Relation of HCV induced insulin resitance and Hepatocellular carcinoma: Role of MDR1 gene C.335t>C and C.3073A>C SNPS

Hepatocellular carcinoma (HCC), is the most common primary liver tumor. HCV-associated insulin resistance (IR) may cause hepatic steatosis, hepatic fibrosis and hepatocarcinogenesis. The multidrug resistance 1 gene (MDR1) is a candidate gene for susceptibility to HCC.. The aim of the current study was to evaluate the association of the MDR 1 gene c.335T>C and the c.3073A>C SNPs with HCV induced HCC and to correlate this toinsulin resistance state. A total of 205 HCC patients (on top of HCV) were enrolled in this study. Genotyping of MDR1 gene SNPs was done by PCR-RFLP.Results revealed that the association of genotypes/alleles from the c.335T.C and c.3073A.C SNPs with the risk of HCC. There was a significantly increased risk of HCC in chronic HCV that was associated with hepatic steatosis. The CC genotype of the c.335T>C polymorphism was associated with an increased risk of developing HCC compared to theTT genotype.It could be concluded from this work that HCV-related metabolic complications as hepatic steatosis and IR may be associatedwith increased risk of HCC development. c.335T>C and c.3073A>C SNPs of MDR1 gene could be considered as a possible molecular candidates for the HCC development in chronic HCV patients.Key words: HCV-HCC-Insulin Resistance -steatosis-MDR1genepolymorphis

Subchronic toxicity of propyl paraben IL-28B rs12979860 gene polymorphism as a predictor for hepatocellular carcinoma in Egyptian patients with chronic HCV genotype four

Hepatocellular carcinoma (HCC) is the fifth most common tumor worldwide. Hepatitis C virus (HCV) is largely responsible for the increase in incidence of HCC. There are few and controversial data available on the association between IL-28B single nucleotide polymorphisms (SNPs) and severity of liver fibrosis, presence of cirrhosis or developing HCC. So, the current study aimed to investigate the association between rs12979860 SNP of IL-28B gene and HCC in Egyptian patients infected with HCV genotype 4. Thishospital-based study included 150 patients with HCV infection that were classified into three groups: 50 patients with chronic hepatitis, 50 patients with cirrhosis, and 50 patients with hepatocellular carcinoma. The plasma Human interleukin 28B levels, liver enzymes activities and serum levels of total proteins, albumin, and fetoprotein were measured. Also, Genotyping of IL-28B rs12979860 C/T allele Polymorphism was carried out using RFLP-PCR. Fifty patients (33.3%) were CC homozygous genotype, whereas, the other 100 patients were either TT or CT. The genotype TT was more frequent in HCC group in comparison to chronic hepatitis group. In addition, Tcarriers increase significantly in HCC group than chronic hepatitis group. Also, IL-28B and -FP were significantly different in Tcarriersthan CC genotype, and in HCC patients in comparison to either chronic hepatitis or cirrhosis patients. In conclusion, this study suggests that in IL-28B rs12979860 C/T polymorphism, the T allele appears to be more prevalent in patients with end stage liver disease (liver cirrhosis and HCC). Furthermore, chronic HCV infection with end stage liver disease may be associated with a reduced IL-28B production. Further research is needed to reveal the cause-effect of these polymorphisms on host protective  immunity against HCV infection.Key words: IL-28B Gene Polymorphism-Hepatocellular carcinoma –chronic HC