2658-6533Research Results in Biomedicine2658-653310.18413/2658-6533-2023-9-1-0-42984Genetics<strong>Allelic polymorphism of genes involved in <em>IL-1</em></strong><strong><em>&beta;</em></strong><strong> production and predisposition of people to the development of arterial hypertension</strong><strong>Allelic polymorphism of genes involved in <em>IL-1</em></strong><strong><em>&beta;</em></strong><strong> production and predisposition of people to the development of arterial hypertension</strong>TopchievaLudmila V.TopchievaLudmila V.topchieva67@mail.ruKurbatovaIrina V.KurbatovaIrina V.irina7m@yandex.ruMalyshevaIrina E.MalyshevaIrina E.i.e.malysheva@yandex.ruKornevaViktoria A.KornevaViktoria A.vikkorneva@mail.ruTopchievaAnna V.TopchievaAnna V.topchiev98@mail.ru20239100

Background: The level of IL-1&beta; in blood plasma is determined not only by pro-inflammatory stimuli, but also by allelic polymorphism of the IL1B and NLRP3 genes. Information on the association of allelic polymorphism of these genes with the risk of arterial hypertension (AH) is scarce and contradictory. The aim of the study: To assess the risk of developing hypertension in carriers of various allelic variants according to the polymorphic markers rs1143634 (c.3953C&gt;T), rs16944 (c.-511T&gt;C), rs1143627 (c.-31C&gt;T) of the IL1B gene and rs35829419 (c.2113C&gt;A) of the NLRP3 gene, as well as to study possible mechanisms for the inclusion of allelic polymorphism of these genes in the etiology and pathogenesis of AH. Materials and methods: 182 DNA samples from healthy people and 180 DNA samples from patients with hypertension (stages I-II) were used for genotyping rs1143634, rs16944, rs1143627 (PCR-RFLP analysis). 215 DNA samples from healthy individuals and 180 hypertensive patients were used to determine alleles and genotypes for rs35829419 of the NLRP3 gene (allele-specific PCR with TaqMan probes). Total RNA obtained from peripheral blood leukocytes (PBL) of 45 healthy people and 50 patients with AH (27 people taking metoprolol or bisoprolol for more than a year and 23 people without antihypertensive therapy) for assessment of gene expression by real-time PCR was used. The content of pro-inflammatory proteins in the blood plasma of 40 healthy individuals was measured by ELISA. Results: Carriers of the TT genotype for the c.3953C&gt;T marker of the IL1B gene were found to have a 3-fold increased risk of AH (OR=3,239; 95% CI: 1,858-5,649). In healthy individuals with this genotype, the content of IL-1&beta; in blood plasma and the expression of the ICAM1 gene in PBL are higher than in heterozygotes or homozygotes for the C allele (p=0,029 and p=0,004, respectively). Individuals with the TT genotype for the c.-31C&gt;T marker of the IL1B gene had a reduced risk of АН (OR=0,645; 95% CI: 0,481-0,866). IL1B gene expression and hsCRP levels were lower in healthy individuals with the T allele for rs1143627 (p=0,022, p=0,040, respectively). There were no differences in the distribution of allele and genotype frequencies for markers c.-511T&gt;C of the IL1B gene and c.2113C&gt;A of the NLRP3 gene in the studied groups. Conclusion: Polymorphic markers rs1143634 (c.3953C&gt;T) and rs1143627 (c.-31C&gt;T) of the IL1B gene are probably involved in the predisposition of the inhabitants of Karelia to the development of arterial hypertension

