Li Dongling, Zheng Linghua, Jin Lei, Zhou Yuesu, Li Haiying, Fu Junliang, Shi Ming, Du Peishuang, Wang Lizhong, Wu Hao, Chen Guo-Yun, Zheng Pan, Liu Yang, Wang Fu-Sheng, Wang Shengdian
Center for Infection and Immunity, National Laboratory of Biomacromolecules, Institute of Biophysics, Beijing, China.
Hepatology. 2009 Sep;50(3):735-42. doi: 10.1002/hep.23047.
T-cell immunity to hepatitis B virus (HBV) is involved in both viral clearance and the pathogenesis of cirrhosis and hepatocellular carcinoma following chronic HBV infection. It is therefore of great interest to analyze whether genetic polymorphism of genes involved in the immune response may determine the outcomes of chronic HBV infection. Here we report that CD24 polymorphisms affect the risk and progression of chronic HBV infection. Thus the CD24 P170(T) allele, which is expressed at a higher level, is associated with an increased risk of chronic HBV infection. Among the chronic HBV patients this allele shows recessive association with more rapid progression to liver cirrhosis and hepatocellular carcinoma in comparison to the P170(C) allele. In contrast, a dinucleotide deletion at position 1527-1528 (P1527(del)), which reduces CD24 expression, is associated with a significantly reduced risk of chronic HBV infection. To confirm the role for CD24 in liver carcinogenesis, we compared the size of liver tumor developed in CD24(-/-) and CD24(+/-) HBV transgenic mice. Our data demonstrate that targeted mutation of CD24 drastically reduced the sizes of spontaneous liver cancer in the HBV transgenic mice.
These data demonstrate that genetic variation of CD24 may be an important determinant for the outcome of chronic HBV infection.
T细胞对乙型肝炎病毒（HBV）的免疫反应参与了慢性HBV感染后的病毒清除以及肝硬化和肝细胞癌的发病机制。因此，分析免疫反应相关基因的遗传多态性是否可能决定慢性HBV感染的结果具有重要意义。在此我们报告，CD24基因多态性影响慢性HBV感染的风险和进程。因此，表达水平较高的CD24 P170(T)等位基因与慢性HBV感染风险增加相关。在慢性HBV患者中，与P170(C)等位基因相比，该等位基因与更快进展至肝硬化和肝细胞癌呈隐性关联。相反，1527 - 1528位的二核苷酸缺失（P1527(del)）会降低CD24表达，与慢性HBV感染风险显著降低相关。为了证实CD24在肝癌发生中的作用，我们比较了CD24(-/-)和CD24(+/-) HBV转基因小鼠发生的肝肿瘤大小。我们的数据表明，CD24的靶向突变显著减小了HBV转基因小鼠自发性肝癌的大小。
这些数据表明，CD24的基因变异可能是慢性HBV感染结果的重要决定因素。
