IP-10，CXCL10(10千道尔顿的干扰素γ诱导蛋白)的表达慢性乙型肝炎感染中的重要性最近已经被强调。在这个报告中，我们研究在CXCL10自然发生的序列变异对HBV感染后疾病进展和肝损伤的影响。在来自医院的病例对照研究中，一共包括了613名和1787名分别来自北京和重庆的汉族HBV携带者。我们系统地筛选了CXCL10基因序列变异，研究了其与来自北京和重庆的中国人群中慢性乙型肝炎病毒感染疾病进展易感性之间的关系。功能分析的进行验证了相关的遗传变异的生物学意义。我们发现在CXCL10启动子上的G-201A多态性位点与男性HBV携带者疾病进展的易感性有关。功能分析显示G-201A的多态性改变了核蛋白的结合亲和力并调控了CXCL10的表达。我们观察到在疾病容易进展的基因型中，干扰素γ刺激的外周血单个核细胞中CXCL10转录水平较高。酶联免疫吸附试验和免疫组化分析显示在疾病进展的乙型肝炎病毒携带者中，血清及肝组织中CXCL10产物增多。在CXCL10基因启动子上典型的多态性G-201A位点可能是遗传变异的一部分，这种遗传变异与慢性乙肝病毒感染后疾病进展的个体易感性相关。
吉林大学第一医院肝胆胰内科 吕娟 牛俊奇 摘译
本文首次发表于[Gastroenterology, 2008,134(3):716-726]
Regulatory Polymorphisms in the Promoter of CXCL10 Gene and Disease Progression in Male Hepatitis B Virus Carriers
Background & Aims：The importance of expression of interferon gamma inducible protein of 10 kilodaltons (IP-10, CXCL10) during chronic hepatitis B virus (HBV) infection has been recently emphasized. In this report, we investigated whether the naturally occurred sequence variations in the CXCL10 gene impact liver damage and disease progression of chronic HBV infection.
Methods：A hospital-based case-control study was conducted, and a total of 613 and 1787 unrelated Han Chinese HBV carriers were recruited from Beijing and Chongqing, respectively. We systematically screened sequence variations in the CXCL10 gene and examined the association between the variations in this gene and susceptibility to disease progression of chronic HBV infection in Chinese populations from Beijing and Chongqing . Functional analyses were conducted to verify the biological significances of the associated genetic variation.
Results：We identified that the polymorphism G-201A, located in the promoter region of CXCL10, was associated with susceptibility to disease progression in male HBV carriers (dominant model; odds ratio, 1.53; P.001). Functional analyses show that the G-201A polymorphism alters the binding affinity of nuclear protein and regulates CXCL10 expression. We observed higher CXCL10 transcription in interferon gamma–stimulated peripheral blood mononuclear cells with the diseasesusceptible genotypes. Enzyme-linked immunosorbent assay and immunohistochemical analysis showed augmented CXCL10 production in serum and liver tissues of progressed HBV carriers. Conclusions: The novel regulatory polymorphism G-201A in the promoter of CXCL10 gene could be a part of the genetic variation underlying the susceptibility of individuals to disease progression of chronic HBV infection. 
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