IL28B Genetic Variation Is Associated with Spontaneous Clearance of Hepatitis C Virus, Treatment Response, Serum IL-28B Levels in Chinese Population

BackgroundThe interleukin-28B gene (IL28B) locus has been associated with host resistance to hepatitis C virus (HCV) infection and response to PEG-IFN/RBV treatment in western populations. This study was to determine whether this gene variant is also associated with spontaneous clearance of HCV infection, treatment response and IL-28B protein production in Chinese patients. MethodsWe genotyped IL28B genetic variations (rs12980275, rs8103142, rs8099917 and rs12979860) by pyrosequencing DNA samples from cohorts consisting of 529 subjects with persistent HCV infection, 196 subjects who cleared the infection, 171 healthy individuals and 235 chronic HCV patients underwent IFN/RBV treatment. The expression of IL-28B were measured by ELISA and RT-PCR. ResultsWe found that the four IL28B variants were in complete linkage disequilibrium (r2 = 0.97–0.98). The rs12979860 CC genotype was strongly associated with spontaneously HCV clearance and successful IFN/RBV treatment compared to the CT/TT. IL-28B levels in persistent HCV patients were significantly lower than subjects who spontaneously resolved HCV and healthy controls and were also associated with high levels of ALT (alanine aminotransferase) and AST (aspartate aminotransferase). IL-28B levels were also significantly lower in individuals carrying T alleles than CC homozygous. ConclusionsThus, the rs12979860-CC variant upstream of IL28B gene is associated with spontaneous clearance of HCV, susceptible to IFN/RBV treatment and increased IL-28B levels in this Chinese population.

研究背景：白细胞介素28B基因（interleukin-28B, IL28B）位点已被证实与西方人群宿主对丙型肝炎病毒（hepatitis C virus, HCV）感染的抵抗能力，以及聚乙二醇干扰素联合利巴韦林（PEG-IFN/RBV）治疗的应答效果相关。本研究旨在探究该基因变异在中国患者中是否同样与HCV感染自发清除、治疗应答及IL-28B蛋白表达相关。
研究方法：采用焦磷酸测序技术，对4个IL28B基因变异位点（rs12980275、rs8103142、rs8099917及rs12979860）进行基因分型。本研究队列共纳入529名慢性HCV持续感染者、196名自发清除HCV感染者、171名健康个体，以及235名接受IFN/RBV治疗的慢性HCV患者。通过酶联免疫吸附试验（ELISA）与逆转录聚合酶链反应（RT-PCR）检测IL-28B的表达水平。
研究结果：4个IL28B变异位点间呈现完全连锁不平衡（r²=0.97~0.98）。相较于CT/TT基因型，rs12979860 CC基因型与HCV自发清除及IFN/RBV治疗应答显著相关。慢性HCV持续感染者的IL-28B水平显著低于自发清除HCV者与健康对照，且IL-28B水平与丙氨酸氨基转移酶（alanine aminotransferase, ALT）、天冬氨酸氨基转移酶（aspartate aminotransferase, AST）水平呈正相关。携带T等位基因的个体IL-28B水平显著低于CC纯合子个体。
研究结论：综上，在中国人群中，IL28B基因上游的rs12979860-CC基因型与HCV感染自发清除、IFN/RBV治疗敏感性及IL-28B水平升高显著相关。