Department of Pharmacology, Toxicology & Therapeutics, University of Kansas Medical Center, Kansas City, KS, USA.
Liver Int. 2013 Aug;33(7):991-8. doi: 10.1111/liv.12148. Epub 2013 Mar 24.
BACKGROUND & AIMS: Both polymorphisms in the IL28B gene locus and ISG expression levels are associated with the outcome of hepatitis C virus (HCV) infection. The two are also interrelated, although the mechanism is unknown. Favourable CC genotype at rs12979860 expresses lower baseline ISG levels and responds better to treatment than unfavourable CT and TT genotypes. Little is known about this relationship in normal, uninfected liver. This study sought to explore this relationship.
Normal human liver specimens (64) and HCV positive human liver specimens (95) were genotyped for IL28B rs12979860 C > T. mRNA levels of ISGs and other relevant genes were studied by qPCR.
Most studied ISGs had significantly different expression by IL28B genotype in normal liver. CC genotype expressed the highest levels, CT intermediate and TT the lowest. This is opposite to the pattern seen in HCV patients. Principal component analysis of IL28B genotype and ISG expression further revealed a distinct set of genes correlated with the C allele (ISG15, HTATIP2, LGALS3BP, IRF2 and BCL2) and T allele (IFNα, β, γ, λ3 and CD80).
A subset of ISGs was found to be differentially expressed in normal liver by IL28B genotype. This suggests a relationship between IL28B genotype and gene expression before HCV infection.
IL28B 基因座的多态性和 ISG 表达水平均与丙型肝炎病毒(HCV)感染的结局相关。这两者也相互关联,尽管其机制尚不清楚。rs12979860 处有利的 CC 基因型表达较低的基线 ISG 水平,对治疗的反应优于不利的 CT 和 TT 基因型。在正常、未感染的肝脏中,对这种关系知之甚少。本研究旨在探讨这种关系。
对 64 例正常人类肝脏标本和 95 例 HCV 阳性人类肝脏标本进行 IL28B rs12979860 C > T 基因分型。通过 qPCR 研究 ISG 和其他相关基因的 mRNA 水平。
在正常肝脏中,大多数研究的 ISG 按 IL28B 基因型表达存在显著差异。CC 基因型表达水平最高,CT 基因型居中,TT 基因型最低。这与 HCV 患者的模式相反。IL28B 基因型和 ISG 表达的主成分分析进一步揭示了一组与 C 等位基因(ISG15、HTATIP2、LGALS3BP、IRF2 和 BCL2)和 T 等位基因(IFNα、β、γ、λ3 和 CD80)相关的独特基因。
发现一组 ISG 在正常肝脏中按 IL28B 基因型表达存在差异。这表明在 HCV 感染之前,IL28B 基因型与基因表达之间存在关系。