Polymorphism of cytokine genes in patients with liver cirrhosis


Cite item

Full Text

Open Access Open Access
Restricted Access Access granted
Restricted Access Subscription or Fee Access

Abstract

Today there is a need to create a set of laboratory tests, including genetic ones, to determine the risk of developing and progression of liver cirrhosis (LC). The aim of the work: to determine the concentration of tumor necrosis factor-a (TNF-a), interleukin 6 (IL-6) and vascular endothelial growth factor (VEGF) in blood serum, as well as their polymorphism genes - TNF-a in the -308G /A region (rs1800629), IL-6 in the -174G/C region (rs1800795) and VEGFA in the -634G/C region (rs2010963) - in LC patients in the Perm region. Material and methods. We examined 46 patients with LC of viral (HCV) and alcoholic etiology and 80 healthy donors. Determined the serum concentration of TNF-a, IL-6 and VEGF by ELISA. The analysis of genetic markers TNF-a -308G/A, IL-6 -174C/G and VEGFA -634G/C by qPCR method. Results. The development of LC is accompanied by activation of inflammatory mechanisms with an increase in the level of proinflammatory cytokines TNF-a (p=0,0001), IL-6 (p=0,0001) and endothelial damage with activation of neoangiogenesis due to hyperproduction of VEGf (p=0,01) in serum. The study of single nucleotide polymorphisms of cytokine genes showed a significantly higher frequency of occurrence in the group of LC patients than in donors of the minor allele A of the TNF-a -308G/A gene, the CG genotype of the IL-6 -174C/G gene and the CC genotype of the VEGFA-634G/C gene. It allows us to attribute them to possible genetic predictors of LC development. Conclusion. Determination of genetic markers TNF-a -308G/A, IL-6 -174C/G and VEGFA-634G/C allows us to assess the increased risk of possible development of LC under the influence of various etiological factors.

Full Text

Restricted Access

About the authors

I. A Bulatova

Academician E.A. Vagner Perm State Medical University of the Ministry of Healthcare of Russia

Email: bula.19770mail.ru
614990, Perm, 26 Petropavlovskaya Str

T. P Shevlyukova

Tyumen State Medical University of the Ministry of Healthcare of Russia

Email: tata21.010mail.ru
625023, Tyumen, 54 Odesskaya Str

A. P Shchekotova

Academician E.A. Vagner Perm State Medical University of the Ministry of Healthcare of Russia

Email: al_shchekotova0mail.ru
614990, Perm, 26 Petropavlovskaya Str

S. V Paducheva

City Clinical Hospital No. 2 named after Fedor Khristoforovich Gral

Email: paducheva_sv0mail.ru
614068, Perm, 230 Permskaya Str

A. I Martynov

A.I. Yevdokimov Moscow State University of Medicine and Dentistry of the Ministry of Healthcare of Russia

