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STAT4基因多态性与慢性乙型肝炎患者细胞因子分泌水平的相关性研究
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Abstract:
目的:通过检测慢性乙型肝炎(chronic hepatitis B virus, CHB)患者信号转导与转录激活因子4 (signal transducer and activator of transcription 4, STAT4)基因的rs7574865位点突变情况,探究CHB患者STAT4表达与细胞因子分泌水平的相关性。方法:收集昆明市第三人民医院2020年8月至2022年8月确诊的300例CHB患者和300例健康体检者为研究对象。采用实时荧光定量PCR技术检测两组STAT4 rs7574865位点的基因多态性。采用酶联免疫吸附法检测CHB患者外周血清IL-21、IL-35、IL-37和TGF-β水平。结果:CHB患者组STAT4基因rs7574865位点的GT、GG基因型高于对照组(P < 0.01),G等位基因频率显著高于对照组(P < 0.01)。GT型CHB患者IL-21及IL-35水平明显高于TT及GG型(P < 0.05)。结论:STAT4基因多态性与CHB的发生存在一定相关性,GT型患者IL-21、IL-35水平明显升高,临床可通过检测CHB患者STAT4基因多态性及IL-21、IL-35水平评估CHB发生的风险性。
Objective: To detect the rs7574865 mutation of signal transducer and activator of transcription 4 (STAT4) gene in patients with chronic hepatitis B (CHB), and explore the correlation between STAT4 expression and cytokine secretion level in CHB patients. Method: A total of 300 CHB patients and 300 healthy individuals diagnosed from August 2020 to August 2022 at Kunming Third Peo-ple’s Hospital were collected as research subjects. Real time fluorescence quantitative PCR technol-ogy was used to detect gene polymorphism at the STAT4 rs7574865 locus in two groups. The IL-21, IL-35, IL-37 and TGF-β in peripheral blood of CHB patients were detected by enzyme-linked im-munosorbent assay. Results: The GT and GG genotypes at rs7574865 of STAT4 gene in patients with CHB were higher than those in the control group (P < 0.01), and the frequency of G allele frequency was significantly higher than that in the control group (P < 0.01). The levels of IL-21 and IL-35 in GT type CHB patients were significantly higher than those in TT and GG types (P < 0.05). Conclusion: There is a certain correlation between STAT4 gene polymorphism and the occurrence of CHB. The levels of IL-21 and IL-35 are significantly increased in GT type patients. Clinical evaluation of the risk of CHB can be achieved by detecting STAT4 gene polymorphism and IL-21 and IL-35 levels in CHB patients.
[1] | 李娜. 外泌体在乙肝病毒传播及其相关免疫反应中的研究进展[J]. 临床与病理杂志, 2022, 42(11): 2837-2842. |
[2] | 吴瑛, 王涛. 慢性乙型病毒性肝炎流行病学特征及影响因素分析[J]. 现代实用医学, 2022, 34(5): 686-687. |
[3] | Furuta, M., Tanaka, H., Shiraishi, Y., et al. (2018) Characterization of HBV Integration Patterns and Timing in Liver Cancer and HBV-Infected Livers. Oncotarget, 9, 25075-25088. https://doi.org/10.18632/oncotarget.25308 |
[4] | 杨红梅, 邱铖, 黄宇超, 孙文峰. 恩替卡韦联合甘草酸二铵肠溶胶囊治疗慢性乙型病毒性肝炎的临床研究[J]. 中国临床药理学杂志, 2023, 39(17): 2440-2444. |
[5] | 潘莉, 付贤翠. 2008-2017年昆明市西山区甲乙类传染病流行病学特征分析[J]. 应用预防医学, 2019, 25(1): 18-22. |
[6] | 余婷婷, 王红英, 张润武, 白经, 普冬, 李冬玲. 昆明地区1452例低病毒载量慢乙肝患者耐药突变相关位点的分析[J]. 昆明医科大学学报, 2022, 43(9): 43-47. |
[7] | Zhou, H., Jia, X., Hu, K., et al. (2021) TMEM2 Binds to CSNK2A3 to Inhibit HBV Infection via Activation of the JAK/STAT Pathway. Experimental Cell Research, 400, Article ID: 112517.
