Clinical significance of single nucleotide missense-mutation rs950880 of the IL1RL1 gene in patients with essential hypertension
Modern cardiology requires the search for specific pathogenetically involved gene mutations, the consequences of which can be considered in the management of patients with hypertension. Scientists are targeting C/A polymorphism at the rs950880 position, which is associated with tissue expression of the IL1RL1 gene and the plasma level of soluble ST2 – a new biomarker in the diagnosis of cardiovascular disease. The aim of the study was to evaluate the association of rs950880 polymorphism of the IL1RL1 gene and the state of central and intracardiac hemodynamics in men with essential hypertension (EН) of varying severity, residents of the Podillia region of Ukraine. 170 men who met the inclusion criteria were examined according to a standard protocol, which included clinical, laboratory and instrumental examinations in accordance with current recommendations. The subjects were divided into a control group of 70 men without cardiovascular disease and a study group of 50 men with asymptomatic EН and 50 people with EH complicated by IIA stage chronic heart failure (CHF). Genotyping of SNP rs950880 of the IL1RL1 gene was performed using an allele-specific polymerase chain reaction. All men in the control group and the study group underwent echocardiography with Doppler according to the standard protocol. Statistical processing of the obtained results was performed in the package Statistica 12.0 using conjugation tables analysis, analysis of variance. It was found that among men living in Vinnytsia, Ukraine, carriers of СС and CA SNP rs950880 of the IL1RL1 gene dominate (42.35 % and 45.30 % of individuals, respectively), AA homozygotes are significantly less common (12.53 %, p<0.05). Men without cardiovascular diseases and patients with EH do not differ significantly in the frequency of different variants of the genotype of the studied gene. C\A polymorphism is not associated with the risk of EН. The homozygotes AA with EH have a significantly lower LV myocardial mass index (LVMMI) (69.14±6.90 g/m2.7, compared with homozygotes CC – 75.42±2.54 g/m2.7, and heterozygotes CA – 76.96±3.18 g/m2.7, p<0.05). Among the carriers of the C allele, an "unfavorable" EН phenotype is mainly formed in the form of a high risk of LV hypertrophy (OR=11.36, 95 % СI=0.63-24.76, χ2=14.32, p=0.0008). Homozygotes AA in the rs950880 locus of the IL1RL1 gene, on the contrary, have a low probability of developing LV hypertrophy (OR=0.80, 95 % SI=0.02-0.42, χ2=14.32, p=0.0008) and its preserved systolic function. Thus, the SNP rs950880 of the IL1RL1 gene is not associated with the risk of EH or its severity in residents of Vinnytsia, Ukraine. Carriage of the C allele is accompanied by the formation of an "unfavorable" EH phenotype with a significantly high risk of LV hypertrophy.
 Aimo, A., Maisel, A. S., Castiglione, V., & Emdin, M. (2019). sST2 for outcome prediction in acute heart failure: which is the best cutoff?. Journal of the American College of Cardiology, 74(3), 478-479. doi: 0.1016/j.jacc.2019.03.527
 Aleksova, A., Paldino, A., Beltrami, A. P., Padoan, L., Iacoviello, M., Sinagra, G., ... & Maisel, A. S. (2019). Cardiac biomarkers in the emergency department: the role of soluble ST2 (sST2) in acute heart failure and acute coronary syndrome – there is meat on the bone. Journal of clinical medicine, 8(2), 270-279. doi: 10.3390/jcm8020270
 Baba, Y., Maeda, K., Yashiro, T., Inage, E., Kasakura, K., Suzuki, R., ... & Nishiyama, C. (2012). GATA2 is a critical transactivator for the human IL1RL1/ST2 promoter in mast cells/basophils: opposing roles for GATA2 and GATA1 in human IL1RL1/ST2 gene expression. Journal of Biological Chemistry, 287(39), 32689-32696. https://doi.org/10.1074/jbc.M112.374876
