Shkarupa V. M., Sierkova V. K., Lilevska А. А.

MEDICAL GENETICS

Scentific article

Chronic obstructive pulmonary disease (COPD) is one of the main problems of theoretical and practical medicine among the diseases of the internal organs. COPD is associated with the high prevalence, nonstop progression and shortening life expectancy of patients. Despite the leading role of environmental factors in the pathogenesis of this pathology, the genetic predisposition to COPD is considered by many researchers to be convincing. Singlenucleotide polymorphisms of the endothelin-1 gene EDN1 are considered as possible genetic markers of endothelial dysfunction. Numerous studies have shown the important role of endothelin-1 in the development of COPD. However, there are only isolated reports of an analysis of the association of EDN1 gene polymorphism with the risk of COPD. The aim of the study was to determine the frequencies of alleles and genotypes of ONP Lys198Asn gene EDN1 in men of Podilsky region of Ukraine with COPD. Object and methods. Genotyping by single nucleotide polymorphisms LYS198ASN of the EDN1 gene was performed in 84 COPD patients (38 had a combination of COPD with coronary heart disease) in men aged 36-70 years, with an average age of 56.4 ± 3.8 years and 50 healthy men by PCR-RT. Results. It was found that the frequencies of the variant allele in the control group and in men with COPD were 0.14 and 0.23, respectively and were not statistically different (p = 0,07). In the COPD group, unlike the control group, genotype distribution was different from the Hardy-Weinberg law (p = 0,03). No significant differences were found in the distribution of genotypes between patients with COPD and controls in the additive, recessive, and dominant models of inheritance. Conclusions. The absence of association of single nucleotide Lys198Asn polymorphisms of the EDN1 gene with the risk of developing COPD in men of Podilskyi region of Ukraine was revealed. The homozygous carrier of the T rs5370 variant allele of the EDN1 gene significantly increases the risk of COPD comorbidity and cardiac pathology.

chronic obstructive pulmonary disease, endothelial dysfunction, Lys198Asn polymorphism.

