Liver Unit, Gastroenterology Service, Hospital Universitario de La Princesa, Instituto de Investigación Sanitario Princesa, Universidad Autónoma de Madrid, Madrid, Spain.
Clin Pharmacol Ther. 2011 Nov;90(5):712-21. doi: 10.1038/clpt.2011.189. Epub 2011 Oct 12.
Chronic hepatitis C (CHC) is a worldwide health problem that is highly related to liver fibrosis, cirrhosis, and hepatocellular carcinoma. The achievement of response to the current standard of care-pegylated interferon plus ribavirin-has recently been described to be associated with single-nucleotide polymorphisms (SNPs) near the IL-28B gene. Additionally, baseline expression levels of genes involved in interferon (IFN)-stimulated genes (ISGs) have been found to be related to treatment outcome. In the present study, 285 patients were genotyped for 63 SNPs within genes of the IFN signaling pathway (IPGs) and ISGs. Two ISG polymorphisms-OASL rs12819210 (odds ratio (OR)=2.1, P=0.03) and IFIT1 rs304478 (OR=2.5, P=0.01)-were found to be independent predictive factors of sustained virological response (SVR) after adjusting for other clinical covariates. Furthermore, the predictive value of IL-28B SNP was notably improved by simultaneous genotyping of rs12819210 and rs304478, particularly in patients with the worst prognosis (viral genotype 1, area under the curve (AUC)=0.74). In conclusion, ISG SNPs could constitute a valuable tool for individualizing CHC therapy.
慢性丙型肝炎（CHC）是一个全球性的健康问题，与肝纤维化、肝硬化和肝细胞癌高度相关。最近发现，对当前标准治疗-聚乙二醇干扰素加利巴韦林的反应与 IL-28B 基因附近的单核苷酸多态性（SNPs）有关。此外，干扰素（IFN）刺激基因（ISGs）相关基因的基线表达水平也与治疗结果有关。在本研究中，对 285 例患者进行了 IFN 信号通路（IPGs）和 ISGs 中 63 个 SNPs 的基因分型。两个 ISG 多态性-OASL rs12819210（比值比（OR）=2.1，P=0.03）和 IFIT1 rs304478（OR=2.5，P=0.01）-被发现是持续病毒学应答（SVR）的独立预测因素，在调整其他临床协变量后。此外，IL-28B SNP 的预测价值通过同时对 rs12819210 和 rs304478 进行基因分型得到显著改善，特别是在预后最差的患者中（病毒基因型 1，曲线下面积（AUC）=0.74）。总之，ISG SNPs 可以成为个体化 CHC 治疗的有价值的工具。
