Association of gene expression involving innate immunity and genetic variation in IL28B with antiviral response

Innate immunity plays an important role in host antiviral response to hepatitis C viral （HCV） infection。最近，IL 28 B的单核苷多态性（SNP）和宿主响应到pegylated interferon·（PEG-IFN·）和ribavirin （RBV） were shown to be strongly associated。We aimed to determine the gene expression involving innate immunity in IL32B genotypes and elucidate its relation to response to antiviral treatment。我们用PEG-IFN·-2b/RBV和病毒传感器量化表达（RIG-I、MDA 5和LGP 2）、适配器分子（IPS-1）、相关泛素E3-配酶（RNF 125）、调制器（ISG 15和USP 18）和IL 28（IFN·）处理了88个慢性肝炎C患者的基因型IL 28 B SNP（rs 809917和rs 12979860）。两种IL 28 B SNPs均为100%唯一; 54名患者接受RS 809917 TT/RS 12979860 CC （IL 28 B主要患者）和34名RS 809917 TG/RS 12979860 CT （IL 28 B次要患者）。IL32B minor patients were significantly up-regulated compared with that in IL32B major patients （~3.3 fold， p<0.001）。However，IPS-1在IL 28 B小患者中明显较低（1.2折叠， p=0.028）。病毒传感器和调制器的Hepatic expressions of viral sensors and modulators were significantly higher in non-virological responders （NVR） than that in others despite stratification by IL 28 B genotype （~2）。6 fold， p<0.001）。多变量和ROC分析表明了RIG-I和ISG 15表达式和RIG-I/IPS-1表达式比是NVR的独立因素。Conclusion ： Gene expression involving innate immunity is strongly associated with IL32B genotype and response to PEG-IFN·/RBV。Both IL32B minor allele and higher RIG-land ISG15 expressions and RIG-I/IPS-1 ratio are independent factors for NVR。

Innate immunity plays an important role in host antiviral response to hepatitis C viral (HCV) infection. Recently, single nucleotide polymorphism (SNP) of IL28B and host response to pegylated interferon・(PEG-IFN・)and ribavirin (RBV) were shown to be strongly associated. We aimed to determine the gene expression involving innate immunity in IL28B genotypes and elucidate its relation to response to antiviral treatment. We genotyped IL28B SNPs (rs8099917 and rs12979860) in 88 chronic hepatitis C patients treated with PEG-IFN・-2b/RBV and quantified expressions of viral sensors (RIG-I, MDA5, and LGP2), adaptor molecule (IPS-1), related ubiquitin E3-ligase (RNF125), modulators (ISG15 and USP18), and IL28 (IFN・). Both IL28B SNPs were 100% identical ; 54 patients possessed rs8099917 TT/rs12979860 CC (IL28B major patients) and 34 possessed rs8099917 TG/rs12979860 CT (IL28B minor patients). Hepatic expressions of viral sensors and modulators in IL28B minor patients were significantly up-regulated compared with that in IL28B major patients (~3.3 fold, p<0.001). However, expression of IPS-1 was significantly lower in IL28B minor patients (1.2 fold, p=0.028). Hepatic expressions of viral sensors and modulators were significantly higher in non-virological responders (NVR) than that in others despite stratification by IL28B genotype (~2. 6 fold, p<0.001). Multivariate and ROC analyses indicated that higher RIG-I and ISG15 expressions and RIG-I/IPS-1 expression ratio were independent factors for NVR. Conclusion : Gene expression involving innate immunity is strongly associated with IL28B genotype and response to PEG-IFN・/RBV. Both IL28B minor allele and higher RIG-land ISG15 expressions and RIG-I/IPS-1 ratio are independent factors for NVR.