Expression and gene polymorphisms of interleukin 28B and hepatitis B virus infection in a Chinese Han population
Expression and gene polymorphisms of interleukin 28B and hepatitis B virus infection in a Chinese Han population
复制标题
中国汉族人群白细胞介素28B与乙型肝炎病毒感染的表达及基因多态性
DOI：
10.1111/j.1478-3231.2011.02507.x
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发表时间：
2011-09-01
影响因子：
6.7
通讯作者：
Niu, Junqi
中科院分区：
文献类型：
--
作者：
Li, Wanyu;Jiang, Yanfang;Niu, Junqi
背景资料：最近的全基因组关联研究发现，IL 28 B基因附近的遗传多态性与慢性感染丙型肝炎患者的持续病毒应答和自发病毒清除密切相关。目的：我们的目的是评估IL 28 B变异对中国汉族人群中B型肝炎病毒（HBV）感染的影响，并探讨IL 28 B多态性与感染易感性、病毒清除、疾病进展、病毒载量和肝脏炎症之间的关系。研究方法：我们在203例慢性HBV感染者、203例自限性HBV感染者和203例HBV血清标志物阴性者中检测了3种IL 28 B单基因多态性（rs12979860、rs12980275和rs8099917）。在所有受试者中评价白细胞介素（IL）28 B血清水平。此外，对42例慢性HBV感染者的外周血单个核细胞进行全基因组表达研究。结果：IL 28 B基因型、等位基因和单倍型频率与丙氨酸氨基转移酶水平和HBV DNA之间存在相关性。然而，慢性HBV感染者、自限性者和健康受试者的基因型或等位基因频率无显著差异。慢性HBV感染者血清IL 28 B水平低于自限性HBV感染者和健康人。血清IL 28 B水平与受试者的基因型相关。基因表达微阵列分析显示低HBV病毒载量患者IL 28 B表达增强。结论：IL 28 B位点的变异与HBV病毒载量和肝脏炎症相关。IL 28 B的遗传变异可能通过减少病毒载量和肝脏炎症来预防HBV进展，提供了一种有价值的基因治疗工具。
Background: Recent genome-wide association studies found that genetic polymorphisms near the IL28B gene is strongly associated with sustained viral response and spontaneous viral clearance in chronically infected hepatitis C patients. Aims: We aimed to evaluate the effects of IL28B variations on hepatitis B virus (HBV) infection in a Chinese Han population and to explore the association between IL28B polymorphisms and susceptibility to infection, viral clearance, disease progression, viral load and liver inflammation. Methods: We determined three IL28B single gene polymorphisms (rs12979860, rs12980275 and rs8099917) in 203 individuals with chronic HBV infection, 203 individuals with self-limited HBV infection and 203 individuals negative for all HBV seromarkers. Interleukin (IL) 28B serum levels were evaluated in all subjects. Additionally, peripheral blood mononuclear cells from 42 chronically HBV-infected individuals were subjected to whole-genome expression studies. Results: The association among genotype, allele and haplotype frequencies of IL28B with alanine aminotransferase levels and HBV DNA was established. However, no significant differences were observed in genotype or allele frequencies among chronically HBV-infected, self-limited and healthy subjects. The serum IL28B level was lower in patients with chronic HBV infection than in the self-limited HBV-infected or healthy subjects. The serum IL28B level was correlated with the subject's genotype. Gene expression micro-array analysis showed enhanced IL28B expression in patients with low HBV viral load. Conclusions: Variability at the IL28B locus is associated with HBV viral load and hepatic inflammation. Genetic variation of IL28B may prevent HBV progression by reducing viral load and liver inflammation, providing a valuable gene therapy tool.