Background: The level of IL-1&beta; in blood plasma is determined not only by pro-inflammatory stimuli, but also by allelic polymorphism of the IL1B and NLRP3 genes. Information on the association of allelic polymorphism of these genes with the risk of arterial hypertension (AH) is scarce and contradictory. The aim of the study: To assess the risk of developing hypertension in carriers of various allelic variants according to the polymorphic markers rs1143634 (c.3953C&gt;T), rs16944 (c.-511T&gt;C), rs1143627 (c.-31C&gt;T) of the IL1B gene and rs35829419 (c.2113C&gt;A) of the NLRP3 gene, as well as to study possible mechanisms for the inclusion of allelic polymorphism of these genes in the etiology and pathogenesis of AH. Materials and methods: 182 DNA samples from healthy people and 180 DNA samples from patients with hypertension (stages I-II) were used for genotyping rs1143634, rs16944, rs1143627 (PCR-RFLP analysis). 215 DNA samples from healthy individuals and 180 hypertensive patients were used to determine alleles and genotypes for rs35829419 of the NLRP3 gene (allele-specific PCR with TaqMan probes). Total RNA obtained from peripheral blood leukocytes (PBL) of 45 healthy people and 50 patients with AH (27 people taking metoprolol or bisoprolol for more than a year and 23 people without antihypertensive therapy) for assessment of gene expression by real-time PCR was used. The content of pro-inflammatory proteins in the blood plasma of 40 healthy individuals was measured by ELISA. Results: Carriers of the TT genotype for the c.3953C&gt;T marker of the IL1B gene were found to have a 3-fold increased risk of AH (OR=3,239; 95% CI: 1,858-5,649). In healthy individuals with this genotype, the content of IL-1&beta; in blood plasma and the expression of the ICAM1 gene in PBL are higher than in heterozygotes or homozygotes for the C allele (p=0,029 and p=0,004, respectively). Individuals with the TT genotype for the c.-31C&gt;T marker of the IL1B gene had a reduced risk of АН (OR=0,645; 95% CI: 0,481-0,866). IL1B gene expression and hsCRP levels were lower in healthy individuals with the T allele for rs1143627 (p=0,022, p=0,040, respectively). There were no differences in the distribution of allele and genotype frequencies for markers c.-511T&gt;C of the IL1B gene and c.2113C&gt;A of the NLRP3 gene in the studied groups. Conclusion: Polymorphic markers rs1143634 (c.3953C&gt;T) and rs1143627 (c.-31C&gt;T) of the IL1B gene are probably involved in the predisposition of the inhabitants of Karelia to the development of arterial hypertension

allelic polymorphism of genesinterleukin 1 betaIL1B genearterial hypertensionallelic polymorphism of genesinterleukin 1 betaIL1B genearterial hypertensionСписок литературыTanase DM, Gosav EM, Radu S, et al. Arterial Hypertension and Interleukins: Potential Therapeutic Target or Future Diagnostic Marker? International Journal of Hypertension. 2019;2019:3159283. DOI: https://doi.org/10.1155/2019/3159283Pfeiler S, Winkels H, Kelm M, et al. IL-1 family cytokines in cardiovascular disease. Cytokine. 2019;122:154215. DOI: https://doi.org/10.1016/j.cyto.2017.11.009De Miguel C, Pelegr&iacute;n P, Baroja-Mazo A, et al. Emerging Role of the Inflammasome and Pyroptosis in Hypertension. International Journal of Molecular Sciences. 2021;22(3):1064. DOI: https://doi.org/10.3390/ijms22031064Oliveirа A, Dinis-Oliveira RJ, Nogueira A, et al. Interleukin-1&beta; genotype and circulating levels in cancer patients: Metastatic status and pain perception. Clinical Biochemistry. 2014;47(13-14):1209-1213. &nbsp;DOI: https://doi.org/10.1016/j.clinbiochem.2014.04.009Wu JF, Song SH, Lee CS, et al. Clinical predictors of liver fibrosis in patients with chronic hepatitis virus infection from children to adults. Journal of Infectious Diseases. 