1. Global Initiative for Chronic Obstructive Lung Disease. Global Strategy for the Diagnosis, Management and Prevention of Chronic Obstructive Pulmonary Disease. 2019. Available from: https://goldcopd.org/wp-content/uploads/2018/11/GOLD-2019-v1.7-FINAL-14Nov2018-WMS.pdf
2. Maselli DJ, Bhatt SP, Anzueto A, Bowler RP, DeMeo DL, Diaz AA, et al. Clinical epidemiology of COPD–Insights from 10 years of the COPDGene study. Chest. 2019;156(2):228-38.
3. Vestbo J, Hurd SS, Agustí AG, Jones PW, Vogelmeier C, Anzueto A, et al. Global Strategy for the Diagnosis, Management, and Prevention of Chronic Obstructive Pulmonary Disease. American Journal of Respiratory and Critical Care Medicine. 2018;187(4):347-65.
4. Marks GB. Guiding policy to reduce the burden of COPD: the role of epidemiological research. Thorax. 2018 May;73(5):405-6. DOI: 10.1136/ thoraxjnl-2017-211356
5. Divo M, Cote C, de Torres JP, Casanova C, Marin JM, Pinto-Plata V, et al. Comorbidities and risk of mortality in patients with chronic obstructive pulmonary disease. American journal of respiratory and critical care medicine. 2012 Jul 15;186(2):155-61. DOI: 10.1164/rccm.201201- 0034OC
6. Sameer Bansilal, José M. Castellano, Valentín Fuster. Global burden of CVD: focus on secondary prevention of cardiovascular disease. International journal of cardiology. December 2015;201:1-7.
7. Kaushal M, Shah PS, Shah AD, Francis SA, Patel NV, Kothari KK. Chronic obstructive pulmonary disease and cardiac comorbidities: A crosssectional study. Lung India: official organ of Indian Chest Society. 2016;33(4):404.
8. Stringer WW, Porszasz J, Bhatt SP, McCormack MC, Make BJ, Casaburi R. Physiologic Insights from the COPD Genetic Epidemiology Study. Chronic obstructive pulmonary diseases (Miami, Fla.). 2019;6(3):256-66.
9. Hawkins GA, Ampleford EJ, Ortega VE, Li X, Peters SP, Barr RG, et al. C54 COPD EPIDEMIOLOGY: TOBACCO: Evaluation Of Genetic Variants In Il6 And Il6r In The Nhlbi Subpopulations And Intermediate Outcome Measures In COPD Study (spiromics). American Journal of Respiratory and Critical Care Medicine. 2015;191:1.
10. Bosse Yohan. Updates on the COPD gene list. International journal of chronic obstructive pulmonary disease. 2012;7:607.
11. Hobbs BD, De Jong K, Lamontagne M, Bossé Y, Shrine N, Artigas MS, et al. Genetic loci associated with chronic obstructive pulmonary disease overlap with loci for lung function and pulmonary fibrosis. Nature genetics. 2017;49(3):426.
12. Wain LV, Shrine N, Artigas MS, Erzurumluoglu AM, Noyvert B, Bossini-Castillo L, et al. Genome-wide association analyses for lung function and chronic obstructive pulmonary disease identify new loci and potential druggable targets. Nature genetics. 2017;49(3):416.
13. Cho MH, McDonald MLN, Zhou X, Mattheisen M, Castaldi PJ, Hersh CP, et al. Risk loci for chronic obstructive pulmonary disease: a genomewide association study and meta-analysis. The lancet Respiratory medicine. 2014;2(3):214-25.
14. Lee Jin Hwa. Genetic susceptibility for chronic bronchitis in chronic obstructive pulmonary disease. Respiratory research. 2014;15(1):113.
15. Hardin M, Zielinski J, Wan ES, Hersh CP, Castaldi PJ, Schwinder E, et al. CHRNA3/5, IREB2, and ADCY2 are associated with severe chronic obstructive pulmonary disease in Poland. American journal of respiratory cell and molecular biology. 2012;47(2):203-8.
16. Zhou X, Baron RM, Hardin M, Cho MH, Zielinski J, Hawrylkiewicz I, et al. Identification of a chronic obstructive pulmonary disease genetic determinant that regulates HHIP. Human molecular genetics. 2011;21(6):1325-35.
17. Castaldi PJ, Cho MH, Cohn M, Langerman F, Moran S, Tarragona N, et al. The COPD genetic association compendium: a comprehensive online database of COPD genetic associations. Hum Mol Genet. 2010;19(3):526-34.
18. Kapustnik VA, Kostyuk IF, Melenevich AYa. Rol markerov endotelialnoj disfunkcii v progressirovanii hronicheskogo obstruktivnogo zabolevaniya legkih professionalnogo geneza. Eksperimentalna i klinichna medicina. 2015;4:36-42. [in Russian].
19. Sirotkin SA, Pribylov SA. Sistemnaya disfunkciya endoteliya u bolnyh hronicheskoj obstruktivnoj boleznyu legkih. Medline. ru. Rossijskij biomedicinskij zhurnal. 2007;8:41-8. [in Russian].
20. Kuzubova NA, Gichkin AYu, Surkova EA, Titova ON. Rol sistemnogo vospaleniya i endotelialnoj disfunkcii v razvitii levozheludochkovoj nedostatochnosti u bolnyh hronicheskoj obstruktivnoj boleznyu legkih. Pulmonologiya. 2014;4:41-5. [in Russian].
21. Androulakis Emmanuel, Christodoulos Stefanadis, Dimitris Tousoulis. Genetic Polymorphisms and the Vascular Endothelium. Introduction to Translational Cardiovascular Research. Springer; Cham: 2015. р. 129-42.
22. Voronina LP, Yatsenko MK, Trubnikov GA, Afanas’ ev YuA, Uklistaya TA, Polunina OS. Rol endotelina-1 v razvitii hronicheskoj obstruktivnoj patologii legkih. Fundamentalnye issledovaniya. 2004;6:45. [in Russian].
23. Smiianova YO, Pristupa LN, Harbuzova VY, Harbuzova YA. The association of LYS198ASN-polymorphism of endothelin-1 gene (EDN1) with development of arterial hypertension in Ukrainian population. Wiadomosci lekarskie (Warsaw, Poland: 1960). 2019;72(4):568-74.
24. Oleshko TB, Sviridenko DYu, Garbuzova VYu. Analiz zv’yazku Lys198Asn polimorfnih variantiv gena endotelinu-1 (EDN− 1) z ishemichnim aterotrombotichnim insultom v osib riznoyi stati. Klinichna ta eksperimentalna patologiya. 2016;15(1):99-103. [in Ukrainian].
25. Kaparianos A, Sampsonas F, Lykouras D, Efremidis G, Drakatos P, Karkoulias K, et al. Association of ET-1 gene polymorphisms with COPD phenotypes in a Caucasian population. Monaldi Arch Chest Dis. 2011;75(2):126-31.
26. Aggarwal PK, Jain V, Srinivasan R, Jha V. Maternal EDN1 G5665T polymorphism influences circulating endothelin-1 levels and plays a role in determination of preeclampsia phenotype. Journal of hypertension. 2009;27(10):2044-50.
27. 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. Journal of hypertension. 2001;19(10):1775-82.
28. Tanaka C, Kamide S, Takiuchi, Kawano Y, Miyata T. Evaluation of the Lys198Asn and 134 delA genetic polymorphisms of the endothelin-1 gene. Hypertens Res. 2004;27:367-71.

«Bulletin of problems biology and medicine» Issue 3 (152), 2019 year, 232-236 pages, index UDK 616.24-055.1:577.21

10.29254/2077-4214-2019-3-152-232-236