Interferon-stimulated gene 15 in hepatitis B-related liver diseases.
Interferon-stimulated gene 15 in hepatitis B-related liver diseases.
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DOI：
10.18632/oncotarget.11955
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发表时间：
2016-10-18
期刊：
影响因子：
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通讯作者：
Velavan TP
中科院分区：
文献类型：
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作者：
Hoan NX;Van Tong H;Giang DP;Toan NL;Meyer CG;Bock CT;Kremsner PG;Song LH;Velavan TP
本研究旨在探讨干扰素刺激基因15（ISG 15）多态性、血清ISG 15水平及表达与HBV相关性肝病的关系。在766例HBV感染者和223例对照者中筛选ISG 15启动子和基因的两个外显子的多态性。通过ELISA测量可溶性ISG 15水平。通过qRT-PCR定量36个肿瘤和邻近非肿瘤组织中的ISG 15 mRNA表达。发现外显子2等位基因rs 1921 A与HBV相关肝病进展减缓相关（LC与CHB：OR = 0.6，95%CI = 0.4-0.8，校正P = 0.003; HCC与CHB：OR = 0.6，95%CI = 0.4-0.9，校正P = 0.005）。rs 1921 AA基因型与AST、ALT和总胆红素水平降低相关，而与凝血酶原水平升高相关（P < 0.05）。HBV患者血清ISG 15水平高于对照组（P < 0.0001），且与HBV相关性肝病呈正相关，LC患者血清ISG 15水平最高。ISG 15水平与HBV-DNA载量呈正相关（P = 0.001）。在HCC患者的非肿瘤组织中，与非HBV感染相比，HBV感染的ISG 15 mRNA表达增加（P = 0.016）。ISG 15 rs 1921变异和ISG 15表达与HBV相关性肝病相关综上所述，ISG 15似乎是参与HBV复制和触发HBV相关肝病进展的前病毒因子。
This study investigates the association of Interferon-stimulated gene 15 (ISG15) polymorphisms, ISG15 serum levels and expression with HBV-related liver diseases. The ISG15 promoter and the two exons of the gene were screened for polymorphisms in 766 HBV-infected patients and in 223 controls. Soluble ISG15 levels were measured by ELISA. ISG15 mRNA expression was quantified by qRT-PCR in 36 tumor and adjacent non-tumor tissues. The exon 2 allele rs1921A was found associated with decreased progression of HBV-related liver diseases (LC vs. CHB: OR = 0.6, 95%CI = 0.4-0.8, adjusted P = 0.003; HCC vs. CHB: OR = 0.6, 95%CI = 0.4-0.9, adjusted P = 0.005). The rs1921AA genotype was associated with low levels of AST, ALT and total bilirubin, but with high prothrombin levels (P < 0.05). ISG15 serum levels were higher among HBV patients compared to controls (P < 0.0001) and positively associated with HBV-related liver diseases, with highest levels among LC patients. ISG15 levels were correlated with HBV-DNA loads (P = 0.001). In non-tumor tissues from HCC patients, ISG15 mRNA expression was increased in HBV compared to non-HBV infection (P = 0.016). The ISG15 rs1921 variant and ISG15 expression are associated with HBV-related liver diseases. Taken together, ISG15 appears to be a proviral factor involved in HBV replication and triggering progression of HBV-related liver diseases.