2018;217(9):1408-1416. DOI: https://doi.org/10.1093/infdis/jiy048Ponce-Gallegos MA, Ramos-Mart&iacute;nez E, Garc&iacute;a-Carmona A, et al. Genetic susceptibility to antisynthetase syndrome associated with single-nucleotide variants in the IL1B gene that lead variation in IL-1b serum levels. Frontiers in Medicine. 2020;7:547186. DOI: https://doi.org/10.3389/fmed.2020.547186Wang X, Jiang F, Liang Y, et al. Interleukin-1b-31C/T and -511T/C Polymorphisms Were Associated with Preeclampsia in Chinese Han Population. PLoS ONE. 2014;9(9):e106919. DOI:&nbsp;https://doi.org/10.1371/journal.pone.0106919Pociot F, Molvig J, Wogensen L, et al. A TaqI polymorphism in the human interleukin-1 beta (IL-1 beta) gene correlates with IL-1 beta secretion in vitro. European Journal of Clinical Investigation. 1992;22(6):396-402. DOI: https://doi.org/10.1111/j.1365-2362.1992.tb01480.xPani P, Tsilioni I, McGlennen R, et al. IL-1B (3954) polymorphism and red complex bacteria increase IL-1&beta; (GCF) levels in periodotitis. Journal Periodontal Research. 2021;56(3):501-511. DOI: https://doi.org/10.1111/jre.12850Verma D, S&auml;rndahl E, Andersson H, et al. The Q705K Polymorphism in NLRP3 Is a Gain-of-Function Alteration Leading to Excessive Interleukin-1b and IL-18 Production. PLoS ONE. 2012;7(4):e34977. DOI: https://doi.org/10.1371/journal.pone.0034977Timasheva YR, Nasibullin TR, Imaeva EB, et al. Polymorphisms of inflammatory markes and risk of essential hypertension in Tatars from Russia. Clinical and Experimental Hypertension. 2015;37(5):398-403. DOI: https://doi.org/10.3109/10641963.2014.987394Shamonina TI, Radaeva OA, Novikova LV. Polymorphism of genes of IL-1&beta; in arterial hypertension in patients with metabolic syndrome. Fundamental&#39;nyye issledovaniya. 2014;10:1195-1198. Russian.Huang G, Niu T, Peng S, et al. Association between the interleukin-1B C-511T polymorphism and blood pressure in a Chinese hypertensive population. Immunology Letters. 2004;91(2-3):159-162. DOI: https://doi.org/10.1016/j.imlet.2003.11.009Yanagisawa A, Suzuki K, Kimura A, et al. Possible protective effect of serum b-carotene levels on the association between interleukin-1B C-31T polymorphism and hypertension in a Japanese population. Clinical Nutrition. 2009;28(2):198-202. DOI: https://doi.org/10.1016/j.clnu.2009.01.020Goracy J, Goracy I, Safranow K, et al. Lack of Association of Interleukin-1 Gene Cluster Polymorphisms with Angiographically Documented Coronary Artery Disease: Demonstration of Association with Hypertension in the Polish Population. Archives of Medical Research. 2011;42(5):426-432. DOI: https://doi.org/10.1016/j.arcmed.2011.08.002Lin RCY, Morris BJ. Association analysis of polymorphisms at the interleukin-1 locus in essential hypertension. American Journal of Medical Genetics. 2002;107(4):311-316. DOI: https://doi.org/10.1002/ajmg.10177Conen D, Cheng S, Steiner LL, et al. Association of 77 Polymorphisms in 52 Candidate Genes with Blood Pressure Progression and Incident Hypertension: The Women&rsquo;s Genome Health Study. Journal of Hypertension. 2009;27(3):476-483. DOI: https://doi.org/10.1097/hjh.0b013e32832104c8Williams B, Mancia G, Spiering W, et al. 2018 Practice Guidelines for the management of arterial hypertension of the European Society of Cardiology and the European Society of Hypertension. Blood Pressure. 2018;27(6):314-340. DOI: https://doi.org/10.1080/08037051.2018.1527177Zhang G, Zhou B, Li S, et al. Allele-specific induction of IL-1&beta; expression by C/EBP&beta; and PU.1 contributes to increased tuberculosis susceptibility. PLoS Pathogens. 