IL28B genotype effects during early treatment with peginterferon and ribavirin in difficult-to-treat hepatitis C virus infection.
IL28B genotype effects during early treatment with peginterferon and ribavirin in difficult-to-treat hepatitis C virus infection.
复制标题
DOI：
10.1093/infdis/jir264
复制
发表时间：
2011-08
期刊：
影响因子：
--
通讯作者：
John D. Scott;S. Holte;T. Urban;C. Burgess;E. Coppel;Chia Wang;L. Corey;J. Mchutchison;D. Goldstein
中科院分区：
文献类型：
--
作者：
John D. Scott;S. Holte;T. Urban;C. Burgess;E. Coppel;Chia Wang;L. Corey;J. Mchutchison;D. Goldstein
背景丙型肝炎病毒在治疗过程中的数学模型可以阐明抗病毒治疗的作用机制。在全基因组相关性研究中，IL28B基因多态对丙型肝炎病毒的治疗清除有很高的预测作用。方法收集20例慢性丙型肝炎患者治疗前28天13个时间点的血清。我们使用ABI TaqMan等位基因识别试剂盒评估了单核苷酸多态rs12979860处C等位基因的存在。我们使用丙型肝炎病毒感染的诺伊曼模型估计了整个人群的动态参数。重复非线性测量的统计方法通过建立响应预测因子来比较模型参数。结果IL28B基因频率分别为6(C/C)、11(C/T)和3(T/T)。与C/T或T/T基因携带者相比，C/C基因携带者在0-48小时内丙型肝炎病毒RNA的平均对数下降速度更快(1.4比0.7；P=0.07)，从2天到14天(1.6比0.7；P=0.04)。在多变量模型中，C/C基因型预测，在调整种族因素后，第二阶段的下降会更剧烈(P=0.01)。结论IL28B rs12979860的C/C基因可能通过增加感染肝细胞死亡率而发挥抗病毒作用。这表明，一种免疫介导的机制起到了作用。
BACKGROUND Mathematical models of hepatitis C virus (HCV) during therapy may elucidate mechanisms of action for antiviral therapy. In genome-wide association studies, IL28B gene polymorphisms are highly predictive of therapeutic clearance of HCV. METHODS We collected sera from 20 chronically infected HCV participants at 13 points during the first 28 days of therapy. We assessed the presence of the C allele at single-nucleotide polymorphism rs12979860 using the ABI TaqMan allelic discrimination kit. We estimated dynamic parameters from the entire population using the Neumann model for HCV infection. Statistical methods for repeated nonlinear measures compared model parameters by established predictors of response. RESULTS The frequencies of IL28B genotypes were 6 (C/C), 11 (C/T), and 3 (T/T). The mean log decline in HCV RNA from 0 to 48 hours was more rapid among C/C genotype participants compared with C/T or T/T genotype participants (1.4 vs 0.7; P = .07), and from 2 days to 14 days (1.6 vs 0.7; P = .04). In the multivariate model, the C/C genotype predicted a steeper second-phase decline when adjusted for race (P = .01). CONCLUSIONS The presence of the C/C genotype at IL28B rs12979860 exerts its antiviral effect by increasing the infected hepatocyte death rate. This suggests that an immune-mediated mechanism is responsible.