الفهرس 
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Abstract
Hepatitis C virus (HCV) is the leading cause of liver cirrhosis and hepatocellular carcinoma (HCC). At present, there is no predictive biomarker for the patients at high risk of developing HCC.
In this study, we examined the association between single nucleotide polymorphisms (SNPs) in 3 innate immunity genes (OAS1 SNP rs10774671, IL-28B rs12979860, and LMP-7 at codon 49) besides CMV coinfection and susceptibility to HCC in genotype 4 (GT4) chronically infected Egyptian patients.
Interleukin-28B (IL-28B), named also as interferon λ-3, has been shown to be involved in the control of HCV infection, IL-28B has a role in the regulation of intracellular IFN stimulated gene (ISG) expression.
. IL-28B exhibits antiviral activity, having an impact on natural clearance of HCV, and the genetic polymorphism of the encoding IL-28B gene may determine the clearance of HCV,response to interferon treatment and progression of HCV to hepatocellular carcinoma.
OAS1 one of the most important ISGs encoding the antiviral enzyme 2_,5_-oligoadenylate synthetase (2_5_OAS) are critical components of the innate immune response to viruses. This enzyme uses adenosine triphosphate in 2_-specific nucleotidyl transfer reactions to synthesize 2_,5_-oligoadenylates, which activate latent ribonuclease, resulting in degradation of viral RNA and inhibition of virus replication.
Low molecular mass polypeptide 7 (LMP-7) gene is located on chromosome 6 inside the MHC class II region.
LMP-7 plays a essential role in MHC class I pathway by facilitating the processing and presentation of intracellular peptides to cytotoxic CD8 T cells thus enhancing the immune response to viral antigen.
Several studies have investigated the impact of LMP-7 polymorphisms on increased susceptibility to infectious diseases autoimmune disorders, and tumor development but there are not studies for relation between LMP-7 polymorphisms and progression of HCV to hepatocellular carcinoma.
Cytomegalovirus (CMV), a common virus, is one of the herpes viruses. Most people are exposed to CMV at some point during the course of their lives. Once CMV is in a person’s body, it stays there for the duration of his or her life.
SNPs were determined using restriction fragment length polymorphism (RFLP) analysis in DNA from HCC patients (n=34) and compared with either controls (n=70) or patients with early grades of liver fibrosis (n=49).
Our results demonstrated that patients bearing the genetic compound consisting of LMP-7 CA/AA (OR 4.75, 95% CI 1.443-15.631, p= 0.007) and IL-28B rs12979860 CT/TT (OR 6.00, 95% CI 1.603-22.455, p= 0.004) and positive for CMV viremia (OR 3.11, 95% CI 1.151- 8.412, p= 0.02) were more likely to have HCC. However, OAS1 SNP rs10774671 does not seem to contribute to the development of HCC. Binary regression analysis indicated that HCC risk significantly increases with the presence of each unfavorable genotype (LMP-7 CA/AA, IL-28B rs12979860 CT/TT) when accompanied by the existence of CMV coinfection (probability of HCC risk is 0.9 for combined factors versus 0.14, 0.07, 0.07 for individual factor IL-28B, LMP-7, and CMV; respectively).
These data suggest that the two SNPs and the coinfection in concert have potential in predicting the risk of HCC development in Egyptian patients infected with HCV GT4.