Tian Cui-Huan, Dai Jun, Zhang Wei, Liu Yan, Yang Yan
Health Management Center, QiLu Hospital of Shandong University, Jinan, Shandong Province.
School of Medicine, Shandong University.
Medicine (Baltimore). 2019 Jun;98(23):e15924. doi: 10.1097/MD.0000000000015924.
To explore interleukin-17 (IL-17) and its epigenetic regulation during the progression of chronic hepatitis B virus (HBV) infection.A total of 162 patients with chronic HBV infection, including 75 with chronic hepatitis B (CHB), 54 with hepatitis B-associated liver cirrhosis and 33 with hepatitis B-associated hepatocellular carcinoma (HBV-HCC), were enrolled in this study. Thirty healthy adults of the same ethnicity were enrolled in the control group. Whole venous blood was obtained from the patients and normal controls (n = 30). Clinical and laboratory parameters were assessed, and we performed enzyme-linked immunosorbent assay and quantitative real-time PCR to measure the serum levels and relative mRNA expression of IL-17, respectively. IL-17 promoter methylation in peripheral blood mononuclear cells was assessed by methylation-specific PCR. We analyzed the serum and mRNA levels of IL-17 and IL-17 promoter methylation in the 4 groups as well as the effect of methylation on serum IL-17 levels. Correlations between the IL-17 promoter methylation status and clinical parameters were analyzed by Spearman correlation analysis.Compared to the normal control group, the patient groups exhibited significantly higher serum and relative mRNA levels of IL-17. The methylation distribution among the patients was significantly lower than that among the normal controls (P < .05), with the HBV-HCC group showing the lowest IL-17 gene methylation frequency. The average IL-17 promoter CG methylation level was negatively correlated with IL-17 mRNA expression (r = -0.39, P = .03), and negative correlations between IL-17 promoter methylation and prothrombin time activity (r = -0.585, P = .035), alanine aminotransferase (r = -0.522, P < .01), aspartate aminotransferase (r = -0.315, P < .05), and the model for end-stage liver disease score (r = -0.461, P < .05) were observed. IL-17 serum levels in the methylated-promoter groups were significantly lower than those in the unmethylated-promoter groups.IL-17 expression and promoter methylation were associated with chronic HBV infection progression, especially in the HBV-HCC group. The IL-17 promoter status may help clinicians initiate the correct treatment strategy at the CHB stage.
探讨慢性乙型肝炎病毒（HBV）感染进展过程中白细胞介素-17（IL-17）及其表观遗传调控。本研究共纳入162例慢性HBV感染患者，其中包括75例慢性乙型肝炎（CHB）患者、54例乙型肝炎相关性肝硬化患者和33例乙型肝炎相关性肝细胞癌（HBV-HCC）患者。选取30名同种族健康成年人作为对照组。采集患者和正常对照者（n = 30）的全静脉血。评估临床和实验室参数，并分别采用酶联免疫吸附测定法和定量实时PCR检测血清中IL-17水平及相对mRNA表达。通过甲基化特异性PCR评估外周血单个核细胞中IL-17启动子甲基化情况。分析4组中IL-17的血清和mRNA水平、IL-17启动子甲基化情况以及甲基化对血清IL-17水平的影响。采用Spearman相关性分析IL-17启动子甲基化状态与临床参数之间的相关性。与正常对照组相比，患者组血清和IL-17相对mRNA水平显著升高。患者组的甲基化分布显著低于正常对照组（P < 0.05），其中HBV-HCC组的IL-17基因甲基化频率最低。IL-17启动子CG平均甲基化水平与IL-17 mRNA表达呈负相关（r = -0.39，P = 0.03），且观察到IL-17启动子甲基化与凝血酶原时间活性（r = -0.585，P = 0.035）、丙氨酸氨基转移酶（r = -0.522，P < 0.01）、天冬氨酸氨基转移酶（r = -0.315，P < 0.05）以及终末期肝病模型评分（r = -0.461，P < 0.05）之间呈负相关。启动子甲基化组的IL-17血清水平显著低于未甲基化启动子组。IL-17表达和启动子甲基化与慢性HBV感染进展相关，尤其是在HBV-HCC组。IL-17启动子状态可能有助于临床医生在CHB阶段制定正确的治疗策略。