 Bahrij, D. A., Starzhynska, O. L., & Zhebel, V. M. (2020). Концентрація розчинного ST2 у плазмі крові та дисфункція серця в пацієнтів з есенціальною гіпертензією [Concentration of soluble ST2 and heart dysfunction in hypertensive patients]. Український кардіологічний журнал – Ukrainian Journal of Cardiology, 27(5), 53-59. doi: 10.31928/1608-635X-2020.5.5359
 Bi, J., Garg, V., & Yates, A. R. (2021). Galectin-3 and sST2 as Prognosticators for Heart Failure Requiring Extracorporeal Life Support: Jack n’Jill. Biomolecules, 11(2), 166. doi: 10.3390/biom11020166
 Evangelou, E., Warren, H. R., Mosen-Ansorena, D., Mifsud, B., Pazoki, R., Gao, H., ... & Lind, L. (2018). Genetic analysis of over 1 million people identifies 535 new loci associated with blood pressure traits. Nature genetics, 50(10), 1412-1425. doi: 10.1038/s41588-018-0205-x
 Farcaş, A. D., Anton, F. P., Goidescu, C. M., Gavrilă, I. L., Vida-Simiti, L. A., & Stoia, M. A. (2017). Serum soluble ST2 and diastolic dysfunction in hypertensive patients. Disease markers, (5), 1-8. doi: 10.1155/2017/2714095
 Ho, J. E., Chen, W. Y., Chen, M. H., Larson, M. G., McCabe, E. L., Cheng, S., ... & Wang, T. J. (2013). Common genetic variation at the IL1RL1 locus regulates IL-33/ST2 signaling. The Journal of clinical investigation, 123(10), 4208-4218. doi: 10.1172/JCI67119
 Johansson, Å., Rask-Andersen, M., Karlsson, T., & Ek, W. E. (2019). Genome-wide association analysis of 350 000 Caucasians from the UK Biobank identifies novel loci for asthma, hay fever and eczema. Human molecular genetics, 28(23), 4022-4041. doi: 10.1093/hmg/ddz175
 Lin, J. F., Wu, S., Juang, J. M. J., Chiang, F. T., Hsu, L. A., Teng, M. S., ... & Ko, Y. L. (2017). IL1RL1 single nucleotide polymorphism predicts sST2 level and mortality in coronary and peripheral artery disease. Atherosclerosis, 257(2), 71-77. doi: 10.1016/j.atherosclerosis.2016.12.020
 Maupoint, J., Richard, V., Vallet, C., Albrecht, C., Ouchani, F., Eltchaninoff, H., & Bauer, F. (2016, August). Correlation between ST2 levels, Doppler echocardiographic parameters and prognosis in patients with heart failure and preserved ejection fraction. In European heart journal (Vol. 37, pp. 716-716). Great Clarendon St, Oxford OX2 6DP, England: Oxford Univ Press.
 Nagueh, S. F., Smiseth, O. A., Appleton, C. P., Byrd, B. F., Dokainish, H., Edvardsen, T., ... & Houston, Texas; Oslo, Norway; Phoenix, Arizona; Nashville, Tennessee; Hamilton, Ontario, Canada; Uppsala, Sweden; Ghent and Liège, Belgium; Cleveland, Ohio; Novara, Italy; Rochester, Minnesota; Bucharest, Romania; and St. Louis, Missouri. (2016). Recommendations for the evaluation of left ventricular diastolic function by echocardiography: an update from the American Society of Echocardiography and the European Association of Cardiovascular Imaging. European Journal of Echocardiography, 17(12), 1321-1360. doi: 10.1016/j.echo.2016.01.011
 Schmitz, J., Owyang, A., Oldham, E., Song, Y., Murphy, E., McClanahan, T. K., ... & Kastelein, R. A. (2005). IL-33, an interleukin-1-like cytokine that signals via the IL-1 receptor-related protein ST2 and induces T helper type 2-associated cytokines. Immunity, 23(5), 479-490. doi: 10.1016/j.immuni.2005.09.015
 Whelton, P. K., Carey, R. M., Aronow, W. S., Casey, D. E., Collins, K. J., Dennison Himmelfarb, C., ... & Wright, J. T. (2018). 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA guideline for the prevention, detection, evaluation, and management of high blood pressure in adults: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Journal of the American College of Cardiology, 71(19), e127-e248. doi: 10.1161/HYP.0000000000000065
This work is licensed under a Creative Commons Attribution 4.0 International License.