The relationship of the carriership of allelic variations in rs2228145 (A > C) of the<i>IL6R</i> gene with the levels of <i>VCAM1</i> and <i>ICAM1</i> gene transcripts in patients with essential hypertension

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 IL6...

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Main Authors: L. V. Topchieva, V. A. Korneva, I. V. Kurbatova
Format: Article
Language:English
Published: Siberian Branch of the Russian Academy of Sciences, Federal Research Center Institute of Cytology and Genetics, The Vavilov Society of Geneticists and Breeders 2020-03-01
Series:Вавиловский журнал генетики и селекции
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Online Access:https://vavilov.elpub.ru/jour/article/view/2485
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author L. V. Topchieva
V. A. Korneva
I. V. Kurbatova
author_facet L. V. Topchieva
V. A. Korneva
I. V. Kurbatova
author_sort L. V. Topchieva
collection DOAJ
description 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 &gt; 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 &gt; 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 &gt; 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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spelling doaj-art-9a49eab5a1b642ad9ad83db76fc9901b2025-02-01T09:58:08ZengSiberian Branch of the Russian Academy of Sciences, Federal Research Center Institute of Cytology and Genetics, The Vavilov Society of Geneticists and BreedersВавиловский журнал генетики и селекции2500-32592020-03-012419610110.18699/VJ20.6001027The relationship of the carriership of allelic variations in rs2228145 (A > C) of the<i>IL6R</i> gene with the levels of <i>VCAM1</i> and <i>ICAM1</i> gene transcripts in patients with essential hypertensionL. V. Topchieva0V. A. Korneva1I. V. Kurbatova2Institute of Biology of the Karelian Research Centre, Russian Academy of SciencesPetrozavodsk State UniversityInstitute of Biology of the Karelian Research Centre, Russian Academy of SciencesThe 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 &gt; 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 &gt; 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 &gt; C) genotype on the transcriptional activity of ICAM1, which argues for its role in the pathogenesis of endothelial dysfunction and essential hypertension.https://vavilov.elpub.ru/jour/article/view/2485interleukin 6il6r geneessential arterial hypertensionendothelial dysfunction
spellingShingle L. V. Topchieva
V. A. Korneva
I. V. Kurbatova
The relationship of the carriership of allelic variations in rs2228145 (A > C) of the<i>IL6R</i> gene with the levels of <i>VCAM1</i> and <i>ICAM1</i> gene transcripts in patients with essential hypertension
Вавиловский журнал генетики и селекции
interleukin 6
il6r gene
essential arterial hypertension
endothelial dysfunction
title The relationship of the carriership of allelic variations in rs2228145 (A > C) of the<i>IL6R</i> gene with the levels of <i>VCAM1</i> and <i>ICAM1</i> gene transcripts in patients with essential hypertension
title_full The relationship of the carriership of allelic variations in rs2228145 (A > C) of the<i>IL6R</i> gene with the levels of <i>VCAM1</i> and <i>ICAM1</i> gene transcripts in patients with essential hypertension
title_fullStr The relationship of the carriership of allelic variations in rs2228145 (A > C) of the<i>IL6R</i> gene with the levels of <i>VCAM1</i> and <i>ICAM1</i> gene transcripts in patients with essential hypertension
title_full_unstemmed The relationship of the carriership of allelic variations in rs2228145 (A > C) of the<i>IL6R</i> gene with the levels of <i>VCAM1</i> and <i>ICAM1</i> gene transcripts in patients with essential hypertension
title_short The relationship of the carriership of allelic variations in rs2228145 (A > C) of the<i>IL6R</i> gene with the levels of <i>VCAM1</i> and <i>ICAM1</i> gene transcripts in patients with essential hypertension
title_sort relationship of the carriership of allelic variations in rs2228145 a c of the i il6r i gene with the levels of i vcam1 i and i icam1 i gene transcripts in patients with essential hypertension
topic interleukin 6
il6r gene
essential arterial hypertension
endothelial dysfunction
url https://vavilov.elpub.ru/jour/article/view/2485
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