Genetic Variation And Expression Of IL28B Are Associated With HCV And HBV Infection In Chinese Population

Hepatitis B and C are two infectious diseases in worldwide,which are the main reason of acute and chronic liver disease. HBV infection can cause a wide range of disease spectrum, including asymptomatic carriers, latent hepatitis, acute hepatitis, chronic hepatitis, fulminant hepatitis, and even cirrhosis, primary hepatocellular carcinoma. The hepatitis C virus (HCV) infection, approximately 20% -30% will clear the virus through spontaneous clearance, but 70% -80% will be persistent infection. In the course of antiviral treatment, the response to interferon therapy of HCV infection patients are very different, after Peg-interferon and ribavirin treatment, about 70% of the patients receive sustained virological response (SVR); while the remaining 30% of the patients showed no response to the treatment (No Response).After infected by both hepatitis viruses, there are diversity, different severity of disease, and different response to therapy. We have a common view that the virus, environment, race and clinical manifestations of patients may be related with diversity of disease, but it can not fully explain the real reason of the natural outcome of the disease. Present study shows that the host gene mutation is the most important factor. Especially in recent years, the results of research on host genetic polymorphisms and outcome of HCV infection continue to emerge, which have been reported, such as human leukocyte antigen, inflammatory chemokines, tumor necrosis factorα(TNF-α),interleukin and interferon stimulated genes,that gene polymorphisms related to HCV, HBV infection outcomes.It have confirmed the host genetic variation may lead to differences in the body immune function, further influencing different clinical outcomes of HBV, HCV infection.IL28B gene located on chromosome 19 interferon, consists of 6 exons, encoding IFN-λ3, as typeⅢ,are IFN-λs family. Recently Genome-wide Association Study(GWAS) of Africa, Europe population show that some single nucleotide polymorphisms near the IL28B coding IFNλ3 is related with spontaneous clearance capabilities of HCV viral and Response to interferon, so we speculated that the mutation and expression of IL28B gene may be associated closely with HCV, HBV infection.From the perspective of host genetic susceptibility, with the enlightenment from the latest international host of chronic hepatitis C gene polymorphism results, We studied the L28B rs12979860 polymorphism and its expression level in HBV and HCV patients respectively, meanwhile, some chronic HCV infection patients accepted antviral therapy. We collected blood samples of Jilin province among the Han population, including 896 subjects of hepatitis C (among of them,235 chronic HCV infection patients accepted treatment),156 subjects of hepatitis B.the selected population accorded with Hardy-Weinberg equilibrium, these IL28B SNP (rs12979860) polymorphism (C/T) were detected respectively through the pyrosequencing method. ELISA test was used for IL28B serum concentration; the Real Time PCR was applicated for mRNA expression of IL28 of peripheral blood mononuclear cells (PBMC). At the same time, we also analysised the response status of the 235 HCV infection patients after treatment.It was found that among populations of hepatitis C, the genotype frequency of rs12979860 CC of Chinese healthy population was 90.1%. C allele frequency (rs12979860) in spontaneous clearance group was higher than persistent infection patients (P=0.04). Maultivariate logistic regression analysis found, after adjusted gender and HBV infection, rs12979860 polymorphism is still an independent factor for HCV spontaneous clearance. Among patients carrying the C/C genotype, the rate of HCV spontaneous clearance are 2 times to T/C and T/T genotype patients (OR=2.13, P=0.04).Patients infected HCV genotype lb, HCV load of patients with C/C genotype was significantly higher than T/C or T/T genotype (P=0.014). Comparing with C/C genotype patients, the patients with T/C or T/T genotype had higher ALT level, and the difference was significant. We detected the serum and mRNA expression levels of IL28B and found that in the chronic HCV infection patients, serology and IL28B mRNA levels were significantly lower than the spontaneous group and the healthy control group. In IL28B rs12979860 C/C genotype group, serum levels and mRNA expression levels of IL28B were slightly higher than the population carrying T allele.In the course of IFN/RBV treatment for Chinese chronic HCV infection patients, the patients carrying C/C genotype of IL28B could produced higher virologic response rate, especially cEVR, and multivariate logistic regression analysis also confirmed that the IL28B polymorphism is an important predictor for chronic hepatitis C patients treatment.In the population infected hepatitis B, we detected a total of 156 HBV infected patients and healthy controls, testing serum levels and mRNA expression levels of IL28B in each groups, which found serum IL28B or mRNA expression of both groups(HBV carrier and healthy groups) were significantly higher than other groups (hepatitis, cirrhosis and liver cancer groups) (all P<0.05). Serum levels of IL28B of C/C genotype was higher than T/C genotype subjects (P<0.05). In the cirrhosis + hepatocellular carcinoma (HCC) patients, serum or IL28B mRNA levels with high aminotransferase (ALT/AST) of patient are significantly higher than patients with low transaminase levels (P<0.05)In summary, our research show that in the Chinese population, the rs12979860 SNP located IL28B upstream and the expression of IL28B is not only related with clinical outcomes of HCV infection and the response of antivirologic treatment, but also with the chronic HBV infection and disease progression. Further studies have shown that carrying the protective allele of IL28B can cause elevated expression levels of IL28B. both the mRNA level and serum levels of IL28B confirmed that host gene IL28B polymorphisms may directly affect its expression, whereas expression and function of IL28B may play a major role on the clinical outcome of the process in the HCV and HBV infection, In patients with high transaminase level and strong immune responses, IL28B may also actively participate in it. So we believe that in patients both with HCV or HBV infection of the Chinese population, IL28B SNP variations and the change of the expression level may be a beneficial factor to control HCV, HBV replication. Gene polymorphism of IL28B and its expression are inseparable from disease progression.