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Current status and prospects of studies on human genetic alleles associated with hepatitis B virus infection

机译：乙型肝炎病毒感染相关人类遗传等位基因的研究现状与展望

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摘要

Chronic hepatitis B virus (HBV) infection can cause a broad spectrum diseases, including from asymptomatic HBV carriers or cryptic hepatitis, to acute hepatitis, chronic hepatitis, Liver cirrhosis and primary hepatocellular carcinoma. The variable pattern and clinical outcome of the infection were mainly determined by virological itself factors, host immunological factors and genetic factors as well as the experimental factors. Among the human genetic factors, major candidate or identified genes involved in the process of HBV infection fall into the following categories: (1) genes that mediate the processes of viral entry into hepatocytes, including genes involved in viral binding, fusion with cellular membrane and transportation in target cells; (2) genes that modulate or control the immune response to HBV infection; (3) genes that participate in the pathological alterations in liver tissue; (4) genes involved in the development of liver cirrhosis and hepatocellular carcinoma associated with chronic HBV infection, including genes related to mother-to-infant transmission of HBV infection; and (5) those that contribute to resistance to antiviral therapies. Most of the reports of human genes associated with HBV infection have currently focused on HLA associations. For example, some investigators reported the association of the HLA class II alleles such as DRB1~*1302 or HLA-DR13 or DQA1~*0501-DQB1~*0301-DQB1~*1102 haplotypes with acute and/or chronic hepatitis B virus infection, respectively. Several pro-inflammatory cytokines such as Th1 cytokines (including IL-2 and IFIM-γ) and TNF-α have been identified to participate the process of viral clearance and host immune response to HBV. In contrast, the Th2 cytokine IL-10 serves as a potent inhibitor of Thl effector cells in HBV diseases. The MBP polymorphisms in its encoding region were found to be involved in chronic infection. Thus, reports from various laboratories have shown some inconsistencies with regard to the effects of host genetic factors on HBV clearance and persistence. Since genetic interactions are complex, it is unlikely that a single allelic variant is responsible for HBV resistance or susceptibility. However, the collective influence of several single nucleotide polymorphisms (SNPs) or haplotype (s) may underlie the natural combinational or synergistic protection against HBV. The future study including the multi-cohort collaboration will be needed to clarify these preliminary associations and identify other potential candidate genes. The ongoing study of the distributions and functions of the implicated allele polymorphisms will not only provide insight into the pathogenesis of HBV infection, but may also provide a novel rationale for new methods of diagnosis and therapeutic strategies.
机译：慢性乙型肝炎病毒（HBV）感染可引起多种疾病，包括从无症状HBV携带者或隐性肝炎到急性肝炎，慢性肝炎，肝硬化和原发性肝细胞癌。感染的可变模式和临床结果主要由病毒学本身因素，宿主免疫学因素，遗传因素以及实验因素决定。在人类遗传因素中，与HBV感染过程有关的主要候选基因或已鉴定的基因分为以下几类：（1）介导病毒进入肝细胞过程的基因，包括与病毒结合，与细胞膜融合和结合的基因。在靶细胞中运输； （2）调节或控制对HBV感染的免疫反应的基因； （3）参与肝脏组织病理改变的基因； （4）与慢性HBV感染有关的肝硬化和肝细胞癌发展相关基因，包括与HBV感染母婴传播有关的基因； （5）有助于抵抗抗病毒治疗的药物。与HBV感染有关的人类基因的大多数报道目前都集中在HLA关联上。例如，一些研究者报道了HLA II类等位基因，例如DRB1〜* 1302或HLA-DR13或DQA1〜* 0501-DQB1〜* 0301-DQB1〜* 1102单倍型与急性和/或慢性乙型肝炎病毒感染相关， 分别。已经确定了几种促炎性细胞因子，例如Th1细胞因子（包括IL-2和IFIM-γ）和TNF-α参与了病毒清除和宿主对HBV的免疫反应。相反，Th2细胞因子IL-10在HBV疾病中作为Th1效应细胞的有效抑制剂。发现其编码区的MBP多态性与慢性感染有关。因此，来自各个实验室的报告表明，在宿主遗传因素对HBV清除率和持久性的影响方面存在一些不一致之处。由于遗传相互作用是复杂的，因此单个等位基因变异不太可能导致HBV耐药性或易感性。但是，几种单核苷酸多态性（SNP）或单倍型的集体影响可能是针对HBV的天然组合或协同保护作用的基础。未来需要包括多队列研究在内的研究来阐明这些初步的关联并确定其他潜在的候选基因。正在进行的涉及等位基因多态性分布和功能的研究不仅将提供对HBV感染发病机制的洞察力，而且还将为诊断和治疗策略的新方法提供新的理论依据。

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  • 来源
    《World Journal of Gastroenterology》 |2003年第4期|p.641-644|共4页
  • 作者

    Fu-Sheng Wang;

  • 作者单位

    Division of Bioengineering, Beijing Institute of Infectious Diseases, 100 Xi Si-Huan-Zhong Road, Beijing 100039, China;

  • 收录信息 美国《科学引文索引》(SCI);美国《工程索引》(EI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 消化系及腹部疾病;
  • 关键词

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