cardiotomskСибирский журнал клинической и экспериментальной медициныSiberian Journal of Clinical and Experimental Medicine2713-29272713-265XTSU publishing10.29001/2073-8552-2021-36-4-125-131cardiotomsk-1297Research ArticleЭКСПЕРИМЕНТАЛЬНЫЕ ИССЛЕДОВАНИЯEXPERIMENTAL STUDIESАссоциации rs4244285 в гене CYP2C19 с многофакторными заболеваниямиAssociations of rs4244285 in the CYP2C19 gene with multifactorial diseaseshttps://orcid.org/0000-0001-6133-8986БабушкинаН. П.BabushkinaN. P.

 канд. биол. наук, научный сотрудник, лаборатория  популяционной генетики

 634050, Российская Федерация, Томск, наб. реки Ушайки, 10 

 Cand. Sci. (Biol.), Research Scientist, Laboratory of Population Genetics

 10, Nab. Ushaiki, Tomsk, 634050, Russian Federation 

nad.babushkina@medgenetics.ruhttps://orcid.org/0000-0002-5144-001XПостриганьА. Е.PostriganA. E.

 младший научный сотрудник, лаборатория геномики орфанных болезней  

634050, Российская Федерация, Томск, наб. реки Ушайки, 10 

 Junior Research Scientist, Laboratory of Genomics of Orphan Diseases 

 10, Nab. Ushaiki, Tomsk, 634050, Russian Federation 

postrigan.anna@medgenetics.ruhttps://orcid.org/0000-0003-3824-3641КучерА. Н.KucherA. N.

 д-р биол. наук, профессор, ведущий научный сотрудник, лаборатория популяционной генетики

 634050, Российская Федерация, Томск, наб. реки Ушайки, 10 

 Dr. Sci. (Biol.), Professor, Leading Research Scientist, Laboratory of Population Genetics 

 10, Nab. Ushaiki, Tomsk, 634050, Russian Federation 

aksana-kucher@medgenetics.ruhttps://orcid.org/0000-0003-1956-0692ШипулинВ. М.ShipulinV. M.

 д-р мед. наук, профессор, главный научный сотрудник

634012, Российская Федерация, Томск, ул. Киевская, 111а

 Dr. Sci. (Med.), Professor, Chief Research Scientist

 111a, Kievskaya str., Tomsk, 634012, Russian Federation 

shipulin@cardio-tomsk.ruНаучно-исследовательский институт медицинской генетики, Томский национальный исследовательский медицинский центр Российской академии наукРоссияResearch Institute of Medical Genetics, Tomsk National Research Medical Center, Russian Academy of SciencesRussian FederationНаучно-исследовательский институт кардиологии, Томский национальный исследовательский медицинский центр Российской академии наукРоссияCardiology Research Institute, Tomsk National Research Medical Center, Russian Academy of Sciences Russian Federation202104012022364125131Copyright © Бабушкина Н.П., Постригань А.Е., Кучер А.Н., Шипулин В.М., 20222022Бабушкина Н.П., Постригань А.Е., Кучер А.Н., Шипулин В.М.Babushkina N.P., Postrigan A.E., Kucher A.N., Shipulin V.M.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.sibjcem.ru/jour/article/view/1297

В современных популяциях система биотрансформации работает в условиях повышенной нагрузки, так как обеспечивает метаболизм не только широкого спектра эндогенных субстратов, но и различных ксенобиотиков, что может способствовать развитию заболеваний различных систем органов, а в ряде случаев приводить к формированию коморбидных состояний, при которых наблюдается усиленная работа системы метаболизма ксенобиотиков. В связи с этим большой интерес вызывает изучение вовлеченности полиморфизма генов метаболизма ксенобиотиков в формирование не только изолированной патологии, но и различных коморбидных состояний.Цель исследования: изучение вовлеченности полиморфного варианта rs4244285 гена CYP2C19, приводящего к синтезу нефункционального белка, в развитие как изолированной патологии, так и сочетанных заболеваний.Материал и методы. Изучена распространенность аллелей и генотипов rs4244285 в гене CYP2C19 в двух группах больных с коморбидными состояниями: ишемическая болезнь сердца с артериальной гипертензией (ИБС_АГ, n = 133); бронхиальная астма с гипертензией (БА_АГ, n = 178), в группе с изолированной патологией (БА, n = 135) и в популяционной выборке г. Томска (n = 377). Ассоциативный анализ проведен как в отношении исходных трех групп больных (ИБС, БА, БА_АГ), так и подгрупп, дифференцированных на основании наличия/отсутствия диагноза «артериальная гипертензия», сформированных с учетом анализа сопутствующих патологий как в выборках больных, так и в популяционном контроле.Результаты и обсуждение. Показан предрасполагающий, по сравнению с изолированной БА, эффект генотипа GA для развития сочетания БА с АГ (OR = 1,94; p = 0,038) и для сочетания ИБС с АГ (OR = 2,26; p = 0,009). Частота генотипа АА в 3,98 раза реже регистрировались в группе индивидов с АГ, чем с нормотензией, однако из-за низкой встречаемости данного генотипа различия не достигают уровня статистической значимости.Заключение. Полученные результаты могут быть объяснены участием CYP2C19-метаболитов арахидоновой кислоты в регуляции сосудистого тонуса, однако представленные данные требуют дальнейшего изучения.

Xenobiotic metabolism system in the current populations is involved in the biotransformation of a wide range of endogenous substrates and various xenobiotics, which can contribute to developing the diseases of various organ systems, and, in some cases, comorbid conditions where increased biotransformation system activity is observed. In this regard, it is of great interest to study the involvement of polymorphism in xenobiotic metabolism genes in the development of both isolated pathology and various comorbid conditions.Aim. The goal of study was to investigate the involvement of rs4244285 in the CYP2C19 gene in the development of isolated pathology and comorbidities.Material and Methods. The frequencies of alleles and genotypes were studied in groups of patients with comorbid conditions including groups of coronary artery disease (CAD) with hypertension (HTN) (CAD_HTN, n = 133) and bronchial asthma (BA) with HTN (BA_HTN, n = 178), in group of isolated BA (n = 135), and in the population sample of the city of Tomsk (n = 377). Association analysis covered three initial groups of patients (CAD, BA, and BA_HTN) and subgroups assigned based on the presence of absence of HTN diagnosis taking into account comorbid conditions both in patient samples and in population control.Results and Discussion. The study demonstrated the predisposing eff ect of GA genotype on the development of comorbid BA and HTN (OR = 1.94, p = 0.038) and comorbid CAD and HTN (OR = 2.26, p = 0.009) compared to isolated BA. The AA genotype was observed 3.98 times less often in HTN patients than in normotensive individuals. However, the diff erences did not reach the level of statistical signifi cance due to the low occurrence of this genotype.Conclusion. The obtained results may be explained by the involvement of CYP2C19-metabolites of arachidonic acid in the regulation of vascular tone, which requires further study.

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