https://doi.org/10.1016/j.yexcr.2021.112517 |
[8] | 中华医学会肝病学分会, 中华医学会感染病学分会. 慢性乙型肝炎诊断标准(2015年版) [J]. 中西医结合肝病杂志, 2015, 25(6): 384-386. |
[9] | 朴金梅, 刘梦, 李成成, 等. STAT4 rs7574865GG基因型与GT+TT基因型肝癌患者相关危险因素对比分析[J]. 中华肿瘤防治杂志, 2017, 24(2) : 84-86. |
[10] | Korman, B.D., Kastner, D.L., Gregersen, P.K., et al. (2008) STAT4: Genetics, Mechanisms and Implications for Autoimmunity. Current Allergy and Asthma Reports, 8, 398-403. https://doi.org/10.1007/s11882-008-0077-8 |
[11] | Lamana, A., Pezsantalla, M., Castillogonzaez, R., et al. (2015) The Minor Allele of rs7574865 in the STAT4 Gene Is Associated with Increased mRNA and Protein Expression. PLOS ONE, 10, e0142683.
https://doi.org/10.1371/journal.pone.0142683 |
[12] | 郄燕, 常培叶, 杜立平, 赵乌云. Th17/Treg比例联合FIB-4和APRI评分对HBV相关肝纤维化的评估价值分析[J]. 热带医学杂志, 2023, 23(1): 50-53. |
[13] | 付海洋, 时维平, 付广明, 张蓓, 史海磊, 李雪健. Th17/Treg值在慢性乙型肝炎肝纤维化进展中的意义[J]. 中外医疗, 2020, 39(8): 180-183. |
[14] | Liu, B., Gao, W., Zhang, L., et al. (2017) Th17/Treg Imbalance and Increased Interleukin-21 Are Asso-ciated with Liver Injury in Patients with Chronic Severe Hepatitis B. International Immunopharmacology, 46, 48-55.
https://doi.org/10.1016/j.intimp.2017.02.019 |
[15] | 邓昭敏, 刘琳, 熊颖妮, 等. IL-35在慢性乙型肝炎发病过程中的免疫抑制作用[J]. 国际检验医学杂志, 2018, 39(19): 2376-2378, 2382. |
[16] | 王新伟, 杨道坤, 梁海军, 等. 白细胞介素-35对慢性乙型肝炎患者外周血Th17细胞的影响及其临床意义[J]. 免疫学杂志, 2017, 33(10): 885-890. |
[17] | Yang, L.L., Jia, S.N., Shao, X., et al. (2019) Interleukin-35 Modulates the Balance between Viral Spe-cific CD4+CD25+CD127dim/? Regulatory T Cells and T Helper 17 Cells in Chronic Hepatitis B Virus Infection. Virology Journal, 16, Article No. 48. https://doi.org/10.1186/s12985-019-1158-0 |
[18] | Shi, Y.Y., Dai, M.J., Wu, G.P., et al. (2015) Levels of Interleukin-35 and Its Relationship with Regulatory T-Cells in Chronic Hepatitis B Patients. Viral Im-munology, 28, 93-100. https://doi.org/10.1089/vim.2014.0058 |
[19] | Gravano, D.M. and Vignali, D.A. (2012) The Battle against Immunopathology: Infectious Tolerance Mediated by Regulatory T Cells. Cellular & Molecular Life Sci-ences, 69, 1997-2008. https://doi.org/10.1007/s00018-011-0907-z |
[20] | Qiao, Y., Han, X., Guan, G., et al. (2016) TGF-β Triggers HBV cccDNA Degradation through AID-Dependent Deamination. FEBS Letters, 590, 419-427. https://doi.org/10.1002/1873-3468.12058 |