Email: anatmartynov0mail.ru
127473, Moscow, 20/1 Delegatskaya Str

References

  1. Moon A.M., Singal A.G., Tapper E.B. Contemporary epidemiology of chronic liver disease and cirrhosis. Clin Gastroenterol Hepatol. 2020; 18(12): 2650-66. https://dx.doi.org/10.1016/jxgh.2019.07.060.
  2. GBD 2017 Cirrhosis Collaborators. The global, regional, and national burden of cirrhosis by cause in 195 countries and territories, 1990-2017: A systematic analysis for the Global Burden of Disease Study 2017. Lancet Gastroenterol Hepatol. 2020; 5(3): 245-66. https://dx.doi.org/10.1016/S2468-1253(19)30349-8.
  3. Кузьмина Ю.С., Жмуров В.А., Мищенко Т.А. с соавт. Клинико-лабораторные факторы неблагоприятного прогноза заболевания у пациентов с циррозом печени. Медицинская наука и образование Урала. 2020; 3: 13-16. @@Kuzmina Yu.S., Zhmurov V.A., Mishchenko T.A. et al. Clinical and laboratory factors of unfavorable prognosis of the disease in patients with cirrhosis of the liver Meditsinskaya nauka i obrazovaniye Urala = Medical Science and Education of the Urals. 2020; 3: 13-16 (In Russ.). https://dx.doi.org/10.36361/1814-8999-2020-21-3-12-16.
  4. Brenner D.A. Molecular pathogenesis of liver fibrosis. Trans Am Clin Climatol Assoc. 2009; 120: 361-68.
  5. Долгих О.В., Падучева С.В., Булатова И.А., Щекотова А.П. Особенности иммунологического ответа при циррозе печени в зависимости от степени его тяжести. Российский иммунологический журнал. 2017; 3: 463-465. @@Paducheva S.V., Dolgikh O.V., Bulatova I.A., Shekotova A.P. Peculiarities of immunological responce during liver cirrhosis depending on severity level. Rossiyskiy immunologicheskiy zhurnal = Russian Journal of Immunology. 2017; 3: 463-465 (In Russ.)
  6. Булатова И.А. Васкулоэндотелиальный фактор роста и полиморфизм гена VEGF (rs2010963) в патогенезе хронического вирусного гепатита С. Современные проблемы науки и образования. 2013; 6: 635. @@Bulatova I.A. Vascular endothelial grow factor and polymorphism of VEGF (RS2010963) gene in pathogenesis of chronic hepatitis C. Sovremennye problemy nauki i obrazovaniia = Modern Issues of Science and Education. 2013; 6: 635 (In Russ.)
  7. Щекотов В.В., Булатова И.А., Щекотова А.П. с соавт. Неинвазивная оценка темпа прогрессирования фиброза печени. Современные проблемы науки и образования. 2016; 1: 5. @@Schekotov V.V., Bulatova I.A., Schekotova A.P. et al. Noninvasive evaluation of progress of liver fibrosis. Sovremennye problemy nauki i obrazovaniia = Modern Issues of Science and Education. 2016; 1: 5 (In Russ.)
  8. Huang H., Shiffman M.L., Friedman S. et al. A 7 gene signature identifies the risk of developing cirrhosis in patients with chronic hepatitis C. Hepatology. 2007; 46(2): 297-306. https://dx.doi.org/10.1002/hep.21695.
  9. Guinot F., Szafranski M., Ambroise C. et al. Learning the optimal scale for GWAS through hierarchical SNP aggregation. BMC Bioinformatics. 2018; 19(1): 459. https://dx.doi.org/10.1186/s12859-018-2475-9.
  10. Бодиенкова Г.М., Титова Ж.В. Роль полиморфизма и экспрессии отдельных генов цитокинов в формировании патологии (обзор). Успехи современного естествознания. 2015; 1-4: 616-620. @@Titova Z.V., Bodienkova G.M. Polymorphism and gene expression cytokines in the formation of pathology (review). Uspekhi sovremennogo yestestvoznaniya = Successes of Modern Natural Science. 2015; 1-4: 616-620 (In Russ.)
  11. EASL Clinical Practice Guidelines: Management of alcohol-related liver disease. European Association for the Study of the Liver. J Hepatol. 2018; 69(1): 154-81. https://dx.doi.org/10.1016/j.jhep.2018.03.018.
  12. Albillos A., Lario М., Alvarez-Mon М. Cirrosis-associated immune distinctive features and clinical relevance. J Hepatol 2014; 61(6): 1385-96. https://dx.doi.org/10.1016/j.jhep.2014.08.010.
  13. Dirchwolf М., Podhorzer А., Morino М. et al. Immune dysfunction in cirrhosis: Distinct cytokines phenotypes according to cirrhosis severity. J Cytokine. 2016; 77: 14-25. https://dx.doi.org/10.1016/j.cyto.2015.10.006.
  14. Martinez-Esparza M., Tristan-Manzano М., Ruiz-Alcaraz A.J., Garda-Penarrubia Р. Inflammatory status in human hepatic cirrhosis. World J Gastroenterol. 2015; 21(41): 11522-41. https://dx.doi.org/10.3748/wjg.v21.i41.11522.
  15. Скуратов А.Г, Лызиков А.Н., Воропаев Е.В., Осипкина О.В. Уровень интерлейкина-6 как показатель тяжести цирроза печени и портальной гипертензии. Проблемы здоровья и экологии. 2016; 4: 110-114. @@Skuratov A.G., Lyzikov A.N., Voropaev E.V., Osipkina O.V.Interleukin-6 as an indicator of severity of liver cirrhosis and portal hypertension. Problemy zdorov'ya i ekologii = Issues of Health and Ecology. 2016; 4: 110-114 (In Russ.)
  16. Николаева Л.И., Колотвин А.В., Самоходская Л.М. с соавт. Анализ влияния генетических факторов вируса гепатита С и полиморфизма генов инфицированных людей на развитие фиброза печени. Эпидемиология и инфекционные болезни. 2012; 5: 7-13. @@Nikolaeva L.I., Kolotvin A.V., Samokhodskaya L.M. et al. Analysis of the influence of genetic factors of hepatitis C virus and gene polymorphism in infected patients on the development of liver fibrosis. Epidemiologiya i infektsionnyye bolezni = Epidemiology and Infectious Diseases. 2012; 5: 7-13 (In Russ.)
  17. Скуратов А.Г, Лызиков А.Н., Воропаев Е.В., Осипкина О.В. Молекулярно-генетический анализ полиморфизма генов IL-4, TNF-a у пациентов с циррозом печени и портальной гипертензией. Проблемы здоровья и экологии. 2017; 2: 110-114. @@Skuratov A.G., Lyzikov A.N., Voropayev E.V., Osipkina O.V. The molecular-genetic analysis of polymorphism of IL-4, TNF-a genes in patients with liver cirrhosis and portal hypertension. Problemy zdorov'ya i ekologii = Issues of Health and Ecology. 2017; 2: 110-114 (In Russ.)
  18. Giannitrapani L., Soresi M., Balasus D. et al. Genetic association of interleukin-6 polymorphism (-174 G/C) with chronic liver diseases and hepatocellular carcinoma. World J Gastroenterol. 2013; 19(16): 2449-55. https://dx.doi.org/10.3748/wjg.v19.i16.2449.

Supplementary files

Supplementary Files
Action
1. JATS XML
Download

Copyright (c) 2022 Bionika Media