Role of IL-1β, TNF-α, IL-10, IL-17, and IL-4 gene polymorphisms in the pathogenesis of chronic rhinosinusitis with nasal polyps

N. Baranova, B. Molotilov, L. Ashchina, N. Shkurova
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Abstract

Background: chronic rhinosinusitis with nasal polyps (CRSwNP) is a multifactorial disease, those mechanisms are not fully understood. A significant role of cytokines, e.g., interleukin (IL)-1β, tumor necrosis factor (TNF) α, IL-10, IL-17А, IL-4, and their genes, in the pathogenesis and predisposition to CRSwNP and treatment efficacy is established. Aim: to investigate IL-1β (Т-31С), TNF-α (G-308A), IL-10 (G-1082A), IL-17(G-197A), and IL-4 (С-589Т) gene polymorphisms and their role in CRSwNP pathogenesis. Patients and Methods: this open-label, prospective, randomized study enrolled 100 patients with CRSwNP. The control group included 72 healthy volunteers. DNA was isolated from the whole venous blood. IL-1β (Т-31С), TNF-α (G-308A), IL-10 (G-1082A), IL-17 (G-197A), and IL-4 (С-589Т) gene polymorphisms were assessed by the real-time polymerase chain reaction (PCR). Results: the analysis of IL-4 (С-589Т) gene polymorphism has demonstrated that 589С/С genotype is more common in CRSwNP patients compared to the controls (р=0.021, odds ratio/OR=1.248 [0.449–3.465]). The analysis of IL-10 (G-1082A) gene polymorphism has demonstrated that 1082А/A genotype is more common in CRSwNP patients compared to the controls (p=0.043, OR=1.027 [0.374–2.830]). The analysis of IL-17 (G-197A) gene polymorphism has demonstrated that 197A/А genotype is more common in CRSwNP patients than in the controls (p=0.046, OR=7.250 [0.863–2.532]). The analysis of TNF-α (G-308A) gene polymorphism has demonstrated that 308 G/G genotype is more common in CRSwNP patients compared to the controls (p=0.045, OR=1.789 [0.892–4.776]). Conclusion: the most relevant predictors of the increased risk of CRSwNP are 589С/С genotype of IL-4 gene, 1082А/A genotype of IL-10 gene, 197A/А genotype of IL-17 gene, and 308 G/G genotype of TNF-α gene. The analysis of essential cytokine gene polymorphisms, i.e., IL- 1β (Т-31С), TNF-α (G-308A), IL-10 (G-1082A), IL-17 (G-197A), and IL-4 (С-589Т), allows assessing genetic predisposition to CRSwNP. This technique is an important tool for predicting treatment efficacy. KEYWORDS: chronic rhinosinusitis with nasal polyps, cytokines, genotype, gene polymorphism, pathogenic mechanisms. FOR CITATION: Baranova N.I., Molotilov B.A., Ashchina L.A., Shkurova N.A. Role of IL-1β, TNF-α, IL-10, IL-17, and IL-4 gene polymorphisms in the pathogenesis of chronic rhinosinusitis with nasal polyps. Russian Medical Inquiry. 2022;6(2):57–61 (in Russ.). DOI: 10.32364/2587-6821-2022-6-2-57-61.
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背景:慢性鼻窦炎伴鼻息肉(CRSwNP)是一种多因素疾病,其发病机制尚不完全清楚。证实了白细胞介素(IL)-1β、肿瘤坏死因子(TNF) α、IL-10、IL-17А、IL-4等细胞因子及其基因在CRSwNP发病、易感性及治疗效果中的重要作用。目的:探讨IL-1β (Т-31С)、TNF-α (G-308A)、IL-10 (G-1082A)、IL-17(G-197A)、IL-4 (С-589Т)基因多态性及其在CRSwNP发病机制中的作用。患者和方法:这项开放标签、前瞻性、随机研究纳入了100例CRSwNP患者。对照组包括72名健康志愿者。从整个静脉血中分离出DNA。实时聚合酶链反应(PCR)检测IL-1β (Т-31С)、TNF-α (G-308A)、IL-10 (G-1082A)、IL-17 (G-197A)和IL-4 (С-589Т)基因多态性。结果:IL-4 (С-589Т)基因多态性分析显示,与对照组相比,589С/С基因型在CRSwNP患者中更为常见(r =0.021,比值比/OR=1.248[0.449-3.465])。IL-10 (G-1082A)基因多态性分析表明,与对照组相比,1082А/A基因型在CRSwNP患者中更为常见(p=0.043, OR=1.027[0.374-2.830])。IL-17 (G-197A)基因多态性分析表明,197A/А基因型在CRSwNP患者中比对照组更常见(p=0.046, OR=7.250[0.863-2.532])。TNF-α (G- 308a)基因多态性分析表明,308 G/G基因型在CRSwNP患者中比对照组更常见(p=0.045, OR=1.789[0.892-4.776])。结论:IL-4基因589С/С基因型、IL-10基因1082А/A基因型、IL-17基因197A/А基因型、TNF-α基因308 G/G基因型是CRSwNP风险增加的最相关预测因子。必需细胞因子基因多态性的分析,即IL- 1β (Т-31С), TNF-α (G-308A), IL-10 (G-1082A), IL-17 (G-197A)和IL-4 (С-589Т),可以评估CRSwNP的遗传易感性。该技术是预测治疗效果的重要工具。关键词:慢性鼻窦炎伴鼻息肉,细胞因子,基因型,基因多态性,致病机制。引用本文:Baranova N.I., Molotilov B.A, Ashchina L.A, Shkurova N.A. IL-1β、TNF-α、IL-10、IL-17和IL-4基因多态性在慢性鼻窦炎伴鼻息肉发病中的作用。俄罗斯医学调查。2022;6(2):57-61(俄文)。DOI: 10.32364 / 2587-6821-2022-6-2-57-61。
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