AbstractDespite overall effort hypertensive disease (HD) is one of the most significant health and social problem. Essential hypertension is believed to be a multifactorial disease and polymorphism of genes that may be responsible for the regulation of blood pressure plays the key role in it. The least explored in this regard is single nucleotide polymorphism of ET-1 leading to the replacement of the amino acids of lysine (Lys) to asparagine (Asn) at position of 198th polypeptide chain (Lys198Asn).The objective of the research was to improve diagnosis of HD severity determining plasma concentration of ET-1, C-type natriuretic peptides (CNP) and the coefficient of CNP/ET-1 in patients with different genotypes of ET-1 gene.Materials and methods. The study involved 79 men without cardiovascular diseases (control group), 62 men with II stage HD and 50 men with HD complicated by chronic heart failure (CHF) II-III classes according to NYHA Classification. All patients were representative by age. Genotyping of ET-1 gene was conducted using polymerase chain reaction. ET-1 concentration in plasma was determined using ELISA method.Results. Lys/Lys genotype of ET-1 gene was found to occur in 65.82% of men in the control group, carriers of Asn allele (Lys/Asn and Asn/Asn genotypes) constituted 34.18%, Lys allele was observed in 79.75% of cases, Asn allele was detected in 20.25% of men. Among patients with II stage HD Lys/Lys genotype of ET-1 gene was observed in 56.45% of cases, the carriers of Asn allele (Lys/Asn and Asn/Asn genotypes) occurred in 43.55% of patients, Lys allele was found in 73.39% of cases, Asn allele was observed in 26.61% of patients. Among men with HD and CHF IIA genotype Lys/Lys was found in 66.00% of cases, carriers of Asn allele (Lys/Asn and Asn/Asn genotypes) was observed in 34.00% of patients, Lys allele was detected in 80.00% of cases, Asn allele was observed in 20.00% of cases. The men from the control group, patients with II stage HD and patients with HD and CHF as the carriers of Asn allele were found to have significantly higher plasma levels of ET-1 (2.53±0.12 fmol/ml, 13.90±0.22 fmol/ml and 14.07±0.18 fmol/ml, respectively) and CNP (2.98±0.08 pmol/ml, 5.90±0.11 pmol/ml and 5.93±0.18 pmol/ml, respectively) in comparison with homozygous carriers of Lys genotype (ET-1constituted 1.41±0.05 fmol/ml, 11.58±0.23 fmol/ml and 0.08±12.89 fmol/ml, respectively, CNP constituted 2.02±0.29 pmol/ml, 4.68±0.12 pmol/ml and 4.88±0.09 pmol/ml, respectively). According to the analysis of the obtained data, coefficient of CNP/ET-1 (0.40±0.003 c.u. and 0.38±0.006 c.u., respectively) and Asn allele (0.42±0.004 c.u. and 0.42±0.007 c.u., respectively) was significantly lower in patients with II stage HD and patients with HD and CHF as the carriers of Lys/Lys genotype in comparison with the control group (1.4±0.04 c.u. and 1.22±0.05 c.u., respectively). Carriers of Asn allele in the control group had significantly lower coefficient of CNP/ET-1 than genotype Lys/Lys carriers. However, the difference in the coefficient of CNP/ET-1 was not observed in patients with HD.Conclusions. Lys/Lys genotype and Lys allele of ET-1 gene were found to dominate among control group and patients with HD of different severity. Plasma concentration of ET-1, CNP were significantly higher and coefficient of CNP/ET-1 was lower in men with II stage HD and HD complicated by CHF than in men without cardiovascular diseases in case of all ET-1 gene genotypes. The carriers of Asn allele of ET-1 gene had significantly higher plasma levels of ET-1 and CNP in each study group.
Berezikova EN. Clinical and genetic and neurohormonal mechanisms of ischemic remodeling, myocardial apoptosis and heart failure: an innovative strategy of personalized diagnosis, prevention and treatment. PhD thesis. Federal State Institution Research Institute of Cardiology; 2014.
Voronkov LH, Amosova KM, Bahrii AE, et al. Recommendations for the diagnosis and treatment of chronic heart failure (2012). Kyiv; 2012.
Zarubina EG, Aseeva EV. The role of genetic predisposition in the development of cardiovascular disease in young adults with a violation of work and rest. Fundamentalnye issledovaniya. 2013; 11: 51-55.
Oleshko TB, Sviridenko DY, Harbuzova VY. Analysis of connection between Lys198Asn polymorphic variants of the endothelin-1 gene (EDN-1) with atherothrombotic ischemic stroke in individuals of different sex. Klinichna ta eksperymentalna patolohiia. 2016; 1(55): 99-103.
Kovalenko VM, Kornatsky VM. Cardiovascular diseases as medical and social and political problem. Kyiv; 2014.
Shcheglova EV. Clinical and prognostic value of polymorphism of some candidate genes and markers of endothelial dysfunction in patients who underwent acute coronary syndrome. PhD thesis. North Ossetian State Medical Academy; 2008.
Barden AE, Herbison CE, Beilin LJ, Michael CA, Walters BN, Van Bockxmeer FM. Association between the endothelin-1 gene Lys198Asn polymorphism blood pressure and plasma endothelin-1 levels in normal and pre-eclamptic pregnancy. J Hypertens. 2001; 19(10): 1775-82. http://dx.doi.org/10.1097/00004872-200110000-00011
Barаth А, Endreffy E, Bereczki Cs, Gellen B, Szucs B, Nemeth I, Turi S. Endothelin-1 gene and endothelial nitric oxidesynthase gene polymorphisms in adolescentswith juvenile and obesity-associatedhypertension. Acta Physiologica Hungarica. 2007; 94(1-2): 49-66.
Dzholdasbekova AU, Gaipov AE. The association between polymorphism of Lys198Asn of endothelin-1 gene and arterial hypertension risk in Kazakh people. Eur J Gen Med. 2010; 7(2): 187-191.
Jing JJ, Jun N, Zhihong W, Yamamoto M, Abe M, Tabara Y, et al. Association of endothelin-1 gene variant with hypertension. Hypertension. 2003;41: 163-167. http://dx.doi.org/10.1161/01.HYP.0000043680.75107.CF
Senol S, Akar I, Kargün K, Bayram A, Kara M and Secen Ö. Endothelin-1 gene polymorphism in preoperative myocardial infarction with/or without coronary artery bypass graft. Int J Hum Genet. 2014; 14 (3,4): 183-187.
Tanaka С, Kamide K, Takiuchi S, Kawano Y, Miyata T. Evaluation of the Lys198Asn and 134delA genetic polymorphisms of the endothelin-1 gene. Hypertens Res. 2004; 27: 367–371. http://dx.doi.org/10.1291/hypres.27.367
Tiret L, Poirier O, Hallet V, McDonagh TA, Morrison C, et al. The Lys198Asn polymorphism in the endothelin-1 gene is associated with blood pressure in overweight people. Hypertension. 1999; 33: 1169-1174. http://dx.doi.org/10.1161/01.HYP.33.5.1169
Treiber FA, Barbeau P, Harshfield G, Kang H-S, Pollock DM, Pollock JS, et al. Endothelin-1 Gene LYS198ASN Polymorphism and Blood Pressure Reactivity. Hypertension. 2003 Oct 1;42(4):494–499. http://doi.org/10.1161/01.HYP.0000091266.41333.15
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.