒ Corresponding Member, D. Sc. (Med.), Professor

80, Gorky Str., 230009, Grodno 

vsnez@mail.ruГорчаковаО. В.GorchakovaO. V.

Горчакова Ольга Владимировна ‒ магистр мед. наук, науч. сотрудник

ул. Горького, 80, 230009, г. Гродно 

Olga V. Gorchakova – Master of Medicine, Researcher

80, Gorky Str., 230009, Grodno 

daniil_go@inbox.ruСтепуроТ. Л.StepuroT. L.

Степуро Татьяна Леонидовна ‒ канд. мед. наук, доцент

ул. Горького, 80, 230009, г. Гродно

Tatyana L. Stepuro ‒ Ph. D. (Med.), Associate Professor

80, Gorky Str., 230009, Grodno 

mikhno_t@yahoo.comГладкийМ. Л.GladkiyM. L.

Гладкий Максим Леонидович ‒ аспирант

ул. Горького, 80, 230009, г. Гродно 

Maxim L. Gladkiy ‒ Postgraduate student

80, Gorky Str., 230009, Grodno 

cnil@grsmu.byГродненский государственный медицинский университетGrodno State Medical University202104062021182147159Copyright © Пронько Т.П., Снежицкий В.А., Горчакова О.В., Степуро Т.Л., Гладкий М.Л., 20212021Пронько Т.П., Снежицкий В.А., Горчакова О.В., Степуро Т.Л., Гладкий М.Л.Pronko T.P., Snezhitskiy V.A., Gorchakova O.V., Stepuro T.L., Gladkiy M.L.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://vestimed.belnauka.by/jour/article/view/756

Цель исследования – оценка распространения полиморфных вариантов G681A гена CYP2C19, H1/H2 гена P2RY12, T1565C гена ITGB3 и изучение их влияния на активность тромбоцитов и эффективность клопидогрела у пациентов со стабильной стенокардией напряжения (ССН), проживающих в Гродненском регионе. В исследование было включено 92 пациента с ССН, 89 из которых подверглись процедуре планового чрескожного коронарного вмешательства, и 93 практически здоровых человека. Данные обследований (общеклинических, агрегометрии, общего анализа крови и тромбоцитарных индексов, генотипирования методом полимеразной цепной реакции) проанализированы с использованием программы STATISTICA 10.0.В выборке лиц Гродненского региона выявлена высокая распространенность носительства генотипов, ассоциированных с возможной вариабельностью ответа на терапию клопидогрелем, как среди пациентов со стабильной стенокардией, так и среди практически здоровых лиц. Частота встречаемости указанных генотипов среди пациентов со стабильной стенокардией составила 23,9 % для гена CYP2C19 (полиморфный локус G681A), 40,2 % для гена P2RY12 (полиморфный локус H1/H2), 31,5 % для гена ITGB3 (полиморфный локус T1565C), среди практически здоровых лиц ‒ 18,3; 46,2; 37,6 % соответственно. Выявлены ассоциации между носительством аллеля 681A гена CYP2C19 и гаплотипа Н2 гена P2RY12 и высокой остаточной реактивностью тромбоцитов на фоне терапии клопидогрелем у пациентов с ССН. Обнаружена ассоциация между носительством гаплотипа Н2 полиморфизма Н1/Н2 гена P2RY12 с высокими значениями MPV тромбоцитов и более высокой частотой встречаемости крупных тромбоцитов (P-LCR) у пациентов с ССН.

The aim of the study was to assess the distribution of polymorphic variants G681A of the CYP2C19 gene, H1/H2 of the P2RY12 gene, and T1565C of the ITGB3 gene and to study their effect on the platelet activity and clopidogrel efficacy in patients with stable stenocardia living in the Grodno region. The study included 92 patients with stable stenocardia, 89 of them underwent elective percutaneous coronary intervention (PCI), and 93 practically healthy people. The survey data (general clinical, aggregometry, general blood count and platelet indices, and polymerase chain reaction genotyping) were analyzed using the STATISTICA 10.0 software.A high prevalence of carriage of genotypes associated with possible variability in response to clopidogrel therapy was revealed both among patients with stable stenocardia and among practically healthy individuals in the Grodno region. The frequency of occurrence of studying genotypes among patients with stable stanocardia was 23.9 % for the CYP2C19 gene (polymorphic locus G681A), 40.2 % for the P2RY12 gene (polymorphic locus H1/H2), and 31.5 % for the gene ITGB3 (polymorphic locus T1565C). For the group of practically healthy individuals, the distribution of these genotypes was 18.3; 46.2; 37.6 %, respectively. Associations were revealed between the carriage of the 681A allele of the CYP2C19 gene and the H2 haplotype of the P2RY12 gene with high residual platelet reactivity during clopidogrel therapy in patients with stable stenocardia. An association was found between the carriage of the H2 haplotype of the H1/H2 polymorphism of the P2RY12 gene with high platelet MPV values and a higher frequency of large platelets (P-LCR) in patients with stable stenocardia.

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