Department of Epidemiology and Biostatistics, School of Public Health, Nanjing Medical University, Nanjing 211166, China.
Department of Infectious Diseases, the People's Hospital of Jiangsu Province, Nanjing 210029, China.
Sci Rep. 2017 Feb 10;7:42408. doi: 10.1038/srep42408.
Recent many studies indicated a novel dinucleotide variant in ss469415590 (TT vs. ΔG) of interferon-λ 4 (IFNL4) gene strongly associated with hepatitis C virus clearance. To evaluate the impact and clinical usefulness of IFNL4 ss469415590 genotype on predicting both spontaneous HCV clearance and response to therapy in Chinese population, we genotyped 795 chronic HCV carriers, 460 subjects with HCV natural clearance and 362 patients with pegylated interferon-α and ribavirin (PEG IFN-α/RBV) treatment. IFNL4 ss469415590 variant genotypes significantly decreased host HCV clearance, both spontaneous (dominant model: OR = 0.50, 95% CI = 0.36-0.71) and IFN-α induced (dominant model: OR = 0.32, 95% CI = 0.18-0.56). Multivariate stepwise analysis indicated that ss469415590, rs12979860, the level of baseline HCV RNA and platelet were as independent predictors for sustained virological response (SVR). But the area under the ROC curve (AUC) was only 0.58 for ss469415590, and it was elevated to 0.71 by adding rs12979860, baseline HCV RNA and platelet in the prediction model of SVR. Therefore, these findings underscore that although genetic factors of host and pathogen were commonly important during HCV clearance, ss469415590 may be also a strongly predictive marker in the Chinese population.
最近的许多研究表明，干扰素-λ 4（IFNL4）基因中的新型二核苷酸变异 ss469415590（TT 对 ΔG）与丙型肝炎病毒清除强烈相关。为了评估 IFNL4 ss469415590 基因型对预测中国人群自发 HCV 清除和对治疗反应的影响和临床实用性，我们对 795 例慢性 HCV 携带者、460 例 HCV 自然清除者和 362 例聚乙二醇干扰素-α和利巴韦林（PEG IFN-α/RBV）治疗患者进行了基因分型。IFNL4 ss469415590 变异基因型显著降低了宿主 HCV 的清除率，无论是自发清除（显性模型：OR=0.50，95%CI=0.36-0.71）还是 IFN-α 诱导清除（显性模型：OR=0.32，95%CI=0.18-0.56）。多变量逐步分析表明，ss469415590、rs12979860、基线 HCV RNA 水平和血小板计数是持续病毒学应答（SVR）的独立预测因素。但是，ss469415590 的 ROC 曲线下面积（AUC）仅为 0.58，通过在 SVR 预测模型中添加 rs12979860、基线 HCV RNA 和血小板，AUC 升高至 0.71。因此，这些发现强调了尽管宿主和病原体的遗传因素在 HCV 清除过程中通常很重要，但 ss469415590 在中国人群中也可能是一个强有力的预测标志物。
