The role of polymorphic loci of the cytokine gene IL6 (C174G) in inflammatory and ulcerative lesions of the stomach

Purpose of the study. To study the distribution and role of polymorphic loci of the cytokine gene IL6 (C174G) in inflammatory and ulcerative lesions of the stomach. Material and research methods. In this study, the detection of the polymorphic IL6 gene (C174G) was carried out in patients with inflammatory and ulcerative lesions of the stomach (n=96) and healthy individuals (n=88). Results. Analysis of the features of the distribution of IL6 (C174G) gene polymorphism among the studied groups of patients with inflammatory and ulcerative diseases compared with healthy ones, its contribution to the pathogenetic mechanisms of their formation was found, which is confirmed by the presence of a pronounced tendency to increase the frequencies of the major C allele by 3.3 times (χ² = 3.3; P=0.1) and C/C genotype by 2.9 times (χ²=2.9; P=0.1) in chronic non-atrophic gastritis (CNG), as well as the minor allele G by 2.5 times (χ²=2.5; P=0.2) in ulcerative diseases of the stomach (GU). In addition, the contribution of the studied genetic marker is also confirmed by the presence of a tendency to increase the major allele C by 3.1 times (χ²=1.9; P=0.2) and the C/C genotype by 2.8 times (χ²=1.4; P=0.3; OR=2.8; 95%CI: 0.52-15.37) among patients with CNG compared with those in the group with chronic erosive gastritis (CEG), as well as a statistically significant increase in these indicators by 5.8 times (χ²=6.6; P=0.025) and 6.2 times (χ²= 6.3; P=0.025), respectively, in comparison with the group of patients with GU. No significant association between the likelihood of erosive chronic gastritis and C174G polymorphic loci of the IL6 gene was found compared to healthy individuals. However, compared with GU, the contribution of the major C allele and the major C/C genotype is confirmed by the presence of a trend towards their increase among patients with CEG by 1.9 (χ²=2.0; P=0.2) and 2.2 times (χ²=2.1; P=0.2). Conclusions: based on the results of the study, it can be argued that the C174G polymorphic loci of the IL6 gene play a significant role in the mechanisms of formation of inflammatory and ulcerative diseases of the stomach in Uzbekistan.

IL6 gene polymorphism (C174G), chronic non-atrophic gastritis, chronic erosive gastritis, gastric ulcer, risk of formation

1. Karbalaei M., Khorshidi M., Sisakht-pour B. et al. What are the effects of IL-1β (rs1143634), IL-17A promoter (rs2275913) and TLR4 (rs4986790) gene polymorphism on the outcomes of infection with H. pylori within as Iranian population; A systematic review and meta-analysis. Gene Reports. 2020; 20: 100735 doi: 10.1016/j.genrep.2020.100735.

2. Nejati S., Karkhah A., Darvish H. et al. Influence of Helicobacter pylori virulence factors CagA and VacA on pathogenesis of gastrointestinal disorders. Microb Pathog. 2018 Apr;117:43-48. doi: 10.1016/j.micpath.2018.02.016.

3. Akbieva D. S. The role of cytokines in the development of the disease gastroduodenal. Modern problems of science and education. 2017, No. 2, pp. 102-102. (in Russ.)@@ Акбиева Д. С. Роль цитокинов в развитии заболеваний гастродуоденальной зоны. Современные проблемы науки и образования. 2017. № 2. С. 102-102.

4. Miftahussurur M., Yamaoka Y. Helicobacter pylori virulence genes and host genetic polymorphisms as risk factors for peptic ulcer disease. Expert Rev Gastroenterol Hepatol. 2015;9(12):1535-1547. doi: 10.1586/17474124.2015.1095089.

5. Wang J., He W., Liu J. et al. Association of IL-6 polymorphisms with gastric cancer risk: evidences from a meta-analysis. Cytokine. 2012 Jul;59(1):176-83. doi: 10.1016/j.cyto.2012.03.032.

6. Pohjanen V.M., Koivurova O. P., Mäkinen J. M. et al.Interleukin 6 gene polymorphism -174 is associated with the diffuse type gastric carcinoma. Genes Chromosomes Cancer. 2013 Oct;52(10):976-82. doi: 10.1002/gcc.22093.

7. Moskalev A.V., Rudoy A. S., Apchel V. Ya. Heterogeneity of cytokines in immunopathogenesis of ulcers of duodenal gut, in erosion and chronic gastritis, associated with hereditary abnormalities of connecting tissue. Vestnik Rossiyskoy Voyenno-meditsinskoy akademii (Bulletin of the Russian Military Medical Academy). 2015;49(1):101-110. (in Russ.)@@ Москалёв А. В., Рудой А. С., Апчел В. Я. Гетерогенность цитокинов в иммунопатогенезе язвы двенадцатиперстной кишки, эрозивных и хронических гастритов, ассоциированных с наследственными нарушениями соединительной ткани. Вестник Российской Военно-медицинской академии. 2015. - Т. 49, - № 1. С. 101-110.

8. Shaimardanova E. Kh. [The study of genetic markers of the risk of developing gastric and duodenal ulcers]. Diss med sciens., Ufa, 2016, 28 P. (in Russ.)@@ Шаймарданова Э. Х. Изучение генетических маркеров риска развития язвенной болезни желудка и двенадцатиперстной кишки. Автореф. на соиск. уч. степени к. м. н., Уфа, 2016, С. 28.

9. Chae H.S., Kim Y. M., Chin Y. W. Atractylodin Inhibits Interleukin-6 by Blocking NPM-ALK Activation and MAPKs in HMC-1. Molecules. 2016 Sep 2;21(9):1169. doi: 10.3390/molecules21091169.

10. Rasool K.H., Mahmood Alubadi A. E., Al-Bayati I.F.I. The role of Serum Interleukin-4 and Interleukin-6 in Helicobacter pylori-infected patients. Microb Pathog. 2022 Jan;162:105362. doi: 10.1016/j.micpath.2021.105362.

11. Sampaio A.M., Balseiro S. C., Silva M. R. et al. Association Between IL-4 and IL-6 Expression Variants and Gastric Cancer Among Portuguese Population. GE Port J Gastroenterol. 2015 Jul 4;22(4):143-152. doi: 10.1016/j.jpge.2015.04.001.