vavilovВавиловский журнал генетики и селекцииVavilov Journal of Genetics and Breeding2500-3259Institute of Cytology and Genetics of Siberian Branch of the RAS10.18699/VJ20.600vavilov-2485Research ArticleМЕДИЦИНСКАЯ ГЕНЕТИКАMEDICAL GENETICSСвязь носительства аллельных вариаций по rs2228145 (A > C) гена IL6R c уровнем транскриптов генов VCAM1 и ICAM1 при эссенциальной артериальной гипертензииThe relationship of the carriership of allelic variations in rs2228145 (A > C) of theIL6R gene with the levels of VCAM1 and ICAM1 gene transcripts in patients with essential hypertensionhttps://orcid.org/0000-0001-8697-2086ТопчиеваЛ. В.TopchievaL. V.

Петрозаводск

Petrozavodsk

topchieva67@mail.ruhttps://orcid.org/0000-0003-2231-4695КорневаВ. А.KornevaV. A.https://orcid.org/0000-0001-7620-7065КурбатоваИ. В.KurbatovaI. V.

Петрозаводск

Petrozavodsk

Институт биологии - обособленное подразделение Федерального исследовательского центра Карельский научный центр, Российская академия наукРоссияInstitute of Biology of the Karelian Research Centre, Russian Academy of SciencesRussian FederationПетрозаводский государственный университетРоссияPetrozavodsk State UniversityRussian Federation20201803202024196101Copyright © Топчиева Л.В., Корнева В.А., Курбатова И.В., 20202020Топчиева Л.В., Корнева В.А., Курбатова И.В.Topchieva L.V., Korneva V.A., Kurbatova I.V.This work is licensed under a Creative Commons Attribution 4.0 License.https://vavilov.elpub.ru/jour/article/view/2485

При сердечно-сосудистых заболеваниях в плазме крови наблюдается повышение содержания интерлейкина 6 и его растворимых рецепторов, что указывает на усиление IL-6/sIL-6R сигнала в клетках и развитие хронического воспаления. Носительство аллельных вариаций по rs2228145 гена IL6R ассоциировано с изменением содержания растворимой и мембраносвязанной форм рецептора, опосредующих биологическую активность самого цитокина. IL-6 участвует в развитии эндотелиальной дисфункции посредством регуляции экспрессии генов VCAM1 и ICAM1, кодирующих молекулы межклеточной адгезии. До настоящей работы данные об ассоциации эссенциальной артериальной гипертензии (ЭАГ) с аллельными вариациями по rs2228145 гена IL6R не были представлены.

Цель исследования - изучить связь носительства аллельных вариаций по rs2228145 (A > C) с развитием ЭАГ и уровнем транскриптов генов VCAM1, ICAM1. Для этого нами использованы образцы ДНК, выделенной из цельной крови здоровых доноров (148) и пациентов с ЭАГ (I-II стадии) (152). Генотипирование проводили методом ПЦР-ПДРФ. Уровень транскриптов в лейкоцитах периферической крови оценивали с помощью ПЦР в режиме реального времени. Обнаружены различия в распределении частот генотипов по rs2228145 (A > C) в контрольной группе и группе пациентов с ЭАГ (χ2 = 9.303). Частота генотипа СС в группе больных людей оказалась выше, чем в группе здоровых (0.191 и 0.095 соответственно). Выявлено, что у носителей генотипа СС риск развития ЭАГ (I-II стадии) в 2.3 раза выше (ОШ = 2.257, 95 % доверительный интервал 1.100-4.468), чем у лиц, имеющих альтернативные генотипы. Уровень транскриптов генов VCAM1, ICAM1 значимо выше в лейкоцитах периферической крови больных ЭАГ, чем здоровых людей. Содержание транскриптов гена ICAM1 оказалось в 4 раза выше у больных ЭАГ с генотипом СС. С помощью дисперсионного анализа Крускела-Уоллиса определено влияние на транскрипционную активность указанного гена генотипа по rs2228145 (A > C), что говорит о его роли в патогенезе эндотелиальной дисфункции и эссенциальной артериальной гипертензии.

The levels of plasma interleukin 6 and its soluble receptors were found to be elevated in subjects with cardiovascular diseases, which points to amplification of the IL-6-mediated trans-signaling pathway in cells and the development of chronic inflammation. The allelic variation in the rs2228145 IL6R gene is associated with a change in the contents of the soluble and membrane-bound receptor forms mediating the biological activity of IL-6. Cytokine IL-6 is involved in the development of endothelial dysfunction by regulating the expression of the VCAM1 and ICAM1 genes, encoding intercellular adhesion molecules. Prior to this work, no data on the association of essential arterial hypertension (EAH) with rs2228145 allelic variations of the IL6R gene have been reported.

The aim of our work was to study the relationship of the carriership of rs2228145 (A > C) allelic variations with the development of EAH and the VCAM1 and ICAM1 transcript levels. We analyzed samples of DNA isolated from the whole blood of 148 healthy donors and 152 patients with EAH (stages I-II). The genotyp-ing was performed by PCR-RFLP. The level of transcripts in peripheral blood leukocytes (PBL) was assessed by real-time PCR. Differences in the frequency distributions of rs2228145 (A > C) genotypes between the control group and the group of patients with EAH (χ2 = 9.303) were found. The frequency of the CC genotype in EAH patients was higher than in healthy people (0.191 and 0.095, respectively). The risk of EAH (I-II stages) development was shown to be 2.3 times higher in CC genotype carriers as compared to individuals with other genotypes (OR = 2.257, 95 % confidence interval 1.100-4.468). The levels of VCAM1 and ICAM1 gene transcripts in PBL of patients with EAH were significantly higher than in healthy people. The level of ICAM1 gene transcripts was almost 4 times higher in patients with CC genotype. The Kruskal-Wallis analysis of variance revealed an effect of rs2228145 (A > C) genotype on the transcriptional activity of ICAM1, which argues for its role in the pathogenesis of endothelial dysfunction and essential hypertension.

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