2014;10(10):e1004426. DOI: https://doi.org/10.1371/journal.ppat.1004426Hameed I, Masood SR, Malik PA, et al. Genetic variations in key inflammatory cytokines exacerbates the risk of diabetic nephropathy by influencing the gene expression. Gene. 2018;661:51-59. DOI: https://doi.org/10.1016/j.gene.2018.03.095Shete AR, Joseph R, Vijayan NN, et al. Association of single nucleotide gene polymorphism at Interleukin-1b +3954, -511, and -31 in chronic periodontitis and aggressive periodontitis in dravidian ethnicity. Journal Periodontology. 2010;81(1):62-69. DOI: https://doi.org/10.1902/jop.2009.090256de Fraia Pinto L, Compri CM, Fornari JV, et al. The immunosuppressant drug, thalidomide, improves hepatic alterations induced by a high-fat diet in mice. Liver International. 2010;30(4):603-610. DOI: https://doi.org/10.1111/j.1478-3231.2009.02200.xRajan S, Ye J, Bai S, et al. NF-kappaB, but not p38 MAP kinase, is required for TNF-alpha-induced expression of cell adhesion molecules in endothelial cells. Journal of Cellular Biochemistry. 2008;105(2):477-486.&nbsp;DOI:&nbsp;https://doi.org/10.1002/jcb.21845Trott DW, Harrison DG. The immune system in hypertension. American Journal of Physiology - Advances in Physiology Education. 2014;38(1):20-24. DOI:&nbsp;https://doi.org/10.1152/advan.00063.2013Zhu J, Yang Y, Hu SG, et al. T-lymphocyte Kv1.3 channel activation triggers the NLRP3 inflammasome signaling pathway in hypertensive patients. Experimental and Therapeutic Medicine. 2017;14(1):147-154. DOI:&nbsp;https://doi.org/10.3892/etm.2017.4490Liu D, Zeng X, Li X, et al. Role of NLRP3 inflammasome in the pathogenesis of cardiovascular diseases. Basic Research in Cardiology. 2018;113:5. DOI:&nbsp;https://doi.org/10.1007/s00395-017-0663-9Sun HJ, Ren XS, Xiong XQ, et al. NLRP3 inflammasome activation contributes to VSMS phenotypic transformation and proliferation in hypertension. Cell Death and Disease. 2017;8(10):e3074. DOI:&nbsp;https://doi.org/10.1038/cddis.2017.470Yamamoto Y, Ikeda K, Watanabe M, et al. Expression of adhesion molecules in cultured human nasal mucosal microvascular endothelial cells activated by interleukin-1 beta or tumor necrosis factor-alpha: effects of dexamethasone. International Archives of Allergy and Immunology. 1998;117(1):68-77. DOI:&nbsp;https://doi.org/10.1159/000023992Koushki K, Shahbaz SK, Mashayekhi K, et al. Anti-inflammatory action of statins in cardiovascular disease: the role of inflammasome and toll-like receptor pathways. Clinical Reviews in Allergy and Immunology. 2021;60(2):175-199. DOI:&nbsp;https://doi.org/10.1007/s12016-020-08791-9Mendon&ccedil;a SA, Teixeira FG, Oliveira KM, et al. Stady of the association between the interleukin-1&beta; c3954C&gt;T polymorphism and periodontitis in a population sample from Bahia, Braxil. Contemporary Clinical Dentistry. 2015;6(2):176-182. DOI:&nbsp;https://doi.org/10.410310976-237x.156040B&eacute;guin E.P, van den Eshof BL, Hoogendijk AS, et al. Integrated proteomic analysis of tumor necrosis factor &alpha; and interleukin 1&beta;-induced endothelial inflammation. Journal of. Proteomics. 2019;192:89-101. DOI:&nbsp;https://doi.org/10.1016/j.jprot.2018.08.011Bai B, Yang Y, Wang QI, et al. NLRP3 Inflammasome in endothelial dysfunction. Cell Death and Disease. 2020;11:776. DOI:&nbsp;https://doi.org/10.1038/341419-020-02985-xKluger MS. Vascular endothelial cell adhesion and signaling during leukocyte recruitment. Advances in Dermatology. 2004;20:163-201.Gao H, Zhang Q, Chen J, et al. Porcine Il-6, IL-1&beta;, and TNF-&alpha; regulate the expression of pro-inflammatory-related genes and tissue factor in human umbilical vein endothelial cells. Xenotransplantation. 2018;25(5):e12408. DOI https://doi.org/10.1111/xen.12408