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伊朗慢性丙型肝炎患者人类 TRIM22 基因表达与聚乙二醇干扰素 α-2a 和利巴韦林联合治疗应答的相关性。

Associations between human TRIM22 gene expression and the response to combination therapy with Peg-IFNα-2a and ribavirin in Iranian patients with chronic hepatitis C.

机构信息

Department of Virology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran.

出版信息

J Med Virol. 2014 Sep;86(9):1499-506. doi: 10.1002/jmv.23985. Epub 2014 May 29.

Abstract

Interferons are able to exert an antiviral effect against hepatitis C virus (HCV) infection via induction of interferon-stimulated genes (ISGs). This study tested whether differential expression of an important ISG with antiviral properties, tripartite motif 22 (TRIM22), correlates with a response to Peg-IFNα-2a/RBV combination therapy in treatment-naive patients with chronic hepatitis C. A total of 32 patients with chronic hepatitis C were enrolled in this study and received standard Peg-IFNα-2a/RBV combination therapy. HCV viral load was measured during treatment, at the end of treatment, and 6 months later to determine the treatment outcome. Quantitative real-time PCR was used to assess the expression levels of TRIM22 in peripheral blood mononuclear cells (PBMCs) of the patients before antiviral therapy. Of the 32 patients, 26 (81.3%) were males. In this study, there were 16 (50%) individuals with a sustained virologic response (SVR), and a virologic relapse was observed in the remaining half of the subjects. Testing for the presence of genomic HCV RNA in blood during therapy revealed a rapid virologic response (RVR) in 10 (31.2%) and a partial and complete early virologic response (EVR) in 8 (25%) and 24 (75%) of the cases, respectively. TRIM22 mRNA levels were significantly higher in patients with a sustained virologic response than in relapsers (P = 0.002) and in patients with a rapid virologic response than in the others (P = 0.040). No statistically significant difference was seen in the expression of TRIM22 between patients with a partial early virologic response and a complete early virologic response. This study showed that pretreatment upregulation of TRIM22 may be associated with responsiveness to Peg-IFNα-2a/RBV combination therapy.

摘要

干扰素通过诱导干扰素刺激基因(ISGs)对丙型肝炎病毒(HCV)感染发挥抗病毒作用。本研究检测了具有抗病毒特性的重要 ISG 三结构域蛋白 22(TRIM22)的差异表达是否与聚乙二醇干扰素α-2a/利巴韦林联合治疗初治慢性丙型肝炎患者的反应相关。本研究共纳入 32 例慢性丙型肝炎患者,接受标准聚乙二醇干扰素α-2a/利巴韦林联合治疗。在治疗期间、治疗结束时和 6 个月后测量 HCV 病毒载量,以确定治疗结果。采用实时定量 PCR 检测患者抗病毒治疗前外周血单个核细胞(PBMCs)中 TRIM22 的表达水平。32 例患者中,26 例(81.3%)为男性。本研究中,16 例(50%)患者获得持续病毒学应答(SVR),其余一半患者出现病毒学复发。在治疗期间检测血液中是否存在基因组 HCV RNA 显示,10 例(31.2%)患者出现快速病毒学应答(RVR),8 例(25%)和 24 例(75%)患者分别出现部分和完全早期病毒学应答(EVR)。持续病毒学应答患者的 TRIM22 mRNA 水平明显高于复发患者(P=0.002)和快速病毒学应答患者(P=0.040)。部分早期病毒学应答患者和完全早期病毒学应答患者的 TRIM22 表达无统计学差异。本研究表明,预处理时 TRIM22 的上调可能与对聚乙二醇干扰素α-2a/利巴韦林联合治疗的反应性相关。

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